E§§HNIKH HELLENIC ETAIPEIA SOCIETY OF ANO™O§O°IA™ IMMUNOLOGY ′
αTPIMHNIAIAνοσια EK¢O™H TH™ E§§HNIKH™ ETAIPEIA™ ANO™O§O°IA™ TOMO™ 5, TEYXO™ 1 ñ 2009
ISSN 1790-6490 anosia QUARTERLY EDITION OF THE HELLENIC SOCIETY OF IMMUNOLOGY VOLUME 5, NUMBER 1 ñ 2009 E§§HNIKH ETAIPEIA ANO™O§O°IA™
TPIMHNIAIA EK¢O™H ISSN 1790-6490 TOMO™ 5 ñ TEYXO™ 1 TH™ E§§HNIKH™ ETAIPEIA™ ANO™O§O°IA™ ª·È¿Ó‰ÚÔ˘ 23, 115 28 ∞ı‹Ó· | ΔËÏ. +30 210 7211845 | F·¯: +30 210 7215082 | ÂÚȯfiÌÂÓ· E-mail: [email protected] | http: //www.helsim.gr ¢IOIKHTIKO ™YMBOY§IO E.E.A. ¶Úfi‰ÚÔ˜ : X. NÈÎÔÏ¿Ô˘ AÓÙÈÚfi‰ÚÔ˜ : ¶. MÔ‡Ú· To ·ÚÂÏıfiÓ Î·È ÙÔ Ì¤ÏÏÔÓ Ù˘ ÂÈÛÙ‹Ì˘ Ù˘ ∞ÓÔÛÔÏÔÁ›·˜ °ÂÓ. °Ú·ÌÌ·Ù¤·˜ : A. TÛÈÚÔÁÈ¿ÓÓË Ã. ¡ÈÎÔÏ¿Ô˘ ...... 15 Eȉ. °Ú·ÌÌ·Ù¤·˜ : ¶. ™Î¤Ó‰ÚÔ˜ T·Ì›·˜ : X. ÕÓÙ˙Ô˘-AÁÁÔ˘Úȉ¿ÎË ∞ÓÔÛÔÏÔÁ›· Ù˘ Ïԛ̈͢ M¤ÏË : ª. μ¿ÚÏ·-§Â˘ıÂÚÈÒÙË ª. ™˘ÚÔÔ‡ÏÔ˘ Ã. ÕÓÙ˙Ô˘-∞ÁÁÔ˘Úȉ¿ÎË ...... 19 ™YNTAKTIKH E¶ITPO¶H ¶Úfi‰ÚÔ˜ : ¶. MÔ‡Ú· ÃÚfiÓȘ ÂÓ‰Ô΢ÙÙ¿ÚȘ ÏÔÈÌÒÍÂȘ: Y‡ı˘ÓÔÈ Û‡ÓÙ·Í˘ ÙÔ ·Ú¿‰ÂÈÁÌ· Ù˘ ‚ÚԢΤÏψÛ˘ X. NÈÎÔÏ¿Ô˘ ¶. ™Î¤Ó‰ÚÔ˜ ...... 22 º. ¶·ÏËÔÁÈ¿ÓÓË A. TÛÈÚÔÁÈ¿ÓÓË ∂Ì‚fiÏÈ·: ¶ÚÔ‚ÏËÌ·ÙÈÛÌÔ› Î·È ÚÔÔÙÈΤ˜ O. MˆÚ·ÏfiÁÏÔ˘-MÂÓ¤ÙÔ˘ X. ÕÓÙ˙Ô˘-AÁÁÔ˘Úȉ¿ÎË ª. ÷Ù˙ËÛÙ˘ÏÈ·ÓÔ‡-™È‰ËÚÔÔ‡ÏÔ˘ ...... 27 £. KÂÚ·ÌÈÙÛfiÁÏÔ˘ ∂ÈÛ·ÁˆÁ‹ ÛÙËÓ ·˘ÙÔ·ÓÔÛ›· ™YMBOY§EYTIKH E¶ITPO¶H † M. ¶·˘Ï¿ÙÔ˘ ∞. ™·Ú·ÓÙfiÔ˘ÏÔ˜ ...... 31 M. B¿ÚÏ·-§Â˘ıÂÚÈÒÙË °. B¤ÚÁÔ˘Ï·˜ ™˘ÛÙËÌ·ÙÈο ·˘ÙÔ¿ÓÔÛ· ÓÔÛ‹Ì·Ù·: ÙÔ ·Ú¿‰ÂÈÁÌ· Ù˘ ÚÂ˘Ì·ÙÔ- M. ¢·ÓÈËÏ›‰Ë˜ Âȉԇ˜ ·ıÚ›Ùȉ·˜ Î·È ÙÔ˘ Û˘ÛÙËÌ·ÙÈÎÔ‡ ÂÚ˘ıËÌ·ÙÒ‰Ô˘˜ χÎÔ˘ I. £ÂÔ‰ÒÚÔ˘ E. K·ÎÏ·Ì¿ÓË ∫. ΔÛ¤ÏÈÔ˜ ...... 35 º. K·Ó·ÎÔ‡‰Ë-T۷ηϛ‰Ô˘ °. K˘ÚÈ·˙‹˜ √ÚÁ·ÓÔÂȉÈο ·˘ÙÔ¿ÓÔÛ· ÓÔÛ‹Ì·Ù· A. M¿ÓıÔ˜ ∞. ΔÛÈÚÔÁÈ¿ÓÓË ...... 38 I. OÈÎÔÓÔÌ›‰Ô˘ X. ¶··ÛÙÂÚÈ¿‰Ë ∂ÚÁ·ÛÙËÚȷ΋ ÚÔÛ¤ÁÁÈÛË ·˘ÙÔ¿ÓÔÛˆÓ ÚÂ˘Ì·ÙÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ Z. ¶ÔÏ˘ÌÂÓ›‰Ë˜ M. P·ÙÔÔ‡ÏÔ˘-°ÈÁ‹ ∞ÈÎ. ¶·˘Ï›ÙÔ˘-ΔÛÈfiÓÙÛË ...... 43 AÈÎ. ™Ù·˘ÚÔÔ‡ÏÔ˘-°ÎÈfiη ™˘ÛÙËÌ·ÙÈο ·˘ÙÔÊÏÂÁÌÔÓÒ‰Ë ÓÔÛ‹Ì·Ù· E¶ITPO¶H E¶IME§EIA™ ™YNTA•H™ A. ™·Ú·ÓÙfiÔ˘ÏÔ˜ °. ªËÙÚÔ‡Ï˘, μ. ¶··‰fiÔ˘ÏÔ˜ ...... 49 ∫. ΔÛ¤ÏÈÔ˜ I. °ÎÔ˘ÁÎÔ˘Ú¤Ï·˜ ∞ÁÁÂȷ΋ ÊÏÂÁÌÔÓ‹ ÛÙËÓ ˘¤ÚÙ·ÛË Î·È ÙÔÓ Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË Y¶OBO§H AP£PøN-™YN¢POME™ ∫. ¶·Ï¤Ù·˜ ...... 57 °È· ÙÔ ÂÚÈÔ‰ÈÎfi ¶. ªÔ‡Ú· ∞Ó›¯Ó¢ÛË ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Ù˘ Ì˘ÔÛ›Ó˘ Û ·ÛıÂÓ›˜ ΔÌ‹Ì· ∫ÏÈÓÈ΋˜ ∞ÓÔÛÔÏÔÁ›·˜ μ′ ¶·ıÔÏÔÁÈ΋˜ ∫ÏÈÓÈ΋˜ ∞¶£ πÔÎÚ¿ÙÂÈÔ °.¶.N.£. | ∫ˆÓÛÙ·ÓÙÈÓÔ˘fiψ˜ 49 Ì ηÚΛÓÔ ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘ 546 42 £ÂÛÛ·ÏÔÓ›ÎË | TËÏ. 2310 892239 & 2310 992810 e-mail: [email protected] ∑. ¶·ÏÏ·ÓÙ˙¿, ª. ¡ÈÎÔÏÔÔ‡ÏÔ˘, ¡. ª¤ÌÔ˜, ∞. ∫·Ù¿ÎË, ° . ∫·Ú·ÓÙ˙›ÎÔ˜, EÙ‹ÛÈ· Û˘Ó‰ÚÔÌ‹ € 30,00 ¡. ∞ÏÂÍ·Ó‰ÚfiÔ˘ÏÔ˜, °. ¶·Ó¤ÙÛÔ˜, ª. ∫ˆÓÛÙ·ÓÙÔ˘Ï¿Î˘ ...... 63 Y¶EY£YNO™ TY¶O°PAºEIOY-¢IAºHMI™EøN UNIVERSITY STUDIO PRESS §ÂˆÓ›‰·˜ A. Mȯ¿Ï˘ AÚÌÂÓÔÔ‡ÏÔ˘ 32, 546 35 £ÂÛÛ·ÏÔÓ›ÎË TËÏ. 2310 209637, 2310 209837, Fax 2310 216647 ºˆÙÔÁÚ·Ê›· Â͈ʇÏÏÔ˘: ¶ÚÒÈÌÔ ÛÙ¿‰ÈÔ ·ÁÁÂȷ΋˜ ÊÏÂÁÌÔÓ‹˜ ÛÙÔÓ Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË. §ÂÌÊÔ΢ÙÙ·ÚÈ΋ E-mail: [email protected] ‰È‹ıËÛË ¯ˆÚ›˜ ·ÏÏÔ›ˆÛË ÙˆÓ ·ÁÁÂÈ·ÎÒÓ ÏÂÈÙÔ˘ÚÁÈÎÒÓ ·Ó·ÙÔÌÈÎÒÓ ÛÙÔȯ›ˆÓ. HELLENIC SOCIETY OF anosia IMMUNOLOGY TRIMESTRAL EDITION OF ISSN 1790-6490 VOLUME 5 NUMBER 1 THE HELLENIC SOCIETY OF IMMUNOLOGY ñ Meandrou 23, 115 28 Athens | Tel. + 30 210 7211845 | F·¯: + 30 210 7215082 | contents E-mail: [email protected] | http: //www.helsim.gr BOARD OF H.S.I. President : Ch. Nikolaou Vice President : P. Boura Past and future of Immunology General Secretary: A. Tsiroyianni Ch. ¡icolaou ...... 15 Specific Secretary: P. Skendros Treasurer : Ch. Antzou-Agouridaki Immunology of infections Members : M. Varla-Leftherioti M. Spiropoulou Ch. Antzou-Agouridaki ...... 19 EDITORIAL BOARD Editor in Chief : P. Boura Chronic intracellular infections: the paradigm of brucellosis Co-editors P. Skendros ...... 22 Ch. Nikolaou F. Palioyianni Vaccines: Arising questions and prospectives A. Tsiroyianni ª. Xatzistilianou-Sidiropoulou ...... 27 O. Moraloglou-Benetou Ch. Antzou-Agouridaki Introduction to Autoimmunity Th. Keramitsoglou ∞. Sarantopoulos ...... 31 ADVISORY COMMITTEE † M. Pavlatou Systemic Autoimmune diseases: The paradigm of Rheumatoid M. Daniilidis I. Ekonomidou Arthritis and Systemic Lupus Erythematosus E. Kaklamani ∫. Tselios ...... 35 F. Kanakoudi-Tsakalidou G. Kyriazis Organ specific autoimmune diseases A. Manthos Ch. Papasteriadi ∞. Δsirogianni ...... 38 Z. Polymenidis M. Raptopoulou-Gigi Laboratory approach of autoimmune diseases A. Stavropoulou-Gioka ∞ik. Pavlitou-TsiontsiÈ ...... 43 J. Theodorou M. Varla-Leftherioti Systemic autoinflammatory diseases G. Vergoulas EDITORIAL ASSISTANT COMMITTEE G. Mitroulis, V. Papadopoulos ...... 49 A. Sarantopoulos Vascular inflammation in hypertension and in diabetes K. Tselios J. Gougourelas ∫. Paletas ...... 57 SUBMISSION OF ARTICLES-SUBSCRIPTIONS anosia Autoimmune response against myosin in colorectal P. Boura, editor-in-chief cancer patients Clinical Immunology Unit, 2nd Medical Clinic, Hippokratio Gen. Hospital of Thessaloniki. |49 Konstantinoupoleos Str. ∑. Pallatza, M. Nikolopoulou, N. Memos, A. Kataki, G. Karantzikos, 546 42 Thessaloniki, Greece N. Alexandropoulos, G. Panetsos, M. Kostantoulakis ...... 63 TËÏ. +30 2310 892239 & +30 2310 992810 e-mail: [email protected] Annual subscription € 30,00 PUBLISHER UNIVERSITY STUDIO PRESS Leonidas A. Michalis Armenopoulou 32, 546 35 Thessaloniki Tel. 2310 209637, 2310 209837, Fax 2310 216647 E-mail: [email protected] E¶π™Δ∏ª√¡π∫∏ ∂∫¢∏§ø™∏ °π∞ Δ√¡ ∂√ƒΔ∞™ª√ Δ∏™ ¶∞°∫√™ªπ∞™ ∏ª∂ƒ∞™ ∞¡√™√§√°π∞™
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2009; 1: 15 – 18
∏ ·ÓÔÛÔÏÔÁ›· Â›Ó·È ¤Ó·˜ ıÂÌÂÏÈ҉˘ Î·È ÁÔËÙ¢ÙÈÎfi˜ Ù˜ ÂΛӘ ÎÔÈӈӛ˜, ›ÛÙ¢·Ó fiÙÈ ¿ÓıÚˆÔÈ Î·È Ê‡- ÎÏ¿‰Ô˜ Ù˘ È·ÙÚÈ΋˜. ∂›Ó·È Ë ÂÈÛÙ‹ÌË Ô˘ ·Û¯ÔÏÂ›Ù·È ÛË ÏÂÈÙÔ˘ÚÁÔ‡Ó Î¿Ùˆ ·fi ÙȘ Ì·ÁÈΤ˜ ÂÈÚÚÔ¤˜ Ó¢- Ì ÙË ÌÂϤÙË ÙˆÓ Ì˯·ÓÈÛÌÒÓ Ì ÙÔ˘˜ ÔÔ›Ô˘˜ Ô ÔÚ- Ì¿ÙˆÓ, ‰·ÈÌfiÓˆÓ ‹ ÙȘ Ì˘ÛÙÈΤ˜ ÂÈÚÚÔ¤˜ £ÂÒÓ. ™ÙËÓ Á·ÓÈÛÌfi˜ ·Ó·ÁÓˆÚ›˙ÂÈ, ÂÍÔ˘‰ÂÙÂÚÒÓÂÈ Î·È ·ÔÌ·ÎÚ‡- ·Ï·È¿ ‰È·ı‹ÎË, Ô £Âfi˜ ÛÙ¤ÏÓÂÈ ÏÔÈÌÔ‡˜ ˆ˜ ÙÈ̈ڛ· ÓÂÈ Î¿ı ͤÓÔ ÂÈÛ‚ÔϤ·. ªÔÓ·‰ÈÎfi ÔχÙÈÌÔ ÂÊfi‰ÈÔ Û ÂΛÓÔ˘˜ Ô˘ ÙÔÓ Î·Ù··ÙÔ‡Ó ·ÏÏ¿ Î·È ÛÙÔ˘˜ ¯- ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÂÈÛ‚ÔϤˆÓ, ıÚÔ‡˜ Ù˘ Ê˘Ï‹˜ ÙÔ˘ ¢·‚›‰, fiˆ˜ Â›Ó·È ÔÈ ∞ÈÁ‡ÙÈÔÈ, Â›Ó·È ÙÔ ·ÓÔÛÈ·Îfi Û‡ÛÙËÌ·, ¤Ó· Û‡ÛÙËÌ· ÔχÏÔÎÔ, ÔÈ ºÈÏÈÛÙ·›ÔÈ Î·È ÔÈ ∞ÛÛ‡ÚÈÔÈ. √È μ·‚˘ÏÒÓÈÔÈ Î·È ÔÈ ¿ÚÈÛÙ· ÔÚÁ·ÓˆÌ¤ÓÔ, ÚÔ˚fiÓ ÌÈ·˜ Ì·ÎÚ¿˜ ÂÍÂÏÈÎÙÈ΋˜ ∞ÈÁ‡ÙÈÔÈ ÁÈ· ÙËÓ ÚÔÛÙ·Û›· ÙÔ˘˜ ÂÚȤϷ‚·Ó ÛÙÔ ÔÚ›·˜, ÙÔ ÔÔ›Ô fiÛÔ Ë ¤Ú¢ӷ ÚÔ¯ˆÚ¿ÂÈ Ì·˜ «¶¿ÓıÂfi» ÙÔ˘˜ Î·È ¤Ó·Ó £Âfi ÁÈ· ÙȘ ·Ûı¤ÓÂȘ. ·ÔηχÙÂÙ·È ÔÏÔ¤Ó· Î·È ÂÚÈÛÛfiÙÂÚÔ Î·È Û˘Ó¯Ҙ √ ÈÛÙÔÚÈÎfi˜ £Ô˘Î˘‰›‰Ë˜, ÛÙÔÓ ·ÔÏÔÁÈÛÌfi ÙÔ˘ Ì·˜ ÂÎÏ‹ÛÛÂÈ Ì ÙȘ ·ÓÂÍ¿ÓÙÏËÙ˜ ‰˘Ó·ÙfiÙËÙ¤˜ ÙÔ˘. ÁÈ· ÙËÓ ·ÓÔ‡ÎÏ· Ù˘ ∞ı‹Ó·˜ ÙÔ 430 .Ã., ÂÚȤÁÚ·- ∏ ÈÛÙÔÚ›· Ù˘ ·ÓÔÛÔÏÔÁ›·˜ ·Ó¿ÁÂÙ·È ÛÙËÓ ·Ú- „ Ôχ ηϿ ÙÔ Ê·ÈÓfiÌÂÓÔ Ù˘ «Â·Ó·Ïԛ̈͢». ¯·ÈfiÙËÙ·. ∞fi ÙȘ ÚÔ˚ÛÙÔÚÈΤ˜ Áڷʤ˜ Á›ÓÂÙ·È Û·- √ £Ô˘Î˘‰›‰Ë˜ ‹Ù·Ó ¤Ó·˜ ·fi ·˘ÙÔ‡˜ Ô˘ ¤˙ËÛ·Ó Ê¤˜ fiÙÈ Ë ·ÓıÚˆfiÙËÙ· Ú¤ÂÈ Ó· ÁÓÒÚÈÛ ηٷ- Î·È ÊÚfiÓÙÈÛ·Ó ·ÚÚÒÛÙÔ˘˜ ¯ˆÚ›˜ ÙÔÓ Êfi‚Ô fiÙÈ ı· ÛÙÚÔʤ˜ ·fi ÂȉËÌÈΤ˜ ·Ûı¤ÓÂȘ, ·fi ÙËÓ ›‰È· ÙËÓ ÓÔÛ‹ÛÂÈ ¿ÏÈ. ∞˘Ù‹ Ë ·ÓÙ›ÛÙ·ÛË ÛÙËÓ Â·Ó·Ïԛ̈ÍË ¤Ó·ÚÍË Ù˘ ÎÔÈÓˆÓÈ΋˜ ÔÚÁ¿ÓˆÛ‹˜ Ù˘. ™ÙË ª¤ÌÊÈ- ÔÓÔÌ¿ÛıËΠimmunity ·fi ÙË Ï·ÙÈÓÈ΋ ϤÍË immu- ‰·, ÚˆÙÂ‡Ô˘Û· Ù˘ ·Ú¯·›·˜ ∞ÈÁ‡ÙÔ˘, Û ÌÈ· ¤- nitas Ô˘ ÛÙËÓ ·Ú¯·›· ƒÒÌË ÂÚȤÁÚ·Ê ÙËÓ ··Ï- ÙÚÈÓË Ï¿Î· ÙÔ˘ 3700 .Ã. Â›Ó·È ·ÔÙ˘ˆÌ¤ÓË Ë Ï·Á‹ ÂÓfi˜ ·ÙfiÌÔ˘ ·fi ÙȘ ˘Ô¯ÚÂÒÛÂȘ ÙÔ˘ ÛÙÔ ÚÒÙË ÂÈÎfiÓ· ÂÓfi˜ ı‡Ì·ÙÔ˜ Ù˘ ÔÏÈÔÌ˘ÂÏ›Ùȉ·˜, ÙÔ˘ ÎÚ¿ÙÔ˜ (ÊfiÚÔÈ, ÛÙÚ·ÙȈÙÈ΋ ıËÙ›·). ∂ÓÙÔ‡ÙÔȘ, ·˘Ùfi Ruma, ÙÔ˘ ÔÔ›Ô˘ Ë ÈÛÙÔÚ›· ÂÚÈÁÚ¿ÊÂÙ·È ÏÂÙÔÌÂ- ‰ÂÓ ·Ó·ÁÓˆÚ›ÛÙËΠÔÙ¤ ˆ˜ ÛÙÔÈ¯Â›Ô Î¿ÔÈÔ˘ ÂÛˆÙÂ- ÚÒ˜ Ì ÈÂÚÔÁÏ˘ÊÈ΋ ÁÚ·Ê‹. ™ÙË ªÂÛÔÔÙ·Ì›· (2000 ÚÈÎÔ‡ ·Ì˘ÓÙÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜, ̤¯ÚÈ Ù· Ù¤ÏË ÙÔ˘ 17Ô˘ .Ã.), Û ¤ÙÚÈÓË Ï¿Î· Ô˘ ·Ó·Ê¤ÚÂÙ·È ÛÙÔ ¤Ô˜ ·ÈÒÓ·. √ πÔÎÚ¿Ù˘ (460 .Ã. – 370 .Ã.) ‹Ù·Ó Ô ÙÔ˘ ‚·ÛÈÏÈ¿ Gilgamesh (Babylonian Epic of Gilga- ÚÒÙÔ˜ Ô˘ ·¤ÚÚÈ„Â ÙȘ ‰ÂÈÛȉ·ÈÌÔӛ˜ Î·È ¤ıÂÛ mesh), ‹Úˆ· Ù˘ ªÂÛÔÔÙ·Ì›·˜, ηٷÁÚ¿ÊÂÙ·È Ë ·- ÙËÓ ÂÔ›ıËÛË fiÙÈ Ë ·ÈÙ›· Ù˘ ·Ûı¤ÓÂÈ·˜ ‰ÂÓ ‹Ù·Ó ÌÈ· ÚÔ˘Û›· ÏÔÈÌÒÓ Î·È ·ÛıÂÓÂÈÒÓ. ΔËÓ ›‰È· ÂÔ¯‹ ÛÙËÓ ÙÈ̈ڛ· ·fi ÙÔÓ £Âfi, ·ÏÏ¿ ÚÔÎÏ‹ıËΠ·fi Ê˘ÛÈο ∞›Á˘ÙÔ Î·È ÛÙËÓ ∫›Ó·, Áڷʤ˜ ·Ó·Ê¤ÚÔ˘Ó fiÙÈ ÔÈ ¿Ó- ·›ÙÈ· (Û˘Ó‹ıÂȘ ‰È·ÙÚÔÊ‹˜ Î·È ‰È·‚›ˆÛË). Δ· ¤ÚÁ· ıÚˆÔÈ ÁÓÒÚÈ˙·Ó fiÙÈ ÂΛÓÔÈ Ô˘ ›¯·Ó ÂÈ˙‹ÛÂÈ ·fi ÙÔ˘, Ô˘ ·ÔÙÂÏÔ‡Ó ÙËÓ πÔÎÚ¿ÙÂÈÔ ™˘ÏÏÔÁ‹, Â›Ó·È ÌÈ· ·Ûı¤ÓÂÈ· ‰ÂÓ ÓÔÛÔ‡Û·Ó Í·Ó¿ ·fi ÙËÓ ›‰È· ·Ûı¤- 59 ÛÙÔÓ ·ÚÈıÌfi (ȈÓÈ΋ ‰È¿ÏÂÎÙÔ˜) Î·È Â›Ó·È Ù· ·Ú- ÓÂÈ·, ·ÏÏ¿ Î·È Â¿Ó ÓÔÛÔ‡Û·Ó ‰ÂÓ ¤ı·ÈÓ·Ó. ™ÙȘ ÚÒ- ¯·ÈfiÙÂÚ· ÌÓËÌ›· ·ÎÚÈ‚Ô‡˜ ÂÈÛÙËÌÔÓÈ΋˜ È·ÙÚÈ΋˜. 16 ΔÔ ·ÚÂÏıfiÓ Î·È ÙÔ Ì¤ÏÏÔÓ Ù˘ ÂÈÛÙ‹Ì˘ Ù˘ ∞ÓÔÛÔÏÔÁ›·˜
∏ ıˆڛ· ÙˆÓ ÊÈÏÔÛfiÊˆÓ Ù˘ ÂÔ¯‹˜ (400 .Ã.), ·ÔÎÙËı› ·ÓÔÛ›·, ¯ÔÚËÁ‹ıËΠÛÙÔ ·ÁfiÚÈ Ô Èfi˜ Ù˘ ∂̉ÔÎÏ‹, ¶Ï¿ÙˆÓ·, ∞ÚÈÛÙÔÙ¤ÏË, ·Ó·Ê¤ÚÂÈ fiÙÈ Ë Â˘ÏÔÁÈ¿˜ Smallpox ¯ˆÚ›˜ Ó· ÂÌÊ·ÓÈÛı› Ë ÓfiÛÔ˜. ∞˘- ʇÛË Û˘Ó›ÛÙ·Ù·È ·fi Ù¤ÛÛÂÚ· ÛÙÔȯ›·, °Ë, ¡ÂÚfi, Ù‹ Â›Ó·È Ë ÚÒÙË ·ÓÔÛÔÔ›ËÛË Î·È ÈÛÙÔÚÈο ·Ó‹ÎÂÈ ∞¤Ú· Î·È ºˆÙÈ¿, Î·È fiÙÈ Î¿ı Í¯ˆÚÈÛÙ‹ ÔÓÙfiÙËÙ· ÛÙÔÓ Edward Jenner6. ÛÙË Ê‡ÛË Û˘ÓÙ›ıÂÙ·È ·fi ÙÔÓ Û˘Ó‰˘·ÛÌfi ÙˆÓ 4 ·˘- ÙÒÓ ÛÙÔȯ›ˆÓ. √ πÔÎÚ¿Ù˘ ·ÓÙÈÛÙÔ›¯ËÛ ٷ 4 ·˘- μÚ·‚›· Nobel ÛÙËÓ ∞ÓÔÛÔÏÔÁ›· (The Nobel Ù¿ ÛÙÔȯ›·, Ì 4 ıÂÌÂÏÈÒ‰Ô˘˜ ÛËÌ·Û›·˜ ¯˘ÌÔ‡˜ ÙÔ˘ Prize in Physiology or Medicine) ÛÒÌ·ÙÔ˜ (ÊϤÁÌ·, ΛÙÚÈÓË ¯ÔÏ‹, Ì·‡ÚË ¯ÔÏ‹, ·›Ì·). ΔÔ fiÙÈ Ë ·ÓÔÛÔÏÔÁ›· ·ÔÙÂÏ› ¤Ó· Û˘Ó·Ú·ÛÙÈÎfi Â- ∞fi ÙËÓ ÈÛÔÚÚÔ›· ‹ ÙËÓ ·ÓÈÛÔÚÚÔ›· ÙˆÓ ¯˘ÌÒÓ ‰›Ô ¤Ú¢ӷ˜ Î·È ÂÊ·ÚÌÔÁ‹˜ ηٷ‰ÂÈÎÓ‡ÂÙ·È ·fi ÙoÓ ÂÍ·ÚÙ¿Ù·È Ë ˘Á›· ‹ Ë ÓfiÛÔ˜ (ıˆڛ· ÙˆÓ 4 ¯˘ÌÒÓ). ÛËÌ·ÓÙÈÎfi ·ÚÈıÌfi ‚Ú·‚›ˆÓ ¡fiÌÂÏ Ô˘ ·ÔÓÂÌ‹- ™˘ÓÂÎÙÈ΋ Ô˘Û›· ÙˆÓ ¿ÓÙˆÓ Â›Ó·È ÙÔ Ó‡̷. √ ªÈ- ıËÎ·Ó Û ÂÚ¢ÓËÙ¤˜ Ù˘: ıÚȉ¿Ù˘, Ô ÌÂÁ¿ÏÔ˜ ‚·ÛÈÏÈ¿˜ ÙÔ˘ ¶fiÓÙÔ˘, 80 .Ã., (¶¤ÚÛ˘ ÛÙËÓ Î·Ù·ÁˆÁ‹ Ô˘ ·Û¿ÛÙËΠÙËÓ ÂÏÏËÓÈ- 1901 Emil Adolf von Behring (1854-1917), University ΋ ÎÔ˘ÏÙÔ‡Ú· Î·È ÁÏÒÛÛ·), ÊÔ‚Ô‡ÌÂÓÔ˜ fiÙÈ ÔÈ ·ÓÙ›- Marburg, Germany ·ÏÔ› ÙÔ˘ ı· ÙÔÓ ÛÎfiÙˆÓ·Ó ¤·ÈÚÓ ‰ËÏËÙ‹ÚÈÔ Û ÌÈ- «ÁÈ· ÙËÓ ·Ó·Î¿Ï˘„Ë ÙÔ˘ ·ÓÙȉÈÊıÂÚÈÙÈÎÔ‡ ÔÚÔ‡» ÎÚ¤˜ ‰fiÛÂȘ, ÒÛÙ ӷ Û˘ÓËı›ÛÂÈ Ô ÔÚÁ·ÓÈÛÌfi˜ ÙÔ˘ 1905 Robert Koch (1843-1910), Institute for Infecti- (·ÓÔÛÔÔ›ËÛË) Ó· ·ÓÙȉڿ Û ÌÂÁ·Ï‡ÙÂÚ· ÔÛ¿. √È ous Diseases, Berlin, Germany ·Ú¯·›ÔÈ ∫ÈÓ¤˙ÔÈ, ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÂȉËÌ›·˜ «ÁÈ· ÙȘ ¤Ú¢Ó˜ Î·È ÙȘ ·Ó·Î·Ï‡„ÂȘ ÙÔ˘ Û ۯ¤ÛË Ì Ù˘ ¢ÏÔÁÈ¿˜ ·fi ÙÔ 1000 Ì.Ã., ηıÈ¤ÚˆÛ·Ó ÌÈ· ‰È·- ÙË Ê˘Ì·Ù›ˆÛË» ‰Èηۛ· ·ÛÎÒÓÙ·˜ ÌÈ· ÌÔÚÊ‹ ·ÓÔÛÔÔ›ËÛ˘ Ì ÙËÓ 1908 Ilya Ilyich Mechnikov (Russia, 1845-1916), Insti- ÂÈÛÓÔ‹ ÍËÚ‹˜ ÛÎfiÓ˘. ∏ ÛÎfiÓË ÚÔÂÚ¯fiÙ·Ó ·fi ÙȘ tut Pasteur Paris, France, Paul Ehrlich (France, 1854- ÎÚÔ‡ÛÙ˜ ÙˆÓ ÊÏ˘ÎÙ·ÈÓÒÓ Ù˘ ¢ÏÔÁÈ¿˜, Ù· ¿ÙÔÌ· ·˘- 1915), Goettingen University, Germany Ù¿ ‰ÂÓ ÓÔÛÔ‡Û·Ó ‹ ‰ÂÓ ÓÔÛÔ‡Û·Ó Ôχ ‚·ÚÈ¿ Î·È «ÁÈ· ÙËÓ ·Ó·ÁÓÒÚÈÛË ÙˆÓ ÂÚ¢ÓÒÓ ÙÔ˘˜ ÛÙËÓ ·ÓÔ- ‰ÂÓ ¤ı·ÈÓ·Ó. ∞ÚÁfiÙÂÚ· ÙÔÓ 15Ô ·ÈÒÓ·, Ë Ú·ÎÙÈ΋ Û›·» ÂÊ·ÚÌÔÁ‹˜ Ù˘ ÛÎfiÓ˘ ¿ÏÏ·ÍÂ Î·È Ì ÙË Ó‡ÍË ÌÈ·˜ 1913 Charles Robert Richet (1850-1935), Sorbonne ηÚÊ›ÙÛ·˜ Ë ÛÎfiÓË ‰È·ÂÚÓÔ‡Û ÙÔ ‰¤ÚÌ·. ∏ Ù¯ÓÈ- University, Paris, France ΋ ·˘Ù‹ ÔÓÔÌ¿ÛıËΠ“variolation” ·fi ÙÔ fiÓÔÌ· ÙÔ˘ «Û ·Ó·ÁÓÒÚÈÛË Ù˘ ÂÚÁ·Û›·˜ ÙÔ˘ ÁÈ· ÙËÓ ·Ó·Ê˘Ï·- ÌÔÏ˘ÛÌ·ÙÈÎÔ‡ ·Ú¿ÁÔÓÙ· (Èfi˜ variola). μ·ÛÈÎfi˜ ÛÎÔ- Í›·» fi˜ ÙÔ˘ “variolation” ‹Ù·Ó Ó· ÚÔηϤÛÂÈ ÛÎfiÈÌ· 1919 Jules Bordet (1870-1961), Brussels University, ÌÈ· ‹È· ÌfiÏ˘ÓÛË Ì ÙÔ ›‰ÈÔ ÙÔ ·ıÔÁfiÓÔ ¯ˆÚ›˜ ÙÚÔ- Belgium ÔÔÈ‹ÛÂȘ. √ ΛӉ˘ÓÔ˜ ı·Ó¿ÙÔ˘ ·fi ÙÔ “variolati- «ÂÚȤÁÚ·„ ÙËÓ ·ÈÌfiÏ˘ÛË Ô˘ ÚÔÎÏ‹ıËΠ·fi ÙËÓ on” ‹Ù·Ó ÂÚ›Ô˘ 2-3%, fï˜ ˘‹Ú¯Â ȉȷ›ÙÂÚË ‚ÂÏ- ¤ÎıÂÛË ÙÔ˘ ·›Ì·ÙÔ˜ Û ͤӷ ·ÙÙ·Ú· ·›Ì·ÙÔ˜» Ù›ˆÛË ÛÙÔ ÔÛÔÛÙfi ı·Ó¿ÙÔ˘ Û ۯ¤ÛË Ì ÙËÓ ·ÓÂ- 1930 Karl Landsteiner (Austria, 1868-1943), Rocke- ͤÏÂÁÎÙË ÌfiÏ˘ÓÛË. ∞˘Ù‹ Ë Ù¯ÓÈ΋ ÁÈ· ÙË ÌÂÙ¿‰ÔÛË feller Institute for Medical Research Ù˘ ¢ÏÔÁÈ¿˜, Ì ÌÔÚÊ‹ ÂÚÈÔÚÈṲ̂Ó˘ ÌfiÏ˘ÓÛ˘, «ÁÈ· ÙËÓ ·Ó·Î¿Ï˘„Ë ÙˆÓ ÔÌ¿‰ˆÓ ·›Ì·ÙÔ˜» ·fi ÙËÓ ∫›Ó· Ù·Í›‰Â„ ηٿ Ì‹ÎÔ˜ ÙˆÓ ·Ú·‰ÔÛÈ·- 1951 Max Theiler (Union of South Africa, 1899- ÎÒÓ ÂÌÔÚÈÎÒÓ ‰ÚfïÓ, ¤Ú·Û ·fi ÙË Ì¤ÛË ∞Ó·- 1972), Lab. Division of Medicine and Public Health, ÙÔÏ‹ Î·È ÙËÓ ∫ˆÓÛÙ·ÓÙÈÓÔ‡ÔÏË Î·È ‰È·‰fiıËΠ۠Rockefeller Foundation, NY, USA fiÏË ÙËÓ ∂˘ÚÒË1-5. «ÁÈ· ÙȘ ·Ó·Î·Ï‡„ÂȘ ÙÔ˘ Û¯ÂÙÈο Ì ÙÔÓ Î›ÙÚÈÓÔ ˘- ÚÂÙfi Î·È ÙËÓ Î·Ù·ÔϤÌËÛ‹ ÙÔ˘» Edward Jenner (vaccination), 1798 1957 Daniel Bovet (1907-1992), Istituto Superiore di To 1798 Ô ÕÁÁÏÔ˜ ·ıÔÏfiÁÔ˜ Edward Jenner ‰ËÌÔ- Sanità, Rome, Italy Û›Â˘Û ÌÈ· ÌÂϤÙË, Û‡Ìʈӷ Ì ÙËÓ ÔÔ›· ÔÈ ¿ÓıÚˆ- «ÁÈ· ÙȘ ·Ó·Î·Ï‡„ÂȘ ÙÔ˘ Û¯ÂÙÈο Ì ÙȘ Û˘ÓıÂÙÈΤ˜ ÔÈ ı· ÌÔÚÔ‡Û·Ó Ó· ÚÔÛٷ٢ıÔ‡Ó ·fi ÙËÓ Â˘- ÂÓÒÛÂȘ Ô˘ ÂÌÔ‰›˙Ô˘Ó ÙË ‰Ú¿ÛË ÔÚÈÛÌ¤ÓˆÓ Ô˘- ÏÔÁÈ¿ Â¿Ó ÙÔ˘˜ ÂÌ‚ÔÏ›·˙ (vaccination, vacca = ·ÁÂ- ÛÈÒÓ ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡, Î·È ÂȉÈο ÙË ‰Ú¿ÛË ÙÔ˘˜ ÛÙÔ Ï¿‰·) Ì ÙÔÓ Èfi Ù˘ ‰·Ì·Ï›Ùȉ·˜. ∂›¯Â ÚÔËÁËı› ÂÌ- ·ÁÁÂÈ·Îfi Û‡ÛÙËÌ· Î·È ÙÔ˘˜ ÛÎÂÏÂÙÈÎÔ‡˜ Ì˘˜» ‚ÔÏÈ·ÛÌfi˜ Û ¤Ó· ÌÈÎÚfi ·ÁfiÚÈ 8 ÂÙÒÓ (James Phipps) 1960 Sir Frank Macfarlane Burnet (1899-1985), Wal- Ì ÙÔÓ Èfi Ù˘ ‰·Ì·Ï›ÙȉԘ (cowpox) ·fi ÌÈ· ÂÚÁ¿- ter and Eliza Hall Inst. Med. Res. Melbourne, Australia, ÙÚÈ· Á·Ï·ÎÙÔÎÔÌ›Ԣ (Sarah Nelmes) Ô˘ ›¯Â ÌÔ- Peter Brian Medawar (1915-1987), University Colle- Ï˘Óı›. ªÂÙ¿ ¿ÚÔ‰Ô ÔÎÙÒ Â‚‰ÔÌ¿‰ˆÓ, ÒÛÙ ӷ ge, London, United Kingdom X. ¡ÈÎÔÏ¿Ô˘ 17
«ÁÈ· ÙËÓ ·Ó·Î¿Ï˘„Ë Ù˘ ›ÎÙËÙ˘ ·ÓÔÛÔÏÔÁÈ΋˜ nagel (Switzerland, 1944) University of Zurich, Insti- ·ÓÔ¯‹˜» tute of Experimental Immunology, Zurich, Switzer- 1972 Gerald M. Edelman (1929), Rockefeller land University New York, USA, Rodney R. Porter (1915- «ÁÈ· ÙȘ ·Ó·Î·Ï‡„ÂȘ ÙÔ˘˜ Û¯ÂÙÈο Ì ÙËÓ ÂȉÈÎfiÙËÙ· 1985), University of Oxford, United Kingdom Ù˘ ÌÂÛÔÏ·‚Ô‡ÌÂÓ˘ ·fi ·ÙÙ·Ú· ¿ÓÔÛ˘ ·¿ÓÙË- «ÁÈ· ÙȘ ·Ó·Î·Ï‡„ÂȘ ÙÔ˘˜ Û¯ÂÙÈο Ì ÙË ¯ËÌÈ΋ ‰Ô- Û˘» Ì‹ ÙˆÓ ·ÓÙÈۈ̿وӻ 1997 Stanley B. Prusiner, (1942), Univ. of California 1977 School of Medicine, San Francisco, CA, USA ·) Roger Guillemin (1924), The Salk Institute San «ÁÈ· ÙËÓ ·Ó·Î¿Ï˘„Ë ÙˆÓ Prions - ÌÈ· Ó¤· ‚ÈÔÏÔÁÈ΋ Diego, CA, USA, Andrew V. Schally (1926), Veterans ·Ú¯‹ Ù˘ Ïԛ̈͢» Administration Hospital, New Orleans, LA, USA 1999 Günter Blobel (USA) (1936), (in Waltersdorf/ «ÁÈ· ÙȘ ·Ó·Î·Ï‡„ÂȘ ÙÔ˘˜ Û¯ÂÙÈο Ì ÙËÓ ·Ú·ÁˆÁ‹ Silesia, Germany), Rockefeller University, New York, ÔÚÌÔÓÈÎÒÓ ÂÙȉ›ˆÓ ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘» NY, USA; Howard Hughes Medical Institute ‚) Rosalyn Yalow (1921), Veterans Administration «ÁÈ· ÙËÓ ·Ó·Î¿Ï˘„Ë fiÙÈ ÔÈ ÚˆÙ½Ó˜ ‰¤¯ÔÓÙ·È ÂÁÁÂ- Hospital, Bronx, NY, USA Ó‹ Û‹Ì·Ù· Ô˘ ηıÔ‰ËÁÔ‡Ó ÙË ÌÂÙ·ÊÔÚ¿ Î·È ÙËÓ ÙÔ- «ÁÈ· ÙËÓ ·Ó¿Ù˘ÍË Ú·‰ÈÔ·ÓÔÛÔÏÔÁÈÎÒÓ ÌÂıfi‰ˆÓ ÁÈ· Ôı¤ÙËÛ‹ ÙÔ˘˜ ÛÙÔ Î‡ÙÙ·ÚÔ»7 Ù· ÔÚÌÔÓÈο ÂÙ›‰È·» 2008 Francoise Barré-Sinoussi, Luc Montegnie. 1980 Baruj Benacerraf (1920), Harvard Medical «ÁÈ· ÙËÓ ·Ó·Î¿Ï˘„Ë ÙÔ˘ HIV». School Boston, MA, USA Jean Dausset (1916), Université de Paris, Lab. ∞ÓÔÛÔÏÔÁ›· – ÛÙfi¯ÔÈ ÁÈ· ÙÔ Ì¤ÏÏÔÓ Immuno-Hématologie, Paris, France George D. Snell (1903-1996), Jackson Laboratory ΔȘ ÙÂÏÂ˘Ù·›Â˜ ‰ÂηÂٛ˜ ‹Ïı ·ӿÛÙ·ÛË ÛÙËÓ Bar, Harbor, ME, USA ·ÓÔÛÔÏÔÁ›·, ‰fiıËÎ·Ó ··ÓÙ‹ÛÂȘ Û ÔÏÏ¿ ÂÚˆÙ‹- «ÁÈ· ÙȘ ·Ó·Î·Ï‡„ÂȘ ÙÔ˘˜ Û¯ÂÙÈο Ì ÙȘ ÁÂÓÂÙÈο η- Ì·Ù· Û¯ÂÙÈο Ì ÙË ‰È·ÌÂÛÔÏ·‚Ô‡ÌÂÓË ·fi ·ÙÙ·Ú· ıÔÚÈṲ̂Ó˜ ‰Ô̤˜ ÛÙËÓ ÂÈÊ¿ÓÂÈ· ΢ÙÙ¿ÚˆÓ Ô˘ ·ÓÔÛ›·, ÙÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜ Ô˘ Â›Ó·È ˘Â‡ı˘ÓÔÈ ÁÈ· Ú˘ıÌ›˙Ô˘Ó ÙȘ ·ÓÔÛÔÏÔÁÈΤ˜ ·ÓÙȉڿÛÂȘ» ÙËÓ ÔÈÎÈÏÔÌÔÚÊ›· ·ÓÙÈۈ̿وÓ, ηıÒ˜ ›Û˘ Î·È 1984 ÁÈ· Ù· ÌfiÚÈ· Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ·fi ÙÔ ‰›ÎÙ˘Ô ·) Niels K. Jerne (Denmark, 1911-1994), Basel Insti- ÙˆÓ ·ÓÔÛÔÏÔÁÈÎÒÓ Î˘ÙÙ¿ÚˆÓ ÁÈ· ÙË ÌÂٷ͇ ÙÔ˘˜ ÂÈ- tute for Immunology, Basel, Switzerland ÎÔÈÓˆÓ›·. ŸÌˆ˜ ·Ú·Ì¤ÓÔ˘Ó ÔÏÏ¿ ˙ËÙ‹Ì·Ù· Ô˘ «ÁÈ· ÙȘ ıˆڛ˜ ÙÔ˘ Û¯ÂÙÈο Ì ÙËÓ ÂȉÈÎfiÙËÙ· Î·È ÙËÓ Ú¤ÂÈ ·ÎfiÌË Ó· ÌÂÏÂÙËıÔ‡Ó ÒÛÙ ӷ ‰ÒÛÔ˘Ó Ï‡ÛÂȘ ÂͤÏÈÍË ÙÔ˘ ·ÓÔÛÔÔÈËÙÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜» Û ¯ÚfiÓÈ· Î·È ÛÔ‚·Ú¿ ÓÔÛ‹Ì·Ù· fiˆ˜ ÔÈ ÌÂÙ·ÌÔ- ‚) Georges J. F. Köhler (Germany, 1946-1995), Basel ۯ‡ÛÂȘ, Ë ·˘ÙÔ·ÓÔÛ›·, Ë ·ÏÏÂÚÁ›·, Ô Î·ÚΛÓÔ˜ , Institute for Immunology, Basel, Switzerland, César AIDS, ÂÎÊ˘ÏÈÛÙÈο ÓÔÛ‹Ì·Ù· ∫¡™: Milstein (Argentina, U.K., 1927-2002), MRC Labora- ªÂÙ·ÌÔۯ‡ÛÂȘ: ™‹ÌÂÚ· ÔÈ ÂÚ¢ÓËÙ¤˜ „¿- tory of Molecular Biology, Cambridge, ¯ÓÔ˘Ó ÙÚfiÔ˘˜ Ó· ÂÍ·Ï›„Ô˘Ó ÙÔ Úfi‚ÏËÌ· Ù˘ «ÁÈ· ÙËÓ ·Ó·Î¿Ï˘„Ë Ù˘ ·Ú¯‹˜ ÁÈ· ÙËÓ ·Ú·ÁˆÁ‹ ÙˆÓ ·ÓÔÛÔηٷÛÙÔÏ‹˜ ÛÙÚ¤ÊÔÓÙ·˜ ÙËÓ ÚÔÛÔ¯‹ ÙÔ˘˜: ÌÔÓÔÎψÓÈÎÒÓ ·ÓÙÈۈ̿وӻ ·) ÛÙÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜ Ù˘ ·ÓÔÛȷ΋˜ ·ÓÔ¯‹˜ ÒÛÙ ӷ 1987 Susumu Tonegawa, Japan (1936), Massachu- ÂÈÙ¢¯ı› Ë ·ÓÔ¯‹ ÙÔ˘ Ï‹ÙË ÛÙ· ͤӷ ·ÓÙÈÁfiÓ· ÙÔ˘ setts Institute of Technology (MIT), Cambridge, MA, ‰fiÙË, ‚) ÛÙÔ «¯ÈÌ·ÈÚÈÛÌfi» (chimerism), ÁÈ·ÙÚÔ› ÛÙȘ USAb ∏¶∞ ÂÚ¢ÓÔ‡Ó ¤Ó·Ó Ì˯·ÓÈÛÌfi Ô˘ ÂÈÙÚ¤ÂÈ ÌÂÙ¿ «ÁÈ· ÙËÓ ·Ó·Î¿Ï˘„‹ ÙÔ˘ Û¯ÂÙÈο Ì ÙË ÁÂÓÂÙÈ΋ ·Ú¯‹ ·fi ÚÔÂÙÔÈÌ·Û›· Ù· ͤӷ ·ÓÙÈÁfiÓ· ÙÔ˘ ‰fiÙË Ó· Á›- ÁÈ· ÙËÓ ·Ú·ÁˆÁ‹ Ù˘ ÔÈÎÈÏÔÌÔÚÊ›·˜ ·ÓÙÈۈ̿وӻ ÓÔÓÙ·È ·Ô‰ÂÎÙ¿ ·fi ÙÔÓ Ï‹ÙË, Á) ÛÙ· ·Ú¯¤ÁÔÓ· ÂÌ- 1990 Joseph E. Murray (1919), Brigham and Wo- ‚Ú˘˚ο ·ÙÙ·Ú·, Ô˘ Â›Ó·È ÔÈ ‚·ÛÈΤ˜ ‰ÔÌÈΤ˜ ÌÔÓ¿‰Â˜ men’s Hospital, Boston, MA, USA, E. Donnall Tho- Ù˘ ˙ˆ‹˜ Î·È Ô˘ ÌÔÚ› Ó· ÎÚ·ÙÔ‡Ó ÙÔ ÎÏÂȉ› ÁÈ· ÙÔ mas 1920 Fred Hutchinson Cancer Research Center, ̤ÏÏÔÓ Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘. Seattle, WA, USA ∞˘ÙÔ·ÓÔÛ›·: ™ÙËÓ ·˘ÙÔ·ÓÔÛ›·, ¤Ú· ·fi ÙË Û˘- «ÁÈ· ÙȘ ·Ó·Î·Ï‡„ÂȘ ÙÔ˘˜ Û¯ÂÙÈο Ì ÙË ÌÂÙ·Ìfi- ÛÙËÌ·ÙÈ΋ ηٷÛÙÔÏ‹ ÙˆÓ ÌÂÛÔÏ·‚ËÙÒÓ Ù˘ ÊÏÂÁÌÔ- Û¯Â˘ÛË ÔÚÁ¿ÓˆÓ Î·È Î˘ÙÙ¿ÚˆÓ ÛÙË ıÂڷ›· Ù˘ ·Ó- Ó‹˜, Á›ÓÔÓÙ·È ÚÔÛ¿ıÂȘ Ô˘ ‚·Û›˙ÔÓÙ·È ÛÂ Û˘ÁÎÂ- ıÚÒÈÓ˘ ·Ûı¤ÓÂÈ·˜» ÎÚÈ̤ÓË ·Ú¤Ì‚·ÛË Î·Ù¿ ÙˆÓ ·ıÔÁfiÓˆÓ Î˘ÙÙ¿ÚˆÓ 1996 Peter C. Doherty (Australia, 1940), St. Jude Ô˘ ÂÎÊÚ¿˙Ô˘Ó ÙÔ˘˜ ÌÂÛÔÏ·‚ËÙ¤˜ ÔÈ ÔÔ›ÔÈ ÚÔη- Child. Res. Hospital, Memphis, USA, Rolf M. Zinker- ÏÔ‡Ó ÙËÓ ·˘ÙÔ¿ÓÔÛË ÊÏÂÁÌÔÓ‹. ∫·Ù¿ Û˘Ó¤ÂÈ·, Ë 18 ΔÔ ·ÚÂÏıfiÓ Î·È ÙÔ Ì¤ÏÏÔÓ Ù˘ ÂÈÛÙ‹Ì˘ Ù˘ ∞ÓÔÛÔÏÔÁ›·˜
¿ÌÂÛË Î·È Û˘ÁÎÂÎÚÈ̤ÓË ıÂڷ›· ¤Ó·ÓÙÈ Î˘ÙÙ¿ÚˆÓ ∂ÎÊ˘ÏÈÛÙÈο ÓÔÛ‹Ì·Ù· – ‚Ï¿‚˜ ∫¡™: Δ· ÙÂÏ¢- ÛÙ· ÚÂ˘Ì·ÙÈο ÓÔÛ‹Ì·Ù· ı· ÚÔÛʤÚÂÈ Ú·ÁÌ·ÙÈο Ù·›· ¯ÚfiÓÈ· ÂӉȷʤÚÔÓÙ· ÂÈÚ·Ì·ÙÈο ·ÔÙÂϤÛÌ·- ıÂڷ¢ÙÈο ÏÂÔÓÂÎÙ‹Ì·Ù· ÛÙÔ Ì¤ÏÏÔÓ. Ù· ‰Â›¯ÓÔ˘Ó fiÙÈ Ù· ·Ú¯¤ÁÔÓ· ÂÌ‚Ú˘˚ο ·ÙÙ·Ú· ÌÂ- ∞ÏÏÂÚÁ›·: ™ÙËÓ ·ÏÏÂÚÁ›·, ‚·ÛÈÎfi ÚfiÏÔ ÛÙË ÌÂÏ- ÛÔÏ·‚Ô‡Ó ıÂڷ¢ÙÈο ÛÙË ÛÎÏ‹Ú˘ÓÛË Î·Ù¿ Ͽη˜. ÏÔÓÙÈ΋ ·ÓÙÈÌÂÙÒÈÛ‹ Ù˘ ı· ‰È·‰Ú·Ì·Ù›ÛÔ˘Ó ÔÈ ÛÙÔ- Δ· ·ÙÙ·Ú· ·˘Ù¿ ‰È·ÊÔÚÔÔÈÔ‡ÓÙ·È Û Ó¢ÚÒÓ˜ Î·È ¯Â˘Ì¤Ó˜ ıÂڷ›˜ ¤Ó·ÓÙÈ Û˘ÁÎÂÎÚÈÌ¤ÓˆÓ Î˘ÙÙ·ÚÔ- ÔÏÈÁÔ‰ÂÓ‰ÚÈÙÈο ·ÙÙ·Ú·, ÂÎÎÚ›ÓÔ˘Ó ·˘ÍËÙÈÎÔ‡˜ ·- ÎÈÓÒÓ, ¯ËÌÂÈÔÎÈÓÒÓ Î·È ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙÔ˘˜, ÔÈ ÔÔ›- Ú¿ÁÔÓÙ˜ Î·È ¤¯Ô˘Ó ·ÓÔÛÔÙÚÔÔÔÈËÙÈÎfi ÚfiÏÔ. ˜ Â›Ó·È ‰˘Ó·ÙfiÓ Ó· ÂÁ›ÚÔ˘Ó ÌÈ· ¿ÓÔÛË ·¿ÓÙËÛË Δ· ·Ú¯¤ÁÔÓ· ÂÌ‚Ú˘˚ο ·ÙÙ·Ú· ¯ÚËÛÈÌÔÔÈÔ‡- ÌË-·ÏÏÂÚÁÈ΋ Ì ÙËÓ ·ÚÂÌfi‰ÈÛË ‰È·‚›‚·Û˘ ÛËÌ¿- ÓÙ·È ÁÈ· ÙËÓ ·ÔηٿÛÙ·ÛË ‚Ï·‚ÒÓ ÙÔ˘ ÓˆÙÈ·›Ô˘ Ì˘Â- ÙˆÓ ÌÂٷ͇ ÙˆÓ ÌÔÚ›ˆÓ. ÏÔ‡. ∫·ÚΛÓÔ˜: ∞fi ηÈÚfi ·Ó·Ì¤ÓÂÙ·È fiÙÈ ı· ·Ó·- ∏ ·ÓÔÛÔÏÔÁ›· fiˆ˜ Ê·›ÓÂÙ·È Â›Ó·È ÌÈ· ÂÈÛÙ‹ÌË Ù˘¯ıÔ‡Ó ÂÌ‚fiÏÈ· ÁÈ· ÙË ¯Ú‹ÛË ÛÙË ıÂڷ›· ÙÔ˘ Ì ʈÙÂÈÓfi ̤ÏÏÔÓ, ˘fi ÙÔÓ fiÚÔ fiÙÈ ¤¯Ô˘Ì ÙË ı¤- ÚÔ¯ˆÚË̤ÓÔ˘ ηÚΛÓÔ˘ Î·È ÂȉÈÎfiÙÂÚ· Ù˘ ˘ÔÙÚÔ- ÏËÛË, ÙËÓ ˘ÔÌÔÓ‹ Î·È ÙË ‰ÈÔÚ·ÙÈÎfiÙËÙ· Ó· ·Û¯ÔÏË- ‹˜ ÙÔ˘ ηÚΛÓÔ˘ ÌÂÙ¿ ·fi ¯ÂÈÚÔ˘ÚÁÈ΋ ·Ê·›ÚÂÛË. ıԇ̠·ÔÙÂÏÂÛÌ·ÙÈο Ì ÙȘ ÚÔÎÏ‹ÛÂȘ Î·È Ó· ‰È·- Δ· ·ÔÙÂϤÛÌ·Ù· Ì ٷ ·˘ÙfiÏÔÁ· ÂÌ‚fiÏÈ· ΢ÙÙ¿ÚˆÓ ¯ÂÈÚÈÛÙԇ̠ÙȘ ¢ηÈڛ˜ Ô˘ Ë ÂÈÛÙ‹ÌË Ì·˜ ·- fiÁÎˆÓ ‰ÂÓ Â›Ó·È ÂÓı·ÚÚ˘ÓÙÈο. ∂ÓÙÔ‡ÙÔȘ, ÔÈ ÚfiÔ‰ÔÈ ÚÔ˘ÛÈ¿˙ÂÈ8. Ô˘ ¤ÁÈÓ·Ó ÛÙËÓ ÚÔËÁÔ‡ÌÂÓË ‰ÂηÂÙ›·, fiˆ˜ Ô Î·- ıÔÚÈÛÌfi˜ Ì ۷ʋÓÂÈ· ·ÓÙÈÁÔÓÈÎÒÓ ÌÔÚ›ˆÓ ÙÔ˘ fi- μÈ‚ÏÈÔÁÚ·Ê›· ÁÎÔ˘ ηıÒ˜ Î·È ÌÈ· ÛÂÈÚ¿ ÚˆÙÂ˚ÓÒÓ ÙÔ˘ fiÁÎÔ˘ Ô˘ ÙÒÚ· Â›Ó·È ‰È·ı¤ÛÈÌ·, ·Ú¿ÏÏËÏ· Ì ÙË ‚ÂÏÙ›ˆÛË Ù˘ 1. Silverstein AM. A history of immunology. New York: Aca- Ù¯ÓÔÏÔÁ›·˜ ÙˆÓ ÂÌ‚ÔÏ›ˆÓ Î·È ÙË ‰˘Ó·ÙfiÙËÙ· ÚÔÛ- demic Press, 1989. ‰ÈÔÚÈÛÌÔ‡ ÂȉÈÎÒÓ Δ-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ (tetramer), ‰›- 2. http://en.wikipedia.org./wiki/ timeline of immunology; Immu- ÓÔ˘Ó ÙËÓ ÚÔÔÙÈ΋ ÁÈ· ÌÈ· Ó¤· ÁÂÓÈ¿ ÂÌ‚ÔÏ›ˆÓ ηٿ nology History IV. ÙÔ˘ ηÚΛÓÔ˘. 3. http//www.keratin.com/am/am004.shtml/ Stewart Sell and AIDS: °È· ÙÔ AIDS, ·Ú¿ ÙȘ ·ÔÙ˘¯Ë̤Ó˜ Scotti.Rodkey, Ashort history of immunology. ÚÔÛ¿ıÂȘ ÁÈ· ÙËÓ ·Ó¿Ù˘ÍË ÂÓfi˜ ·ÔÙÂÏÂÛÌ·ÙÈ- 4. http://en.wikipedia.org./wiki/ ancient greek medicin. ÎÔ‡ ÂÌ‚ÔÏ›Ô˘ Ô˘ ı· ÂÍÔ˘‰ÂÙÂÚÒÓÂÈ ÙÔÓ Èfi, Û‹ÌÂÚ· 5. http://en.wikipedia.org./wiki/ inoculation. ˘¿Ú¯ÂÈ ÌÈ· Û˘ÁÎÚ·ÙË̤ÓË ·ÈÛÈÔ‰ÔÍ›· ÁÈ· ¤Ó· ÂÌ‚fi- 6. http://en.wikipedia.org./wiki/ancienten.wikipedia.org./wiki/ ÏÈÔ Ô˘ ı· ÚÔÏ·Ì‚¿ÓÂÈ ÙË ÌfiÏ˘ÓÛË Û ÌÂÚÈÎÔ‡˜ Edward.Jenner. ·ÛıÂÓ›˜ Î·È Ë ÓfiÛÔ˜ ı· ¤¯ÂÈ ·ÚÁ‹ ÂͤÏÈÍË. ∏ ‰ËÌÈ- 7. http//www.studyoverseas.com/uk/uked/immune.htm. Ô˘ÚÁ›· ÂÓfi˜ ÂÌ‚ÔÏ›Ô˘ Ô˘ ı· ÂÈÙ‡¯ÂÈ ÙËÓ ·Ó¿Ù˘ÍË 8. http//www. Immunology.klimov,tom.ru/1-2.php. ÂÓfi˜ Â˘Ú¤Ô˜ Ê¿ÛÌ·ÙÔ˜ ÂÍÔ˘‰ÂÙÂÚˆÙÈÎÒÓ ·ÓÙÈۈ̿- ÙˆÓ ¤Ó·ÓÙÈ ÙÔ˘ HIV Â›Ó·È ¤Ó·˜ ÂÏȉÔÊfiÚÔ˜ ÛÙfi¯Ô˜ ∞ÏÏËÏÔÁÚ·Ê›·: Ù˘ ÌÂÏÏÔÓÙÈ΋˜ ¤Ú¢ӷ˜. E-mail: [email protected] AÓÔÛÔÏÔÁ›· Ïԛ̈͢
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2009; 1: 19 – 21
√ ·ÓıÚÒÈÓÔ˜ ÔÚÁ·ÓÈÛÌfi˜ Â›Ó·È ÛÙ·ıÂÚ¿ ÂÎÙÂıÂÈ̤- ÚÔ˘ Á·ÛÙÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ ‰ËÌÈÔ˘ÚÁÔ‡Ó ·ÔÙÂÏÂ- ÓÔ˜ Û ÌÈÎÚÔÔÚÁ·ÓÈÛÌÔ‡˜ Ì ÙÔ˘˜ ÔÔ›Ô˘˜ ¤Ú¯ÂÙ·È ÛÌ·ÙÈÎfi ÊÚ·ÁÌfi ÛÙË Ïԛ̈ÍË. ηıËÌÂÚÈÓ¿ Û ·ʋ. ∏ Ïԛ̈ÍË fï˜ ¤گÂÙ·È Ìfi- Á) ªÈÎÚÔ‚È·ÎÔ‡˜: ∏ ÌÈÎÚԂȷ΋ ¯ÏˆÚ›‰· ÙÔ˘ ÓÔ Î¿Ùˆ ·fi ÔÚÈṲ̂Ó˜ ÚÔ¸Ôı¤ÛÂȘ, ηıÒ˜ Ô ÔÚ- ÛÒÌ·ÙÔ˜ ·›˙ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÚÔÛÙ·Û›·˜ ·ÓÙ·- Á·ÓÈÛÌfi˜ ÚÔÛٷهÂÙ·È ·fi ÙÔ ·ÓÔÛÈ·Îfi Ì·˜ Û‡ÛÙË- ÁˆÓÈ˙fiÌÂÓË Ù· ¿ÏÏ· ·ıÔÁfiÓ· ˆ˜ ÚÔ˜ ÙËÓ ÙÚÔÊ‹, Ì·. Δo ‰¤ÚÌ· Â›Ó·È ÂÓÂÚÁfi ̤ÚÔ˜ ÙÔ˘ ·ÓÔÛÈ·ÎÔ‡ Û˘- ÂÓÒ Â›Ó·È Èı·ÓfiÓ Ó· ¤¯Ô˘Ó Î·È ·ÓÙÈ‚·ÎÙËÚÈ·ÎÔ‡˜ ·- ÛÙ‹Ì·ÙÔ˜ Î·È ·ÔÙÂÏ› ÙÔÓ ÚÒÙÔ Ê˘ÛÈÎfi ÊÚ·ÁÌfi. Ú¿ÁÔÓÙ˜, fiˆ˜, .¯., E. Coli Ô˘ ÂÎÎÚ›ÓÂÈ ÎÔÏÈÛ›Ó˜ ∞ÎÔÏÔ˘ıÔ‡Ó Ù· ·ÙÙ·Ú· Ù˘ ÚÒÙ˘ ÁÚ·ÌÌ‹˜ ¿Ì˘Ó·˜ Ô˘ ·ÔÙÚ¤Ô˘Ó ÙÔÓ ·ÔÈÎÈÛÌfi ¿ÏÏˆÓ ·ıÔÁfiÓˆÓ1. ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ Ô˘ ·ÔÙÂÏÔ‡Ó ÙË Ê˘ÛÈ΋ ‹ ¤ÌÊ˘ÙË °È· Ó· ‰È·ÂÚ¿ÛÂÈ ÙÔ ·ıÔÁfiÓÔ ÙËÓ ÂÈıËÏȷ΋ ·ÓÔÛ›· Î·È ·Ó ÍÂʇÁÔ˘Ó Ù· ·ıÔÁfiÓ· ·fi ·˘Ù‹ ÙË ÛÙÔÈ‚¿‰· Ú¤ÂÈ Ó· ˘¿Ú¯ÂÈ Ï‡ÛË Ù˘ Û˘Ó¤¯ÂÈ·˜ ÙÔ˘ ÛÂÈÚ¿ ¿Ì˘Ó·˜ ˘¿Ú¯ÂÈ Î·È Ë ÙÚ›ÙË ÁÚ·ÌÌ‹ ¿Ì˘Ó·˜, Ù· ‰¤ÚÌ·ÙÔ˜ fiˆ˜ Û˘Ì‚·›ÓÂÈ Û ÙÚ·‡Ì·Ù· ‹ ÂÁη‡Ì·Ù·. ·ÙÙ·Ú· Ù˘ ÂȉÈ΋˜ ‹ ›ÎÙËÙ˘ ·ÓÔÛ›·˜. Δ· ·ÙÙ·Ú· ∂¿Ó Î·È fiÙ·Ó Û˘Ì‚Â› ·˘Ùfi ı· Ú¤ÂÈ Ó· ·ÓÙÈÌÂÙˆ›ÛÂÈ Ù˘ ÂȉÈ΋˜ ·ÓÔÛ›·˜ ÛÙÔ¯Â‡Ô˘Ó ÛÂ Û˘ÁÎÂÎÚÈ̤ÓÔ ·- Ù· ·ÙÙ·Ú· Ù˘ Ê˘ÛÈ΋˜ ¿Ì˘Ó·˜ (Ô˘‰ÂÙÂÚfiÊÈÏ·, ˈ- ıÔÁfiÓÔ, ‰ËÌÈÔ˘ÚÁÔ‡Ó ·ÓÙÈÛÒÌ·Ù· Î·È Î‡ÙÙ·Ú· ÌÓ‹- ÛÈÓfiÊÈÏ·, ¡∫, ÌÔÓÔ‡ÚËÓ·) Ù· ÔÔ›· ÛÙÚ·ÙÔÏÔÁÔ‡- Ì˘ Ù· ÔÔ›· ı· ÚÔÛٷ٤„Ô˘Ó ÙÔÓ ÔÚÁ·ÓÈÛÌfi ·fi ÓÙ·È ¿ÌÂÛ·, ̤۷ Û 4 ÒÚ˜ ·fi ÙËÓ Â›ÛÔ‰Ô ÙÔ˘ ·- ÌÈ· ÌÂÙ¤ÂÈÙ· Ïԛ̈ÍË ·fi ÙÔ ›‰ÈÔ ·ıÔÁfiÓÔ. ıÔÁfiÓÔ˘1. º˘ÛÈÎfi˜ ÊÚ·ÁÌfi˜: ∞ÔÙÂÏÂ›Ù·È ·fi Ù· ÂÈıË- ŸÏ· Ù· ·ÙÙ·Ú· Ù˘ Ê˘ÛÈ΋˜ Î·È ÂȉÈ΋˜ ·ÓÔ- Ïȷο ·ÙÙ·Ú· Ô˘ ηχÙÔ˘Ó fiÏË ÙËÓ ÂÈÊ¿ÓÂÈ· ÙÔ˘ Û›·˜ Ô˘ ÚÔÛÙ·ÙÂ‡Ô˘Ó ÙÔÓ ÔÚÁ·ÓÈÛÌfi ·Ì˘ÓfiÌÂÓ· ‰¤ÚÌ·ÙÔ˜ Î·È fiϘ ÙȘ ÂÈÊ¿ÓÂȘ ÙˆÓ ÛˆÏËÓˆ‰ÒÓ ¤Ó·ÓÙÈ ÙÔ˘ οı ÌÈÎÚÔ‚›Ô˘ ÔÓÔÌ¿˙ÔÓÙ·È ·ÓÔÛÔ˚ηӿ ‰ÔÌÒÓ fiˆ˜ Ô Á·ÛÙÚÂÓÙÂÚÈÎfi˜ ۈϋӷ˜, ÙÔ ·Ó·- ·ÙÙ·Ú·. ¶·Ú¿ÁÔÓÙ·È ÛÙÔÓ Ì˘ÂÏfi ÙˆÓ ÔÛÙÒÓ ·fi ¤- Ó¢ÛÙÈÎfi Û‡ÛÙËÌ· Î·È Ô Ô˘ÚÔÁÂÓÓËÙÈÎfi˜ ۈϋӷ˜. Ó· ÔÏ˘‰‡Ó·ÌÔ ·Ú¯¤ÁÔÓÔ ·ÈÌÔÔÈËÙÈÎfi ·ÙÙ·ÚÔ √ Ê˘ÛÈÎfi˜ ÊÚ·ÁÌfi˜ ·Ì‡ÓÂÙ·È Ì ÌÈ· ÔÈÎÈÏ›· Ì˯·- (Stem cell). ∞fi ·˘Ùfi ÙÔ Î‡ÙÙ·ÚÔ ı· ÚÔ¤ÏıÔ˘Ó ÓÈÛÌÒÓ: ÚÔÁÂÓÓ‹ÙÔÚ˜ ÁÈ· ÙËÓ ÂÚ˘ıÚ¿ ÛÂÈÚ¿, ÙË ÛÂÈÚ¿ ÙˆÓ ·) ªË¯·ÓÈÎÔ‡˜: Δ· ÂÈıËÏȷο ·ÙÙ·Ú· ¤¯Ô˘Ó ·ÈÌÔÂÙ·Ï›ˆÓ Î·È ÁÈ· ÙȘ ‰˘Ô ‚·ÛÈΤ˜ ÛÂÈÚ¤˜ ÙˆÓ Ï¢- ÛÙÂÓ¤˜ ‰È·Û˘Ó‰¤ÛÂȘ ÌÂٷ͇ ÙÔ˘˜ Ô˘ ‰ÂÓ ÂÈÙÚ¤- ÎÒÓ, ‰ËÏ·‰‹ ÙË ÛÂÈÚ¿ ÙˆÓ ÔÏ˘ÌÔÚÊÔ‡ÚËÓˆÓ, ÙˆÓ Ô˘Ó ÙËÓ Â›ÛÔ‰Ô ÙˆÓ ÌÈÎÚÔ‚›ˆÓ. ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ Î·È ÙˆÓ ÌÔÓÔ‡ÚËÓˆÓ. Δ· ÔÏ˘ÌÔÚ- ‚) ÃËÌÈÎÔ‡˜: ∂›Ó·È Ù· ÏÈ·Ú¿ Ôͤ· ÙÔ˘ ‰¤ÚÌ·- ÊÔ‡ÚËÓ· ÔÓÔÌ¿˙ÔÓÙ·È ¤ÙÛÈ ÏfiÁˆ ÙÔ˘ ÔχÌÔÚÊÔ˘ ÙÔ˜ Î·È ¤Ó˙˘Ì· fiˆ˜ Ë Ï˘ÛÔ˙‡ÌË, Ë ÔÔ›· ˘¿Ú¯ÂÈ ˘Ú‹Ó· ‹ ÎÔÎÎÈÔ·ÙÙ·Ú· ÏfiÁˆ ÙˆÓ ÎÔÎΛˆÓ Ô˘ Â- Û ‰È¿ÊÔÚ· ˘ÁÚ¿ (‰¿ÎÚ˘·, Û¿ÏÈÔ, ȉÚÒÙ·˜), ÙÔ fiÍÈÓÔ ÚȤ¯ÔÓÙ·È ÛÙÔ Î˘ÙÙ·ÚfiÏ·ÛÌ·. Èڛ˙ÔÓÙ·È Û Ԣ‰Â- PH ÙÔ˘ ÛÙÔÌ¿¯Ô˘ Î·È Ù· ÂÙÈο ¤Ó˙˘Ì· ÙÔ˘ ·ÓˆÙ¤- ÙÂÚfiÊÈÏ·, ˈÛÈÓfiÊÈÏ· Î·È ‚·ÛÂfiÊÈÏ·. Δ· Ô˘‰ÂÙÂÚfi- 20 ∞ÓÔÛÔÏÔÁ›· Ù˘ Ïԛ̈͢
ÊÈÏ· Â›Ó·È Ù· ϤÔÓ ÔÏ˘¿ÚÈıÌ· ·ÙÙ·Ú· Î·È ·ÔÙÂ- ¯ÚfiÓÔ˜ ··Ú·›ÙËÙÔ˜ ÁÈ· ÙË ‰ËÌÈÔ˘ÚÁ›· ÙˆÓ ·ÓÙÈÛˆ- ÏÔ‡Ó ÙÔ 65-70% ÙˆÓ Î˘ÙÙ¿ÚˆÓ Ô˘ ΢ÎÏÔÊÔÚÔ‡Ó Ì¿ÙˆÓ. Δ· ·ÓÙÈÛÒÌ·Ù· Ù¿Í˘ IgG Ô˘ ΢ÎÏÔÊÔÚÔ‡Ó ÛÙÔ ·›Ì·. ∂›Ó·È ‚Ú·¯‡‚È·, ˙Ô˘Ó 3-5 ̤Ú˜ Î·È Â›Ó·È ÂÈοıÔÓÙ·È ÛÙËÓ ÂÈÊ¿ÓÂÈ· ÙˆÓ ÌÈÎÚÔ‚›ˆÓ Ì ˘Ô- ·˘Ù¿ Ô˘ ·ÔÙÂÏÔ‡Ó ÙËÓ ÚÒÙË ÛÂÈÚ¿ ¿Ì˘Ó·˜ ηıÒ˜ ‰Ô¯Â›˜ ΢ڛˆ˜ Fc Î·È Î·Ù¿ ·˘ÙfiÓ ÙÔÓ ÙÚfiÔ ·Ó·ÁÓˆ- Â›Ó·È ÈÛ¯˘Ú¿ ‚·ÎÙËÚÈÔÊ¿Á·2. Ú›˙ÔÓÙ·È ·fi ÙÔ˘˜ ·ÓÙ›ÛÙÔÈ¯Ô˘˜ ÁÈ· Fc ˘Ô‰Ô¯Â›˜ ÙˆÓ Δ· ˈÛÈÓfiÊÈÏ· ·ÔÙÂÏÔ‡Ó ÙÔ 2-5% ÙˆÓ Î˘ÎÏÔ- Ê·ÁÔ΢ÙÙ¿ÚˆÓ. ∏ ‰È·‰Èηۛ· Ù˘ Ê·ÁÔ΢ÙÙ¿ÚˆÛ˘, ÊÔÚÔ‡ÓÙˆÓ Î˘ÙÙ¿ÚˆÓ Î·È ·Ó·Ù‡ÛÛÔÓÙ·È Û ·Ú·ÛÈ- Ô˘ ÛÙËÓ Ô˘Û›· ·ÔÙÂÏ› Ï‹ÚË ·Ô‰fiÌËÛË ÙÔ˘ ÌÈ- ÙÈΤ˜ ÏÔÈÌÒÍÂȘ Î·È ·ÏÏÂÚÁÈΤ˜ ηٷÛÙ¿ÛÂȘ. Δ· ‚·ÛÂ- ÎÚÔ‚›Ô˘ Î·È ·Ô‚ÔÏ‹ ÙÔ˘ ·fi ÙÔ Î˘ÙÙ·ÚfiÏ·ÛÌ·, Á›- fiÊÈÏ· ÚÔηÏÔ‡Ó ÙÔÈÎfi Ô›‰ËÌ· ÏfiÁˆ Ù˘ ¤ÎÎÚÈÛ˘ ÓÂÙ·È Û ÂÚÈıˆÚÈÔÔÈË̤ÓÔ Ì¤ÚÔ˜ ÙÔ˘ ΢ÙÙ·ÚÔÏ¿- ÈÛÙ·Ì›Ó˘. Δ· ÌÔÓÔ‡ÚËÓ· ·ÔÙÂÏÔ‡Ó ÙÔ 3-4% ÙˆÓ ÛÌ·ÙÔ˜, ÛÙÔ Ê·Áfiۈ̷ Î·È ÛÙÔ Ê·ÁÔÏ˘Ûfiۈ̷. ∏ ΢ÎÏÔÊÔÚÔ‡ÓÙˆÓ Î˘ÙÙ¿ÚˆÓ. ∑Ô˘Ó ÛÙËÓ Î˘ÎÏÔÊÔÚ›· ηٷÛÙÚÔÊ‹ ÔÊ›ÏÂÙ·È ÛÙ· ÎÔÎΛ· Ô˘ ˘¿Ú¯Ô˘Ó ÛÙÔ 72 ÒÚ˜ Î·È ÂÈÛÂÚ¯fiÌÂÓ· ÛÙÔ˘˜ ÈÛÙÔ‡˜ ÌÂÙ·ÙÚ¤Ô- ΢ÙÙ·ÚfiÏ·ÛÌ·, Ù· ÔÔ›· ÂÚȤ¯Ô˘Ó ‰Ú·ÛÙÈΤ˜ Ô˘Û›Â˜ ÓÙ·È Û ̷ÎÚÔÊ¿Á·. §fiÁˆ Ù˘ ÌÂÁ¿Ï˘ Ê·ÁÔ΢ÙÙ·ÚÈ- fiˆ˜, Ì˘ÂÏÔ¸ÂÚÔÍÂȉ¿ÛË, Ï˘ÛÔ˙‡ÌË, ÚˆÙÂÔÏ˘ÙÈο ΋˜ ÈηÓfiÙËÙ¿˜ ÙÔ˘˜ ÔÓÔÌ¿˙ÔÓÙ·È Â·ÁÁÂÏ̷ٛ˜ Ê·- ¤Ó˙˘Ì·, ηÙÈÔÓÈΤ˜ ÚˆÙ½Ӥ˜ ÎÏ. ∏ fiÏË ‰È·‰Èηۛ·, ÁÔ·ÙÙ·Ú·. ∏ Ê·ÁÔ΢ÙÙ¿ÚˆÛË ·ÎÔÏÔ˘ı› Ù· ÂÍ‹˜ ÏfiÁˆ Ù˘ ÌÂÁ¿Ï˘ ηٷӿψÛ˘ Ô͢ÁfiÓÔ˘, ÔÓÔÌ¿˙Â- ÛÙ¿‰È·3: Ù·È ·Ó·Ó¢ÛÙÈ΋ ¤ÎÚËÍË. Δ· ‰Â ÚÔ˚fiÓÙ· Ô˘ ·Ú¿- ™ÙËÓ ·Ú¯‹ ‰È·ÎÚ›ÓÔ˘Ì ÙË ¯ËÌÂÈÔÙ·Í›· Ô˘ Â›Ó·È ÁÔÓÙ·È Â›Ó·È ÙÔÍÈΤ˜ Ô˘Û›Â˜ Ô˘ ÔÓÔÌ¿˙ÔÓÙ·È ROIs ‹ Ë ÌÂÙ·Ó¿ÛÙ¢ÛË ÙˆÓ Î‡ÙÙ·ÚˆÓ ·fi ÙÔ ·›Ì· ÛÙÔ ÛË- ¡√πs ·Ó¿ÏÔÁ· ·Ó Â›Ó·È ÚÔ˚fiÓÙ· Ô͢ÁfiÓÔ˘ ‹ ·˙ÒÙÔ˘. ÌÂ›Ô Ù˘ ÊÏÂÁÌÔÓ‹˜. ∞˘Ùfi ÂÈÙ˘Á¯¿ÓÂÙ·È Ì ÙÔ˘˜ ŸÏ˜ ·˘Ù¤˜ ÔÈ ÙÔÍÈΤ˜ Ô˘Û›Â˜ Â›Ó·È ÂχıÂÚ˜ Ú›˙˜ 4 ˘Ô‰Ô¯Â›˜ Ô˘ ˘¿Ú¯Ô˘Ó ÛÙËÓ ÂÈÊ¿ÓÂÈ· ÙˆÓ Î˘ÙÙ¿- Ô͢ÁfiÓÔ˘, ·˙ÒÙÔ˘ (NO H2O2) . ÚˆÓ Î·È ÔÈ ÔÔ›ÔÈ ‰¤¯ÔÓÙ·È Î·È ·Ó·ÁÓˆÚ›˙Ô˘Ó ÌËÓ‡- Δ· Ì·ÎÚÔÊ¿Á· ÂÎÙfi˜ ·fi ÙÔ Ó· Â›Ó·È Â·ÁÁÂÏ- Ì·Ù· ·fi ÙÔ ÛËÌÂ›Ô Ù˘ ÊÏÂÁÌÔÓ‹˜, fiˆ˜ ηÙÂ- ̷ٛ˜ Ê·ÁÔ·ÙÙ·Ú· Â›Ó·È Ú˘ıÌÈÛÙ¤˜ Ù˘ ¿Ì˘Ó·˜, ‰Èfi- ÛÙÚ·Ì̤ӷ ÌÈÎÚfi‚È·, ·ÙÙ·Ú·, ¯ËÌÂÈÔΛÓ˜, ΢ÙÙ·ÚÔ- ÙÈ fiÙ·Ó ÂÓÂÚÁÔÔÈÔ‡ÓÙ·È ÂÎÎÚ›ÓÔ˘Ó Î˘ÙÙ·ÚÔΛÓ˜. √È Î›Ó˜. ∏ ÂÍ·ÁÁ›ˆÛË Î·È Ë ÌÂÙ·Ó¿ÛÙ¢ÛË ÙˆÓ Î˘ÙÙ¿- ΢ÙÙ·ÚÔΛÓ˜ Ì ÙË ÛÂÈÚ¿ ÙÔ˘˜ ÂÓÂÚÁÔÔÈÔ‡Ó ¿ÏÏ· ÚˆÓ ÛÙÔ ÛËÌÂ›Ô Ù˘ ÊÏÂÁÌÔÓ‹˜ Á›ÓÂÙ·È Ì ÙË Û˘ÌÌÂ- ·ÙÙ·Ú· Î·È ÂÈÙ›ÓÔ˘Ó ÙË Ê·ÁÔ΢ÙÙ¿ÚˆÛË Î·È ÙËÓ ÙÔ¯‹ ÙˆÓ ÌÔÚ›ˆÓ ÚÔÛÎfiÏÏËÛ˘ (adhesion molecu- ¿Ì˘Ó· ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡. √È Î˘ÙÙ·ÚÔΛÓ˜ ·›˙Ô˘Ó Î˘- les). Δ· ÌfiÚÈ· ·˘Ù¿ ·ÔÙÂÏÔ‡Ó Ù· ÂÙ›‰È· Ù˘ ΢Ù- Ú›·Ú¯Ô ÚfiÏÔ ÛÙËÓ ¿Ì˘Ó· ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡, Û˘ÌÌÂÙ¤- Ù·ÚÈ΋˜ ÂÈÊ¿ÓÂÈ·˜ Î·È ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÙȘ ÔÈÎÔÁ¤ÓÂÈ- ¯ÔÓÙ·˜ ¿ÌÂÛ· ‹ ¤ÌÌÂÛ· Û ÔÈΛϘ ΢ÙÙ·ÚÈΤ˜ ·ÓÙÈ- ˜ ÙˆÓ ÛÂÏÂÎÙÈÓÒÓ, ÈÓÙÂÁÎÚ›Ó˜, ÙËÓ ˘ÂÚ-ÔÈÎÔÁ¤ÓÂÈ· ‰Ú¿ÛÂȘ, Ú˘ıÌ›˙ÔÓÙ·˜ Î·È Î·Ù¢ı‡ÓÔÓÙ·˜ ÙËÓ ÔÚ›· ÙˆÓ ·ÓÔÛÔÛÊ·ÈÚÈÓÒÓ Î·ıÒ˜ Î·È ÙȘ ·ÓÙÚÂÛ›Ó˜ (ad- Î·È ÙËÓ ¤Î‚·ÛË Ù˘ ·ÓÔÛȷ΋˜ ·¿ÓÙËÛ˘. Δ· ÌÔÓÔ- dressins). ∞ÎÔÏÔ˘ı› Ë ·Ó·ÁÓÒÚÈÛË, Ë ÔÔ›· ÂÈÙ˘Á- ‡ÚËÓ· Ê·ÁÔ·ÙÙ·Ú· ÂÎÎÚ›ÓÔ˘Ó IL1, IL6, TNF· Î.Ï.., ¯¿ÓÂÙ·È Â›Û˘ Ì ÙÔ˘˜ ˘Ô‰Ô¯Â›˜ ÂÈÊ·Ó›·˜ Ô˘ Ô˘Û›Â˜ Ô˘ ·˘Í¿ÓÔ˘Ó ÙÔÓ ÔÏÏ·Ï·ÛÈ·ÛÌfi, ÂÓÂÚÁÔ- ˘¿Ú¯Ô˘Ó ¿ÊıÔÓÔÈ ¿Óˆ ÛÙ· Ê·ÁÔ·ÙÙ·Ú· Î·È ÔÈ ÔÈÔ‡Ó ‹ ·Ó·ÛÙ¤ÏÏÔ˘Ó ÌÈ· ·ÓÙ›‰Ú·ÛË. ∏ IL6 ÚÔ¿ÁÂÈ ÔÔ›ÔÈ ·Ó·ÁÓˆÚ›˙Ô˘Ó ÎÔÈÓ¿ Û˘ÛÙ·ÙÈο ÔÏÏÒÓ ‚·ÎÙË- ÙËÓ ¤ÎÎÚÈÛË Ù˘ IL2, Ô˘ Ô‰ËÁ› ÛÙÔÓ ÔÏÏ·Ï·ÛÈ·- ÚÈ·ÎÒÓ ÂÈÊ·ÓÂÈÒÓ (PAMPs – Pathogen-associated ÛÌfi ÙˆÓ Δ-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ. molecular patterns). ™ËÌ·ÓÙÈÎfi˜ ˘Ô‰Ô¯¤·˜ Ô˘ ˘- ŒÓ·˜ ¿ÏÏÔ˜ ÛËÌ·ÓÙÈÎfi˜ Ì˯·ÓÈÛÌfi˜ ÙˆÓ Ì·- ¿Ú¯ÂÈ Û fiÏ· Ù· ·ÙÙ·Ú· Â›Ó·È ÙÔ CD14 Ô˘ ·Ó·- ÎÚÔÊ¿ÁˆÓ Â›Ó·È Ë ·ÓÙÈÁÔÓÔ-·ÚÔ˘Û›·ÛË, ηıÒ˜ Ù· ÁÓˆÚ›˙ÂÈ ÙÔ˘˜ ÏÈÔÔÏ˘Û·Î¯·Ú›Ù˜ ÙˆÓ ÌÈÎÚÔ‚›ˆÓ. ·ÓÙÈÁÔÓÔ-·ÚÔ˘ÛÈ·ÛÙÈο ·ÙÙ·Ú· (APC) ·ÔÙÂÏÔ‡Ó À¿Ú¯Ô˘Ó ›Û˘ Fc ˘Ô‰Ô¯Â›˜ (FcRs), ˘Ô‰Ô¯Â›˜ ÙÔ ÎÏÂȉ› Ù˘ Û‡Ó‰ÂÛ˘ ÌÂٷ͇ Ù˘ Ê˘ÛÈ΋˜ Î·È ÂȉÈ- Ì·Ófi˙˘ (ªƒs) Î·È ˘Ô‰Ô¯Â›˜ ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ ΋˜ ·ÓÔÛ›·˜. ¢È·ÎÚ›ÓÔ˘Ì ÙÚÂȘ Ù‡Ô˘˜ ·ÓÙÈÁÔÓÔ-·- C3b3. ÕÏÏÔ˜ ÙÚfiÔ˜ ·Ó·ÁÓÒÚÈÛ˘ Â›Ó·È Ë Ô„ˆÓÔÔ›- ÚÔ˘ÛÈ·ÛÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ: Ù· Ì·ÎÚÔÊ¿Á·, Ù· ‰ÂÓ‰ÚÈÙÈ- ËÛË Ì ÎÏ¿ÛÌ·Ù· ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ Î·È ·ÓÙÈÛÒÌ·- ο Î·È Ù· μ-ÏÂÌÊÔ·ÙÙ·Ú·. Ù·. ΔÔ C3 ÎÏ¿ÛÌ· ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ Â›Ó·È ¿ÊıÔ- ™ËÌ·ÓÙÈÎfi ·ÓÙÈÁÔÓÔ-·ÚÔ˘ÛÈ·ÛÙÈÎfi Â›Ó·È ÙÔ ‰ÂÓ- ÓÔ ÛÙÔ Ï¿ÛÌ·, ÂÈοıÂÙ·È ÛÙËÓ ÂÈÊ¿ÓÂÈ· ÙˆÓ ÌÈ- ‰ÚÈÙÈÎfi ·ÙÙ·ÚÔ, Ô˘ ηٿ ÔÏÏÔ‡˜ ıˆÚÂ›Ù·È fiÙÈ ÎÚÔ‚›ˆÓ Û ·ÓÙ›ÛÙÔÈ¯Ô˘˜ ˘Ô‰Ô¯Â›˜ Ô˘ ˘¿Ú¯Ô˘Ó ·ÔÙÂÏ› ÙËÓ ÂÍÂÏÈÎÙÈ΋ ÌÔÚÊ‹ ÙˆÓ ÌÔÓÔ‡ÚËÓˆÓ Î·È Î·Ù¿ ·˘ÙfiÓ ÙÔÓ ÙÚfiÔ ·Ó·ÁÓˆÚ›˙ÔÓÙ·È ·fi Ù· Ê·ÁÔ΢ÙÙ¿ÚˆÓ. ªÂϤÙ˜ ·Ô‰ÂÈÎÓ‡Ô˘Ó fiÙÈ ¤¯Ô˘Ó Ê·ÁÔ·ÙÙ·Ú·. ∏ ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ ÏÂÌÊÔÂȉ‹ Î·È Ì˘ÂÏÔÁÂÓ‹ ηٷÁˆÁ‹. Œ¯Ô˘Ó ¯·Ú·ÎÙË- Á›ÓÂÙ·È Ì ÙËÓ ÂÓ·ÏÏ·ÎÙÈ΋ Ô‰fi, Ë ÔÔ›· ¤¯ÂÈ ÙËÓ ›‰È· ÚÈÛÙÈ΋ ÌÔÚÊÔÏÔÁ›· ‰È·ÎÏ·‰ÒÛÂˆÓ Î·È ‚Ú›ÛÎÔÓÙ·È ÌÈÎÚÔ‚ÈÔÎÙfiÓÔ ‰Ú¿ÛË Ì ÙËÓ ÎÏ·ÛÈ΋ Ô‰fi Ì ÙÔ ÏÂ- ·ÔÎÏÂÈÛÙÈο ÛÙËÓ Δ Î˘ÙÙ·ÚÈ΋ ÂÚÈÔ¯‹ ÙÔ˘ ÏÂÌÊÈÎÔ‡ ÔÓ¤ÎÙËÌ· fiÙÈ ÂÓÂÚÁÔÔÈÂ›Ù·È Ù·¯‡Ù·Ù·. ∏ ÎÏ·ÛÈ΋ ÈÛÙÔ‡. ∏ ÂÓÂÚÁÔÔ›ËÛË Ù˘ ÂȉÈ΋˜ ·ÓÔÛ›·˜ ‰ÂÓ Ï·Ì- Ô‰fi˜ ÁÈ· Ó· ÂÓÂÚÁÔÔÈËı› ¯ÚÂÈ¿˙ÂÙ·È 5-7 ̤Ú˜, ‚¿ÓÂÈ Ì¤ÚÔ˜ ÛÙËÓ ÂÚÈÔ¯‹ Ù˘ ÊÏÂÁÌÔÓ‹˜, ·ÏÏ¿ ÛÙ· Ã. ÕÓÙ˙ÈÔ˘-∞ÁÁÔ˘Úȉ¿ÎË 21
ÂÚÈÊÂÚÈο ÏÂÌÊÈο fiÚÁ·Ó·. ∂Λ ÌÂٷʤÚÂÙ·È ÙÔ APC Ú›ˆ˜ ·fi ÙË Ê‡ÛË Ù˘ ·ÓÔÛȷ΋˜ ·¿ÓÙËÛ˘. Δ· Δ- ·ÙÙ·ÚÔ, ¤¯ÔÓÙ·˜ ÙÔ ·ÓÙÈÁfiÓÔ ÙÔ ÔÔ›Ô ·ÚÔ˘ÛÈ¿˙ÂÙ·È ÏÂÌÊÔ·ÙÙ·Ú· ˆ˜ ·¿ÓÙËÛË ÛÙËÓ ·ÓÔÛÔÏÔÁÈ΋ ‰È¤- ÛÙ· ·ıÒ· (naive) ÏÂÌÊÔ·ÙÙ·Ú·. ªÂ ÙËÓ ·Ó·ÁÓÒÚÈÛ‹ ÁÂÚÛË ÂÎÎÚ›ÓÔ˘Ó Î˘ÙÙ·ÚÔΛÓ˜, Ô˘ ÚÔ¿ÁÔ˘Ó ÙÔÓ ÙÔ˘ ÍÂÎÈÓ¿ Ë ÂÓÂÚÁÔÔ›ËÛË Î·È Ô ÔÏÏ·Ï·ÛÈ·ÛÌfi˜ ÔÏÏ·Ï·ÛÈ·ÛÌfi Î·È Ù ‰È·ÊÔÚÔÔ›ËÛË ÙˆÓ μ-΢ÙÙ¿- ÙÔ˘ ΢ÙÙ¿ÚÔ˘ Î·È ·’ ÙÔ ·Ú¯ÈÎfi ÏÂÌÊÔ·ÙÙ·ÚÔ ·Ú¿- ÚˆÓ, fiˆ˜ IL2, IL5, IL4. ∏ IL6 Ô˘ ·Ú¿ÁÂÙ·È ·fi Ù· ÁÂÙ·È ÛÙÚ·ÙÈ¿ Δ-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ ÁÈ· ÙÔ Û˘ÁÎÂÎÚÈ̤ÓÔ Ì·ÎÚÔÊ¿Á·, Ù· Δ Î·È ¿ÏÏ· ·ÙÙ·Ú· ·ÔÙÂÏ› ·˘ÍËÙÈ- ·ÓÙÈÁfiÓÔ. Δ· ÂÓÂÚÁÔÔÈË̤ӷ Δ-ÏÂÌÊÔ·ÙÙ·Ú·, Ô˘ Îfi ·Ú¿ÁÔÓÙ· ÙˆÓ ‹‰Ë ‰È·ÊÔÚÔÔÈËÌ¤ÓˆÓ Ï·ÛÌ·- ÌÂÙ·ÙÚ¤ÔÓÙ·È Û ‰Ú·ÛÙÈο ΢ÙÙ·ÚÔÙÔÍÈο (CTLs), ÌÂ- ÙÔ΢ÙÙ¿ÚˆÓ. ∏ INFÁ ÙˆÓ CD4 ÂÓÂÚÁÔÔÈ› Ù· Ì·- ٷʤÚÔÓÙ·È ›Ûˆ ÛÙÔ ÛËÌÂ›Ô Ù˘ Ïԛ̈͢ fiÔ˘ ı· ÎÚÔÊ¿Á· Î·È Ô Δ¡F ÚÔÛÂÏ·ÂÈ ¿ÏÏ· Ê·ÁÔ·ÙÙ·Ú· ηٷÛÙÚ¤„Ô˘Ó ÌÔÏ˘Ṳ̂ӷ ·ÙÙ·Ú·. ÛÙËÓ ÂÚÈÔ¯‹ Ù˘ Ïԛ̈͢. Δ· Ì·ÎÚÔÊ¿Á· ÂÎÎÚ›- ∏ ·ÚÔ˘Û›·ÛË ÙÔ˘ ·ÓÙÈÁfiÓÔ˘ Á›ÓÂÙ·È Ì¤Ûˆ ÙÔ˘ ÓÔ˘Ó IL12, IL18, IL23 Î·È ÂÓÂÚÁÔÔÈÔ‡Ó ÙËÓ Δ-helper Ì›˙ÔÓÔ˜ Û˘ÌϤÁÌ·ÙÔ˜ ÈÛÙÔÛ˘Ì‚·ÙfiÙËÙÔ˜ MHC 1 (Δh1) Ù‡Ô˘ ·¿ÓÙËÛË (ÂÓ‰Ô΢ÙÙ¿ÚÈ· ‚·ÎÙ‹ÚÈ·)6. (major histocompatibility complex). Δ· ÌfiÚÈ· ·˘Ù¿ ΔÔ ·ÓÔÛÈ·Îfi Ì·˜ Û‡ÛÙËÌ· Â›Ó·È ¤Ó· Û‡ÛÙËÌ· ·ÔÙÂÏÔ‡Ó ÌÂÌ‚Ú·ÓÈΤ˜ ÁÏ˘ÎÔÚˆÙ½Ó˜. ¢‡Ô Ù¿ÍÂȘ ·Ú›ÛÙ˘ Û˘ÓÂÚÁ·Û›·˜ ÔÈÎ›ÏˆÓ Î˘ÙÙ¿ÚˆÓ, Ô ‰Â ‰È·- ÌÔÚ›ˆÓ ‰È·ÎÚ›ÓÔ˘ÌÂ, ÙÔ MHC Ù¿Í˘ π Î·È ÙÔ MHC ¯ˆÚÈÛÌfi˜ ÛÂ Ê˘ÛÈ΋ Î·È Â›ÎÙËÙË ·ÓÔÛ›· Â›Ó·È Î·ı·- Ù¿Í˘ II. Δ· ΢ÙÙ·ÚÔÙÔÍÈο Δ-ÏÂÌÊÔ·ÙÙ·Ú· CD8+ Ú¿ ÂÚÈÁÚ·ÊÈÎfi˜. √È Ì˯·ÓÈÛÌÔ› Ù˘ Ê˘ÛÈ΋˜ ·ÓÔ- ·Ó·ÁÓˆÚ›˙Ô˘Ó ·ÓÙÈÁfiÓÔ Ô˘ ·ÚÔ˘ÛÈ¿˙ÂÙ·È Ì ٷ Ìfi- Û›·˜ ÛÙÔ¯Â‡Ô˘Ó ÛÙËÓ ¿ÌÂÛË ·ÓÙÈÌÂÙÒÈÛË ÔÔÈÔ˘‰‹- ÚÈ· MHC Ù¿Í˘ π, ÂÓÒ Ô ˘ÔÏËı˘ÛÌfi˜ Δ-‚ÔËıËÙÈο ÔÙ ·ıÔÁfiÓÔ˘ Ì ʷÁÔ΢ÙÙ¿ÚˆÛË, ÂÓÂÚÁÔÔ›ËÛË CD4 ·Ó·ÁÓˆÚ›˙ÂÈ ·ÓÙÈÁfiÓ· Ì ٷ ÌfiÚÈ· MHC Ù¿Í˘ ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜, ·Ú·ÁˆÁ‹ ΢ÙÙ·ÚÔÎÈÓÒÓ Ì ÙÂ- ππ Î·È Ë ·Ó·ÁÓÒÚÈÛË Á›ÓÂÙ·È Ì ÙÔ˘˜ ˘Ô‰Ô¯Â›˜ ÙˆÓ Δ- ÏÈÎfi ÚÔÔÚÈÛÌfi ÙË ‰È¤ÁÂÚÛË Ù˘ ›ÎÙËÙ˘ ·ÓÔÛ›·˜. ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ (TCR) Î·È Ì ÙËÓ ··Ú·›ÙËÙË ‚Ô‹- ∏ ·ÓÔÛȷ΋ ·¿ÓÙËÛË Â›Ó·È ÌÈ· Û˘Ó¯‹˜ ÔÏ˘Â›Â- ıÂÈ· ÙˆÓ Û˘Ó‰ÈÂÁÂÚÙÒÓ fiˆ˜: CD28 ÙˆÓ Δ-΢ÙÙ¿ÚˆÓ ‰Ë Î·È ÔÏ˘‰‡Ó·ÌË ‰È·‰Èηۛ·, ¯·Ú·ÎÙËÚÈ˙fiÌÂÓË ·- Ì ÙÔ μ7 ÙˆÓ Ì·ÎÚÔÊ¿ÁˆÓ (CD28/B7). Δ· Δ-ÏÂÌÊÔ- fi ÌÂÁ¿ÏÔ ÚÂÂÚÙfiÚÈÔ ˘Ô‰Ô¯¤ˆÓ ÈηÓfi ÁÈ· ·Ó·- ·ÙÙ·Ú· ¤¯Ô˘Ó ÙËÓ ÈηÓfiÙËÙ· ·Ó›¯Ó¢Û˘ Î·È ·Ó·- ÁÓÒÚÈÛË ·Â›ÚˆÓ Í¤ÓˆÓ ·ÓÙÈÁfiÓˆÓ, ̤ۈ ÙˆÓ ÔÔ›ˆÓ ÁÓÒÚÈÛ˘ ·ÓÙÈÁfiÓˆÓ, Ù· ÔÔ›· ‰ËÌÈÔ˘ÚÁÔ‡ÓÙ·È ÛÙÔ ÂÈÙÂÏÂ›Ù·È ÙÔ ı·‡Ì· Ù˘ ˙ˆ‹˜. ÂÛˆÙÂÚÈÎfi ÙˆÓ ÚÔÛ‚ÏËı¤ÓÙˆÓ Î˘ÙÙ¿ÚˆÓ (.¯., ÈÔÁÂ- Ó›˜ ÏÔÈÌÒÍÂȘ)5. μÈ‚ÏÈÔÁÚ·Ê›· √ ΢ڛ·Ú¯Ô˜ ÏËı˘ÛÌfi˜ ÂÍÔ˘‰ÂÙ¤ÚˆÛ˘ ÙˆÓ ÂÍˆÎ˘ÙÙ¿ÚÈˆÓ ·ıÔÁfiÓˆÓ Gram+ Gram – ÎfiÎÎˆÓ 1. Janway Ch.A, Travers P. ∫ÏÈÓÈ΋ ∞ÓÔÛÔÏÔÁ›·. ΔÔ ·ÓÔÛÔÏÔ- ÁÈÎfi Û‡ÛÙËÌ· ÛÙËÓ ˘Á›· Î·È ÙË ÓfiÛÔ. 2Ë ∂Ή. ¶·Û¯·Ï›- Â›Ó·È Ù· CD4+. ‰Ë˜, 2002, ÎÂÊ. 9:1-9:46. Δ· μ-·ÙÙ·Ú· ¤¯Ô˘Ó ˘Ô‰Ô¯Â›˜ ·Ó·ÁÓÒÚÈÛ˘ 2. Leung AYH, Verfaillie CM. Stem cell model of hematopoi- ÌÂÌ‚Ú·ÓÈΤ˜ ·ÓÔÛÔÛÊ·ÈÚ›Ó˜. Δ· ·ÓÙÈÛÒÌ·Ù· Ô˘ isis. In: Hoffman R, Benz E, Shatill SJ, Furie B, Cohen HJ, ΢ÎÏÔÊÔÚÔ‡Ó Â›Ó·È Ô ÂÎÎÚÈÓfiÌÂÓÔ˜ Ù‡Ô˜ ÙÔ˘ ·ÓÙÈ- Silberstein LE, McGave P. Haematology, basic principles ÁÔÓÔÂȉÈÎÔ‡ ˘Ô‰Ô¯¤· ÙˆÓ μ-΢ÙÙ¿ÚˆÓ Î·È ·Ú¿ÁÔ- and practice. 4th Edition, Elservier Churchill Livingstone, ÓÙ·È Û ÌÂÁ¿Ï˜ ÔÛfiÙËÙ˜ Û ·¿ÓÙËÛË ÛÙÔ ·ÓÙÈÁfi- 2005: 3295-3313. ÓÔ. Δ· μ-·ÙÙ·Ú· ·Ó·ÁÓˆÚ›˙Ô˘Ó ·ÓÙÈÁfiÓ· ¤Ú· Î·È 3. Abbas AK. Lichtman AH, Pober JS. Cellular and molecular immunology. 4th ed. Saunders, 1994, 173: 131-140. ¤Íˆ ·fi ÙÔ Î‡ÙÙ·ÚÔ ÙÔ˘ ÔÚÁ·ÓÈÛÌÔ‡ (.¯., ‚·ÎÙËÚÈ·- 4. The inflammatory response. In: Leonard H S, Yacov R. Im- Τ˜ ÏÔÈÌÒÍÂȘ). Œ¯Ô˘Ó ›Û˘ ÙËÓ ÈηÓfiÙËÙ· ·ÚÔ˘- munology and inflammation Basic Mechanisms and cli- Û›·Û˘ ÙÔ˘ ·ÓÙÈÁfiÓÔ˘ Ì ÙÔ MHC Ù¿Í˘ ππ ÛÙ· ÂȉÈο nical consequences. McGraw-Hill inc, USA, 1994, Cha- ‚ÔËıËÙÈο ·ÙÙ·Ú·, CD4. pter 20: 361-386. ¶·Ú·ÙËÚԇ̠ÏÔÈfiÓ ÙËÓ ÂÎÏËÎÙÈ΋ Û˘ÓÂÚÁ·- 5. David S, et al. Immune response to extra cellular bacteria. Û›· Î·È ·ÏÏËÏÂÍ¿ÚÙËÛË ÌÂٷ͇ ÙˆÓ ‰È·ÊfiÚˆÓ Ù‡ˆÓ In: Robert R, Rich et al. Clinical immunology principles and practice. 3rd Edition, Mosby-Elsevier, 2008, 377. ΢ÙÙ¿ÚˆÓ. ∫ÂÓÙÚÈÎfi Î·È Ú˘ıÌÈÛÙÈÎfi ÚfiÏÔ ¤¯Ô˘Ó ÔÈ 6. Steffen HE, Kaufmann et al. Immune response to intracel- ΢ÙÙ·ÚÔΛÓ˜, ÔÈ Ôԛ˜ ÂÌÊ·Ó›˙Ô˘Ó ‰È·ÊÔÚÂÙÈΤ˜ lular bacteria. In: Robert R, Rich et al. Clinical immuno- ÏÂÈÙÔ˘ÚÁ›Â˜ ÂÍ·ÚÙÒÌÂÓ˜ ·fi ÙËÓ Î˘ÙÙ·ÚÈ΋ ËÁ‹ logy principles and practice. 3rd Edition, Mosby-Elsevier, ÚÔ¤ÏÂ˘Û‹˜ ÙÔ˘˜, ·fi Ù· ·ÙÙ·Ú·-ÛÙfi¯Ô˘˜ Î·È Î˘- 2008, 389. AÓÔÛÔÏÔÁ›· Ïԛ̈͢
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2009; 1: 22 – 26
∏ ·ÓÔÛȷ΋ ·fiÎÚÈÛË ÛÙË Ïԛ̈ÍË ÂÍ·ÚÙ¿Ù·È ·fi Ùfi, ÙË ‰È·ÛÔÚ¿ Ù˘ Ïԛ̈͢, ‚) Ó· ·Ó·ÁÓˆÚ›ÛÂÈ Ì¤- ÙËÓ ·ÓÔÛȷ΋ ηٿÛÙ·ÛË ÙÔ˘ ÍÂÓÈÛÙ‹ Î·È ·fi ·Ú¿- Ûˆ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ù˘ Ê˘ÛÈ΋˜ ·ÓÔÛ›·˜ (Pattern ÁÔÓÙ˜ Ô˘ ¤¯Ô˘Ó Û¯¤ÛË Ì ÙÔ ·ıÔÁfiÓÔ, fiˆ˜ Ë Recognition Receptors, PRRs) ÌÔÚȷΤ˜ ‰Ô̤˜ ÙˆÓ Ù·ÍÈÓfiÌËÛ‹ ÙÔ˘ (‚·ÎÙ‹ÚÈÔ, Èfi˜ ·Ú¿ÛÈÙÔ, ̇ÎËÙ·˜), Ë ·ıÔÁfiÓˆÓ (Pathogen Associated Molecular Pat- ÌÔÚÊ‹ (‚Ï·ÛÙÈ΋, ΢ÛÙÈ΋), Ë ÏÔÈÌÔÁfiÓÔ˜ ‰‡Ó·ÌË, Ë terns, PAMPs), ÁÓˆÛÙÔÔÈÒÓÙ·˜ ÛÙÔ ·ÓÔÛÈ·Îfi Û‡- ‡ÏË ÂÈÛfi‰Ô˘ ÛÙÔÓ ÔÚÁ·ÓÈÛÌfi (‚ÏÂÓÓÔÁfiÓÔÈ, ·ÚÂ- ÛÙËÌ· ÙË Ê‡ÛË ÙÔ˘˜, Î·È Á) Ó· ¿ÁÂÈ ÙËÓ ¤Ó·ÚÍË Ù˘ ÓÙÂÚÈ΋ Ô‰fi˜), Ë ÊÏÂÁÌÔÓ҉˘ ·ÓÙ›‰Ú·ÛË Ô˘ ÚÔ- ÂȉÈ΋˜ ΢ÙÙ·ÚÈ΋˜ ·ÓÔÛ›·˜1-4. ηÏ› (ÙÔÈ΋, ÁÂÓÈÎÂ˘Ì¤ÓË) Î·È Ë ı¤ÛË ÔÏÏ·Ï·ÛÈ·- √È Ì˯·ÓÈÛÌÔ› Ù˘ ΢ÙÙ·ÚÈ΋˜ ·ÓÔÛ›·˜ Â›Ó·È Î·- ÛÌÔ‡ ÙÔ˘ (ÂÍˆÎ˘ÙÙ¿ÚÈ·, ÂÓ‰Ô΢ÙÙ¿ÚÈ·)1. ıÔÚÈÛÙÈ΋˜ ÛËÌ·Û›·˜ ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÏÔÈÌÒ- Δ· ÂÓ‰Ô΢ÙÙ¿ÚÈ· ‚·ÎÙ‹ÚÈ· ¤¯Ô˘Ó ÙËÓ ÈηÓfiÙË- ÍÂˆÓ ·fi ÂÓ‰Ô΢ÙÙ¿ÚÈ· ·ıÔÁfiÓ· Î·È ˘fi ÚÔ¸Ô- Ù· Ó· ÂÈ‚ÈÒÓÔ˘Ó Î·È Ó· ÔÏÏ·Ï·ÛÈ¿˙ÔÓÙ·È ÛÙ· Ì·- ı¤ÛÂȘ Ô‰ËÁÔ‡Ó ÙÂÏÈο ÛÙËÓ ÂÎÚ›˙ˆÛË Ù˘ Ïԛ̈͢1- ÎÚÔÊ¿Á· ÙÔ˘ ÍÂÓÈÛÙ‹ ÚÔηÏÒÓÙ·˜ Û˘¯Ó¿ ¯ÚfiÓÈ· 3. ∏ ΢ÙÙ·ÚÈ΋ ·ÓÔÛ›· ¤Ó·ÓÙÈ ÙˆÓ ÂÓ‰Ô΢ÙÙ¿ÚÈˆÓ ·- ÓfiÛÔ. √ÚÈṲ̂ӷ ÂÓ‰Ô΢ÙÙ¿ÚÈ· ‚·ÎÙ‹ÚÈ· (Mycoba- ıÔÁfiÓˆÓ Î·È Â›Ó·È Th1 Ù‡Ô˘ (·Ú·ÁˆÁ‹ IL-2 Î·È cterium, Brucella, Legionella, Chlamydia) ·Ú·ÛÈÙÔ‡Ó IFNÁ). ∏ ·ÂÏ¢ı¤ÚˆÛË IFNÁ ·fi Ù· CD4+ Î·È Ù· Û ΢ÛÙÈÎÔ‡˜ Û¯ËÌ·ÙÈÛÌÔ‡˜ ÙÔ˘ ΢ÙÙ·ÚÔÏ¿ÛÌ·ÙÔ˜ CD8+ (΢ÙÙ·ÚÔÙÔÍÈο) Δ-ÏÂÌÊÔ·ÙÙ·Ú·: ·) ÂËÚ¿- Ô˘ ‰È·ÌÔÚÊÒÓÔÓÙ·È ·fi ·Ó·‰ÈÏÒÛÂȘ Ù˘ ΢ÙÙ·ÚÈ- ˙ÂÈ ‹ ·Ó·ÛÙ¤ÏÏÂÈ Ï‹Úˆ˜ ÙËÓ ÈηÓfiÙËÙ· ÙÔ˘ ·ıÔÁfi- ΋˜ ÌÂÌ‚Ú¿Ó˘ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ Ê·ÁÔ΢ÙÙ¿Úˆ- ÓÔ˘ Ó· ÂÈ‚ÈÒÓÂÈ Ì¤Û· ÛÙ· Ì·ÎÚÔÊ¿Á·, ‚) ·Ú¤¯ÂÈ Û˘ Î·È Ô-ÓÔÌ¿˙ÔÓÙ·È Ê·ÁÔۈ̿ÙÈ·. ÕÏÏ· (Listeria, ÙËÓ Î·Ù¿ÏÏËÏË ‚Ô‹ıÂÈ· ÁÈ· ÙË ‰È¤ÁÂÚÛË ÙˆÓ CD8+ T- Shigella, Rickettsia) Ï·ıÚÔ‚ÈÒÓÔ˘Ó ÂχıÂÚ· ÛÙÔ Î˘Ù- ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ Ô˘ ÊÔÓÂ‡Ô˘Ó Ù· ÌÔÏ˘Ṳ̂ӷ ·ÙÙ·- Ù·ÚfiÏ·ÛÌ·1-3. Ú· Î·È Á) ÂÓÈÛ¯‡ÂÈ ÙËÓ ·Ú·ÁˆÁ‹ ·ÓÙÈÛˆÌ¿ÙˆÓ ·fi ™Â οı ÂÚ›ÙˆÛË ÙÔ ·ÓÔÛÈ·Îfi Û‡ÛÙËÌ· ÙÔ˘ Ù· μ-ÏÂÌÊÔ·ÙÙ·Ú·, Ù· ÔÔ›· ÂÓÂÚÁÔÔÈÔ‡Ó ÙÔ Û˘- ·ÓıÚÒÔ˘ ¤¯ÂÈ ·Ó·Ù‡ÍÂÈ Ì˯·ÓÈÛÌÔ‡˜ ¿Ì˘Ó·˜, ÌË Ìϋڈ̷ Î·È Â¿ÁÔ˘Ó Ô„ˆÓÈÓÔÔ›ËÛË1,3,5. ÂȉÈÎÔ‡˜ (Ê˘ÛÈ΋ ·ÓÔÛ›·) Î·È ÂȉÈÎÔ‡˜ (›ÎÙËÙË ·ÓÔ- ŒÓ·ÓÙÈ ÙˆÓ ·Ú·¿Óˆ Ì˯·ÓÈÛÌÒÓ Ù· ÂÓ‰Ô΢Ù- Û›·), ÚÔÎÂÈ̤ÓÔ˘ Ó· ·ÓÙÈÌÂÙˆ›ÛÂÈ Ù· ·Ú·¿Óˆ ·- Ù¿ÚÈ· ·ıÔÁfiÓ· ¤¯Ô˘Ó ·Ó·Ù‡ÍÂÈ Ì˯·ÓÈÛÌÔ‡˜ ‰È·- ıÔÁfiÓ·1-3. ∏ ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ Î˘ÙÙ¿ÚˆÓ Ù˘ Ê˘ÛÈ- Ê˘Á‹˜ ·fi ÙÔ ·ÓÔÛÈ·Îfi Û‡ÛÙËÌ· ÙÔ˘ ÍÂÓÈÛÙ‹, ÚÔ- ΋˜ ·ÓÔÛ›·˜ (Ì·ÎÚÔÊ¿Á·, ‰ÂÓ‰ÚÈÙÈο, Ô˘‰ÂÙÂÚfiÊÈÏ·, ÎÂÈ̤ÓÔ˘ Ó· ¢ԉÒÛÔ˘Ó ÙÔÓ ·Ú·ÛÈÙÈÛÌfi ÙÔ˘˜ Î·È Ó· ¡∫ ·ÙÙ·Ú·, Á‰-Δ ÏÂÌÊÔ·ÙÙ·Ú·) Ú·ÁÌ·ÙÔÔÈÂ›Ù·È ÂÈ‚ÈÒÛÔ˘Ó5-6. ÛÙ· ÚÒÙ· ÛÙ¿‰È· ÂÈÛ‚ÔÏ‹˜ ÙÔ˘ ÂÓ‰Ô΢ÙÙ¿ÚÈÔ˘ ·- ∏ ‚ÚԢΤÏψÛË Â›Ó·È Ì›· ÎÏ·ÛÈ΋ ÂÓ‰Ô΢ÙÙ¿ÚÈ·, ıÔÁfiÓÔ˘ Î·È Î·Ù¿ ÌË ÂȉÈÎfi ÙÚfiÔ Ô˘ ÛÙÂÚÂ›Ù·È ÎÔÎÎȈ̷Ù҉˘, ‚·ÎÙËÚȷ΋ Ïԛ̈ÍË Î·È ·ÓÙÈÚÔÛˆ- ·ÓÔÛȷ΋˜ ÌÓ‹Ì˘. Œ¯ÂÈ ˆ˜ ÛÎÔfi: ·) Ó· ·ÓÙÈÌÂÙˆ›- ‡ÂÈ ÙË Û˘¯ÓfiÙÂÚË ˙ˆÔ·ÓıÚˆÔÓfiÛÔ Ì ¢Ú›· ‰È·- ÛÂÈ ¿ÌÂÛ· Ù· ‚·ÎÙ‹ÚÈ· ÂÚÈÔÚ›˙ÔÓÙ·˜, ηٿ ÙÔ ‰˘Ó·- ÛÔÚ¿ ·ÁÎÔÛÌ›ˆ˜, ΢ڛˆ˜ ÛÙÔÓ ·Ó·Ù˘ÛÛfiÌÂÓÔ Îfi- ¶. ™Î¤Ó‰ÚÔ˜ 23
ÛÌÔ7. À‡ı˘Ó· ÁÈ· ÙË ÓfiÛÔ Â›Ó·È ÂÓ‰Ô΢ÙÙ¿ÚÈ·, gram ÏˆÓ ·ÓÙÈÌÈÎÚÔ‚È·ÎÒÓ ÂÙȉ›ˆÓ fiˆ˜ Ë ÓÙÂÊÂÓÛ›ÓË, Ë ·ÚÓËÙÈο ‚·ÎÙ‹ÚÈ· ÙÔ˘ Á¤ÓÔ˘˜ μÚԢΤÏÏ· (Brucella)8. Ï·ÎÙÔÊÂÚÚ›ÓË Î·È Ë Ï˘ÛÔ˙‡ÌË11,16-18. ∂ÈϤÔÓ, Ô LPS ¶·Ú¿ ÙÔÓ ¤ÏÂÁ¯Ô ‹ ÙËÓ ÂÍ¿ÏÂÈ„Ë Ù˘ ‚ÚԢΤÏψÛ˘ ¿ÁÂÈ ÙËÓ in vitro ·Ú·ÁˆÁ‹ IL-10 ·fi Ù· ·ÓıÚÒÈ- ·fi ÔÚÈṲ̂Ó˜ ¯ÒÚ˜, Ë ÓfiÛÔ˜ Û˘Ó¯›˙ÂÈ Ó· ÚÔηÏ› Ó· ÌÔÓÔ‡ÚËÓ·, Ë ÔÔ›· ηٷÛÙ¤ÏÏÂÈ ÙËÓ Th1 ·fi- ÛÔ‚·Ú¤˜ ÂÈÙÒÛÂȘ ÛÙËÓ ÔÈÎÔÓÔÌ›· Î·È ÙË ‰ËÌfiÛÈ· ÎÚÈÛË19. ∏ in vitro ‰È¤ÁÂÚÛË ÙˆÓ ·ÓıÚÒÈÓˆÓ Ì·ÎÚÔ- ˘Á›· ÙˆÓ ¯ˆÚÒÓ ÛÙȘ Ôԛ˜ ÂÓ‰ËÌ›, Û˘ÌÂÚÈÏ·Ì‚·ÓÔ- Ê¿ÁˆÓ Ì ‚ÚԢΤÏÏ· ·˘Í¿ÓÂÈ ÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ ̤Ó˘ Î·È Ù˘ ‰È΋˜ Ì·˜7. ªÂÙ·‰›‰ÂÙ·È ·fi Ù· ·ÈÁÔÚfi- CD80 ÌÔÚ›Ô˘ Ô˘ Ô‰ËÁ› ÛÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ ‚·Ù·, Ù· ‚ÔÔÂȉ‹, ÙÔ˘˜ ¯Ô›ÚÔ˘˜, Û·ÓÈfiٷٷ ·fi ÙÔ˘˜ Th1 ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ Ì¤Ûˆ Ù˘ CD80/CD28 Û˘Ó- Û·ÏÔ˘˜, ÂÓÒ ¤¯Ô˘Ó ·Ó·ÊÂÚı› Î·È ÌÂÌÔӈ̤Ó˜ ÂÚÈ- ‰ÈÂÁÂÚÙÈ΋˜ Ô‰Ô‡. øÛÙfiÛÔ, Ë ·‡ÍËÛË ÙˆÓ CD14+/ ÙÒÛÂȘ ÌÂÙ¿‰ÔÛ˘ ·fi ıËÏ·ÛÙÈο Ù˘ ı¿Ï·ÛÛ·˜7,8. CD80+ ΢ÙÙ¿ÚˆÓ Û ·ÛıÂÓ›˜ Ì ‚ÚԢΤÏψÛË ÌÂ- ∞ÓÂÍ¿ÚÙËÙ· ·fi ÙË ıÂڷ›· ÌÂÙ·›ÙÂÈ ÔÏϤ˜ ÊÔÚ¤˜ Ù¿ ·fi in vitro ‰È¤ÁÂÚÛË Ì ‚ÚԢΤÏÏ· Â›Ó·È ÌÈÎÚfi- Û ¯ÚÔÓÈfiÙËÙ·, Ë ÔÔ›· ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ¿Ù˘Ë ÎÏÈ- ÙÂÚË ·fi ·˘Ù‹ Ô˘ ÚÔηÏ› Ô LPS Ù˘ E. Coli20-22. ÓÈ΋ Û˘ÌÂÚÈÊÔÚ¿ Î·È ˘ÔÙÚÔ¤˜9,10-12. ∂ÈϤÔÓ Ù· ›- ÕÏÏÔÈ PAMPs Ô˘ Û˘Ì‚¿ÏÏÔ˘Ó ÛÙËÓ ÂÈ‚›ˆÛË ‰Ë Ù˘ ‚ÚԢΤÏÏ·˜ ıˆÚÔ‡ÓÙ·È ‰˘ÓËÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ ÙˆÓ ‚ÚÔ˘ÎÂÏÏÒÓ Â›Ó·È Ë ÔÚ›ÓË Omp25 Ô˘ ηٷ- ‚ÈÔÙÚÔÌÔÎÚ·Ù›·˜ ‰Â‰Ô̤ÓÔ˘ fiÙÈ ÌÔÚÔ‡Ó Â‡ÎÔÏ· Ó· ÛÙ¤ÏÏÂÈ ÙË Û‡ÓıÂÛË TNF· ·fi Ù· ·ÓıÚÒÈÓ· Ì·ÎÚÔ- ‰È·Û·ÚıÔ‡Ó Î·È Ó· ÚÔÛ‚¿ÏÔ˘Ó ÌÂÁ¿ÏÔ ·ÚÈıÌfi ÏË- Ê¿Á· Î·È Ë ÏÈÔÚˆÙ½ÓË Omp19 Ô˘ ·Ó·ÛÙ¤ÏÏÂÈ ÙËÓ ı˘ÛÌÔ‡ ̤ۈ ÙÔ˘ ·Ó·Ó¢ÛÙÈÎÔ‡. ™˘ÓÂÒ˜ ··ÈÙÂ›Ù·È ˘- ¤ÎÊÚ·ÛË MHC-II ÌÔÚ›ˆÓ Î·È ÙËÓ ÂÂÍÂÚÁ·Û›· ÙÔ˘ „ËÏ‹ ‰È·ÁÓˆÛÙÈ΋ ÈηÓfiÙËÙ· Î·È ·˘ÍË̤ÓË ÂȉËÌÈÔ- ·ÓÙÈÁfiÓÔ˘ ÛÙ· ›‰È· ·ÙÙ·Ú·23,24. ¶ÚfiÛÊ·Ù· ¤¯ÂÈ Î·- ÏÔÁÈ΋ ÂÈÙ‹ÚËÛË Û ÂÓ‰ËÌÈΤ˜ ‹ ÌË ÂÚÈÔ¯¤˜8,13. Ù·‰Âȯı› fiÙÈ ÔÈ ‚ÚԢΤÏϘ ÌÏÔοÚÔ˘Ó ÙË ‰È·Ì¤- Δ· Ì·ÎÚÔÊ¿Á· ·Ú·ı¤ÙÔ˘Ó ÈÛ¯˘Ú¿ ·ÓÙÈÌÈÎÚÔ- ÛÔ˘ ÙˆÓ Toll ˘Ô‰Ô¯¤ˆÓ (TLRs) ÛËÌ·ÙÔ‰fiÙËÛË ¯ÚË- ‚ȷο Û˘ÛÙ‹Ì·Ù· Î·È Ì˯·ÓÈÛÌÔ‡˜ ¤Ó·ÓÙÈ ÙˆÓ ‚ÚÔ˘- ÛÈÌÔÔÈÒÓÙ·˜ ÚˆÙ½Ó˜/ÔÌfiÏÔÁ· Ù˘ TIR ÂÚÈÔ¯‹˜ ÎÂÏÏÒÓ Ô˘ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó Ù· ˘‰ÚÔÏ˘ÙÈο ¤Ó˙˘Ì· ÙÔ˘ TLR (Toll/interleukin-1 receptor domain-contai- Î·È ÙÔ fiÍÈÓÔ pH ÙˆÓ Ê·ÁÔÏ˘ÛÔۈ̿وÓ, Ù· ·ÓÙÈÌÈ- ning proteins, Tcps)25,26. ÎÚԂȷο ÂÙ›‰È· (ÓÙÂÊÂÓÛ›Ó˜), ÙȘ ÂχıÂÚ˜ Ú›˙˜ ∂ÎÙfi˜ ÙˆÓ Ì·ÎÚÔÊ¿ÁˆÓ ÔÈ ‚ÚԢΤÏϘ ÌÔχ- Ô͢ÁfiÓÔ˘ Î·È ·˙ÒÙÔ˘ Î·È ÙËÓ ·Ú·ÁˆÁ‹ TNF·11,12, ÓÔ˘Ó ÈÛ¯˘Ú¿ Î·È Ù· ‰ÂÓ‰ÚÈÙÈο ·ÙÙ·Ú·, ÂÈ‚ÈÒÓÔ˘Ó 14,15. ∞fi ÙËÓ ¿ÏÏË ÌÂÚÈ¿, Ù· ÛÙÂϤ¯Ë ÙˆÓ ‚ÚÔ˘ÎÂÏ- Î·È ÔÏÏ·Ï·ÛÈ¿˙ÔÓÙ·È ÛÙÔ ÂÓ‰Ô΢ÙÙ¿ÚÈÔ ÂÚÈ‚¿Ï- ÏÒÓ ÚÔÎÂÈ̤ÓÔ˘ Ó· ÂÈ‚ÈÒÛÔ˘Ó Î·È Ó· ÔÏÏ·Ï·- ÏÔÓ ÙÔ˘˜27. ¡ÂfiÙÂÚ· ‰Â‰Ô̤ӷ ·Ó·Ê¤ÚÔ˘Ó fiÙÈ Ô ·- ÛÈ·ÛıÔ‡Ó ÛÙ· ·ÓıÚÒÈÓ· Ì·ÎÚÔÊ¿Á·, ¯ÚËÛÈÌÔÔÈ- Ú·¿Óˆ ·Ú·ÛÈÙÈÛÌfi˜ ·Ó·ÛÙ¤ÏÏÂÈ ÙËÓ ˆÚ›Ì·ÓÛË ÙˆÓ Ô‡Ó ÌÈ· ÛÂÈÚ¿ ·Ú·ÁfiÓÙˆÓ, fiˆ˜ ‰È¿ÊÔÚ˜ Úˆ- ‰ÂÓ‰ÚÈÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ Î·È ÙËÓ ·Ú·ÁˆÁ‹ IL-12 Î·È Ù½Ó˜ Î·È ÙÔÓ ÏÈÔÔÏ˘Û·Î¯·Ú›ÙË (LPS), ̤ۈ ÙˆÓ TNF· ·fi ·˘Ù¿. ΔÂÏÈο ÂËÚ¿˙ÂÙ·È ÛËÌ·ÓÙÈο Ë ·Ï- ÔÔ›ˆÓ ÙÚÔÔÔÈÔ‡Ó ÙË Ê·ÁÔ΢ÙÙ¿ÚˆÛË, ÙË Ê·ÁÔÏ˘- ÏËÏ›‰Ú·ÛË ÙˆÓ ‰ÂÓ‰ÚÈÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ Ì ٷ Δ-ÏÂÌ- ÛÔÛˆÌÈ΋ Û‡ÓÙËÍË, ÙËÓ ¤ÎÎÚÈÛË Î˘ÙÙ·ÚÔÎÈÓÒÓ Î·È ÙËÓ ÊÔ·ÙÙ·Ú· Î·È ‰ÂÓ Â¿ÁÂÙ·È ÈÛ¯˘Ú‹ Th1 ·fiÎÚÈÛË28. ·fiÙˆÛË11,12,16. ™‡Ìʈӷ Ì ٷ ·Ú·¿Óˆ, Ê·›ÓÂÙ·È fiÙÈ ÔÈ ‚ÚÔ˘- √ LPS ıˆÚÂ›Ù·È Î·ıÔÚÈÛÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ ÏÔÈ- ΤÏϘ ηٿ ÙËÓ ¤Ó·ÚÍË Ù˘ Ïԛ̈͢ ·Ó·Ù‡ÛÛÔ˘Ó ÌÔÁfiÓÔ˘ ‰‡Ó·Ì˘ Î·È ¯ÚfiÓÈÔ˘ ·Ú·ÛÈÙÈÛÌÔ‡ ÙˆÓ ÛÙÚ·ÙËÁÈΤ˜ Ô˘ Ô‰ËÁÔ‡Ó Û ÌÂÈÔÓÂÎÙÈ΋ ÂÓÂÚÁÔÔ›- ‚ÚÔ˘ÎÂÏÏÒÓ17. ¢È·Ê¤ÚÂÈ ‰ÔÌÈο Î·È ÏÂÈÙÔ˘ÚÁÈο ·fi ËÛË ÙˆÓ Î˘ÙÙ¿ÚˆÓ Ù˘ Ê˘ÛÈ΋˜ ·ÓÔÛ›·˜, ¤ÙÛÈ ÒÛÙ ÙÔÓ ÎÏ·ÛÈÎfi LPS ÙˆÓ ÂÓÙÂÚÔ‚·ÎÙËÚÔÂȉÒÓ, fiˆ˜ ›- «ÛȈËÏ¿» Ó· ·ÍÈÔÔÈÔ‡Ó ÙÔ ÂÚÈ‚¿ÏÏÔÓ ÙˆÓ Ì·ÎÚÔ- Ó·È Ô LPS Ù˘ E. coli. ™Â Û¯¤ÛË Ì ·˘ÙfiÓ ·ÚÔ˘ÛÈ¿- Ê¿ÁˆÓ Î·È ÙˆÓ ‰ÂÓ‰ÚÈÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ Ï·ıÚÔ‚ÈÒÓÔ- ˙ÂÈ ¯·ÌËÏfiÙÂÚË ·ÓÔÛÔÁÔÓÈÎfiÙËÙ· Î·È ÙÔÍÈÎfiÙËÙ·, ÁÂ- ÓÙ·˜16 (¶›Ó. 1). ÁÔÓfi˜ Ô˘ ÂӉ¯Ô̤ӈ˜ Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ÂÓ‰Ô΢ÙÙ¿- ™Â ÎÏÈÓÈÎfi ›‰Ô, ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ¯ÚfiÓÈ· ÚÈ· ÂÈ‚›ˆÛË ÙˆÓ ‚ÚÔ˘ÎÂÏÏÒÓ17,18. ¶ÈÔ Û˘ÁÎÂÎÚÈ̤ӷ, in vitro Û˘ÁÎÚÈÙÈΤ˜ ÌÂϤÙ˜ Û ·ÓıÚÒÈÓ· Ì·ÎÚÔÊ¿- ¶›Ó·Î·˜ 1. ∂›‰Ú·ÛË ÙˆÓ ‚ÚÔ˘ÎÂÏÏÒÓ ÛÙ· Ì·ÎÚÔÊ¿Á· (ªÊ) Á· η٤‰ÂÈÍ·Ó fiÙÈ ‰ÂÓ ‰ÈÂÁ›ÚÂÈ ÈÛ¯˘Ú¿ ÙËÓ ÔÍÂȉˆÙÈ- Î·È ÛÙ· ‰ÂÓ‰ÚÈÙÈο ·ÙÙ·Ú· (¢∫) ΋ ¤ÎÚËÍË, ÙËÓ ·Ú·ÁˆÁ‹ ÂÏ¢ı¤ÚˆÓ ÚÈ˙ÒÓ ·˙ÒÙÔ˘ – ∞Ó·ÛÙÔÏ‹ Ê·ÁÔÏ˘ÛÔÛˆÌÈ΋˜ Û‡ÓÙË͢ Î·È ÙËÓ ¤ÎÎÚÈÛË ÙˆÓ Ï˘ÛÔÛˆÌÈÎÒÓ ÂÓ˙‡ÌˆÓ, ÂÓÒ Ë – ¢È·ÌfiÚʈÛË Ê·ÁÔÛÒÌ·ÙÔ˜ ·Ó··Ú·ÁˆÁ‹˜ (·ÓÙÔ¯‹ ÛÙ· ›‰Ú·Û‹ ÙÔ˘ ÛÙËÓ ·Ú·ÁˆÁ‹ IL-1‚ Î·È TNF· Â›Ó·È Ï˘ÛÔÛˆÌÈο ¤Ó˙˘Ì·) ÌÈÎÚfiÙÂÚË. √ LPS ÙˆÓ ‚ÚÔ˘ÎÂÏÏÒÓ ‰ÂÓ ÂÓÂÚÁÔÔÈ› – ∫·Ù·ÛÙÔÏ‹ ·Ú·ÁˆÁ‹˜ TNF· Î·È IL-12 ÙËÓ ÂÓ·ÏÏ·ÎÙÈ΋ Ô‰fi ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ ÛÙÔÓ ·Ó- – ¶·ÚÂÌfi‰ÈÛË ·ÓÙÈÁÔÓÔ·ÚÔ˘Û›·Û˘ ıÚÒÈÓÔ ÔÚfi Î·È ÂÌÔ‰›˙ÂÈ ÙËÓ ÂÓ·fiıÂÛË ÙÔ˘ Û˘- – ¶·ÚÂÌfi‰ÈÛË Ù˘ TLR ÛËÌ·ÙÔ‰fiÙËÛ˘ ÌÏËÚÒÌ·ÙÔ˜ ÛÙËÓ ÂÈÊ¿ÓÂÈ· ÙˆÓ ‚·ÎÙËÚ›ˆÓ, ÂÓÒ – ∞Ó·ÛÙÔÏ‹ ˆÚ›Ì·ÓÛ˘ (¢∫) ·Ú¿ÏÏËÏ· ·ÛΛ ÚÔÛٷ٢ÙÈ΋ ‰Ú¿ÛË ¤Ó·ÓÙÈ ÔÈΛ- – ¶·ÚÂÌfi‰ÈÛË ·fiÙˆÛ˘ (ªÊ) 24 ÃÚfiÓȘ ÂÓ‰Ô΢ÙÙ¿ÚȘ ÏÔÈÌÒÍÂȘ: ÙÔ ·Ú¿‰ÂÈÁÌ· Ù˘ ‚ÚԢΤÏψÛ˘
¶›Ó·Î·˜ 2. ¢È·Ù·Ú·¯‹ Ù˘ ΢ÙÙ·ÚÈ΋˜ ·ÓÔÛ›·˜ Û ·ÛıÂÓ›˜ Ù¢ÙÈ΋˜ Th1 ·fiÎÚÈÛ˘, ÌÂÈÔÓÂÎÙÈ΋ ÂÓÂÚÁÔÔ›ËÛË Ì ¯ÚfiÓÈ· ‚ÚԢΤÏψÛË Ù˘ Ê˘ÛÈ΋˜ ¿Ì˘Ó·˜ ı· Ô‰ËÁ‹ÛÂÈ Û ‰È·Ù·Ú·¯‹ Ù˘ Th1 ΢ÙÙ·ÚÈ΋˜ ·¿ÓÙËÛ˘ Î·È ·ÓÂÚÁ›·29. ¶Ú¿ÁÌ·ÙÈ, - ↑ CD8+ Δ-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ - ↓ CD4+/CD8+ Δ-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ ex vivo Î·È in vitro ÌÂϤÙ˜ Û ·ÛıÂÓ›˜ Ì ·Ú·ÙÂÈ- - ·ÚÓËÙÈΤ˜ ‰ÂÚÌÔ·ÓÙȉڿÛÂȘ Û ‚·ÎÙËÚȷο ·ÓÙÈÁfiÓ· ÓfiÌÂÓË, ¯ÚfiÓÈ· ‚ÚԢΤÏψÛË, ‹ ηٿ ÙË ‰È¿ÚÎÂÈ· ÙˆÓ - ↓ ÈηÓfiÙËÙ·˜ ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ ÁÈ· ‚Ï·ÛÙÔ- ˘ÔÙÚÔÒÓ ¤¯Ô˘Ó ηٷ‰Â›ÍÂÈ fiÙÈ Ë ÔÚ›· Î·È Ë ÙÂÏÈ- Á¤ÓÂÛË Î‹ ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙÔÓ ·ÚÈıÌfi Î·È (in vitro ‰È¤ÁÂÚÛË Ì PHA ‹ ‚ÚÔ˘ÎÂÏÏÈο ·ÓÙÈÁfiÓ·) ÙË ÏÂÈÙÔ˘ÚÁÈ΋ ÈηÓfiÙËÙ· ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ÏÂÌÊÔ΢Ù- ↓ - Ù˘ ¤ÎÊÚ·Û˘ CD69 ÛÙ· Δ-ÏÂÌÊÔ·ÙÙ·Ú· Ù¿ÚˆÓ. √È ·ÛıÂÓ›˜ Ì ¯ÚfiÓÈ· ‚ÚԢΤÏψÛË ÂÌÊ·Ó›- ↓ - Û‡ÓıÂÛ˘ Î·È ¤ÎÎÚÈÛ˘ Th1 ΢ÙÙ·ÚÔÎÈÓÒÓ (IFNÁ Î·È IL-2) ˙Ô˘Ó ·Ó·Ú΋ Th1 ·fiÎÚÈÛË9,22,30-32 (¶›Ó. 2). - ↓ CD3+/IFNÁ+ Δ-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ - ↓ CD3+/IL13+ Δ-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ (ÛÙÚÔÊ‹ ·fi Th1 Û Th2 Δ· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ¤¯ÂÈ ÔÏÔÎÏËÚˆı› Ë ¯·ÚÙÔ- ·fiÎÚÈÛË) ÁÚ¿ÊËÛË ÙÔ˘ ÁÂÓÒÌ·ÙÔ˜ ÙˆÓ ÂÚÈÛÛfiÙÂÚˆÓ ÂȉÒÓ - ↓ CD4+/CD25+ Δ-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ ‚ÚԢΤÏÏ·˜ Î·È ¤¯Ô˘Ó ·Ó¢ÚÂı› ‰È¿ÊÔÚ· ÚˆÙÂ˚ÓÈ- ο Û˘ÛÙ‹Ì·Ù· (VirB, BvrR/S, SOD, dnaK, PurE/AroC, PrpA) Ù· ÔÔ›· ¢ı‡ÓÔÓÙ·È ÁÈ· ÙË ‰È·ÌfiÚʈÛË Î·- ‚ÚԢΤÏψÛË ¤¯ÂÈ ÂÚÈÁÚ·Ê› ÂÌ̤ÓÔ˘Û· ‰È·Ù·Ú·¯‹ Ù¿ÏÏËÏˆÓ Û˘ÓıËÎÒÓ ÂÈ‚›ˆÛ‹˜ ÙÔ˘˜ ÛÙ· Ê·ÁÔÛÒÌ·- Ù˘ Ê·ÁÔ΢ÙÙ¿ÚˆÛ˘, Ù˘ ¯ËÌÂÈÔÙ·Í›·˜ Î·È ÙÔ˘ ‰Â›- Ù·. ªÂÙ·ÏÏ¿ÍÂȘ ÛÙ· ÁÔÓ›‰È·, Ô˘ Έ‰ÈÎÔÔÈÔ‡Ó ÙȘ ÎÙË ·Ó·ÛÙÔÏ‹˜ ÌÂÙ·Ó¿ÛÙ¢Û˘ ÙˆÓ Ï¢ÎÔ΢ÙÙ¿ÚˆÓ. ·Ú·¿Óˆ ÚˆÙ½Ó˜, Ô‰ËÁÔ‡Ó Û ÛÙÂϤ¯Ë Ì ÂÍ·- √È ·Ú·¿Óˆ ·Ú¿ÌÂÙÚÔÈ ‚ÂÏÙÈÒÓÔÓÙ·È ‹ ·Ôηı›- ÛıÂÓË̤ÓË ÏÔÈÌÔÁfiÓÔ ‰‡Ó·ÌË Î·È ·‰˘Ó·Ì›· ·Ú·ÛÈ- ÛÙ·ÓÙ·È ÌÂÙ¿ ·fi ÙË ¯ÔÚ‹ÁËÛË ·ÓÔÛÔÂÓÈÛ¯˘ÙÈ΋˜ ÙÈÛÌÔ‡ ÛÙ· Ì·ÎÚÔÊ¿Á·33,34. ·ÁˆÁ‹˜ fiˆ˜ Ï‚·ÌÈ˙fiÏ˘, ·ÛÎÔÚ‚ÈÎÔ‡ ÔͤԘ, IFN·, ∞fi ÙËÓ ¿ÏÏË ÌÂÚÈ¿, ·ÓÔÛÔÁÂÓÂÙÈΤ˜ ÌÂϤÙ˜ Û ‚·ÎÙËÚÈ·ÎÒÓ Âί˘ÏÈÛÌ¿ÙˆÓ Î·È ÈÛÔÚÈÓÔÛ›Ó˘, Ì·˙› ‚ÚÔ˘ÎÂÏÏÈÎÔ‡˜ ·ÛıÂÓ›˜ ¤¯Ô˘Ó Û˘Û¯ÂÙ›ÛÂÈ ÁÂÓÂÙÈ- Ì ÙËÓ ÎÏ·ÛÈ΋ ·ÓÙÈÌÈÎÚԂȷ΋ ıÂڷ›·9,20. ÎÔ‡˜ ÔÏ˘ÌÔÚÊÈÛÌÔ‡˜ ‹ ÁÔÓȉȷΤ˜ ÌÂÙ·ÏÏ¿ÍÂȘ Ì ¢Â‰Ô̤ÓÔ˘ fiÙÈ Ë Ê˘ÛÈ΋ ·ÓÔÛ›· Â›Ó·È ÛËÌ·ÓÙÈ΋ ÙËÓ ÚԉȿıÂÛË ‹ ·ÓÙÔ¯‹ ÛÙË ÓfiÛÔ Î·ıÒ˜ Î·È Ì ÙȘ ÁÈ· ÙËÓ ·Ó¿Ù˘ÍË ¤ÁηÈÚ· ÌÈ·˜ ·ÚÎÔ‡˜, ÚÔÛÙ·- ‰È¿ÊÔÚ˜ ÌÔÚʤ˜/ÂÈÏÔΤ˜ Ù˘ ÓfiÛÔ˘ (¶›Ó. 3).
¶›Ó·Î·˜ 3. ∞ÓÔÛÔÁÂÓÂÙÈ΋ Ù˘ ·ÓıÚÒÈÓ˘ ‚ÚԢΤÏψÛ˘ (2000-2008)
°ÔÓ›‰ÈÔ ∞ÛıÂÓ›˜/ p ¶ÚԤϢÛË μÈ‚ÏÈÔÁÚ·ÊÈ΋ ·Ó·ÊÔÚ¿ £¤ÛË ª¿ÚÙ˘Ú˜ TNF· ÚÔ·ÁˆÁ¤·˜ 59/160 πÛ·Ó›· Caballero et al, (-308).2 s Clin Exp Immunol 2000 (-238) ns HLA DRB1, DQB1 ns CCR5 185/141 ∂ÏÏ¿‰· Skendros et al, ¢32 ÌÂÙ¿ÏÏ·ÍË ns Scand J Infect Dis 2002 NOS2 ÚÔ·ÁˆÁ¤·˜ 85/100 πÛ·Ó›· Orozco et al, TAAAn ÌÈÎÚÔ‰ÔÚ˘ÊÔÚÈÎfi ns Microbes Infect 2003 CCTTTn ÌÈÎÚÔ‰ÔÚ˘ÊÔÚÈÎfi ns IFNÁ 83/101 πÛ·Ó›· Bravo et al, (+874) A/A s Eur J Immunogenet 2003 IL-10 (-1082, -819, -592) ns HLA 57 (23)/73 πÛ·Ó›· Bravo et al, B39 s* J Rheumatol 2003 NRAMP1 65/89 ns πÛ·Ó›· Bravo et al, Microbes Infect 2005 TLR4 198/111 πÚ¿Ó Rezazadeh et al, A896G (Asp299Gly) A/G s** J Infect 2006 ¶. ™Î¤Ó‰ÚÔ˜ 25
IL-4 ÚÔ·ÁˆÁ¤·˜ 282/163 πÚ¿Ó Rezazadeh et al, (-590) C/T s Scand J Infect Dis 2006 CD14 ÚÔ·ÁˆÁ¤·˜ 228/129 πÚ¿Ó Haidari et al, (-159) T/T s (s*) Immunol Invest 2006 L-selectin 374/245 πÚ¿Ó Rafiei et al, Phe206Leu s (s***) J Med Microbiol 2006 TNF· 47/166 πÚ¿Ó Davoudi et al, GG/GG s Int J Immunogenet 2006 IFNÁ Î·È IL-2 ns TGF‚1 (↑) 425/213 πÚ¿Ó Rafiei et al, 10 C, 25 G (CG/TG) s Clin Microbiol Infect 2007 IL10, IL-6 (↑) 40/50 s ΔÔ˘ÚΛ· Budak et al, IFNÁ, TGF‚ Î·È TNF· ns Cytokine 2007 IFNÁ 195/91 πÚ¿Ó Rasouli and Kiany, (+874) A/A s Cytokine 2007 IL-4 ÚÔ·ÁˆÁ¤·˜ (-590) C/C s**** IFNÁT/IL-4C s**** IFNÁTT/IL-4CC s**** MICA 114/121 πÛ·Ó›· Bravo et al, A4 s**** Tissue Antigens 2007 A5 s***** E-selectin 258/193 πÚ¿Ó Rafiei et al, Ser128Arg s Infect Genet Evol 2007 FcÁRII· 150/125 πÚ¿Ó Hashemi et al, H131, R131 ns Jpn J Infect Dis 2007 IL-10 190/81 πÚ¿Ó Rasouli et al, -1082(G/A) ns Iran J Immunol 2008 -819(T/C) C s -592(A/C) C s TGF‚1, 82/102 πÛ·Ó›· Bravo et al, 10 C, 25 G (CG/TG) s (s*****) Cytokine 2008 IL-6 ÚÔ·ÁˆÁ¤·˜ (-174) ns * Ì˘ÔÛÎÂÏÂÙÈΤ˜ ÂΉËÏÒÛÂȘ, ** ¿Ó‰Ú˜, ***˘ÔÙÚÔ‹, **** ·ÓÙÔ¯‹, *****ÚԉȿıÂÛË ÁÈ· ÂÛÙȷ΋ ÓfiÛÔ s= ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈÎfi, ns= ÌË ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈÎfi
™˘ÌÂÚ·ÛÌ·ÙÈο Ë ÌÂϤÙË Ù˘ ·ÓÔÛȷ΋˜ ·fi- the bacterial pathogens. In: Kaufmann SHE, Sher A, Ah- ÎÚÈÛ˘ ‚ÔËı¿ÂÈ ÛÙËÓ Î·Ï‡ÙÂÚË Î·Ù·ÓfiËÛË Î·È ·ÓÙÈ- med R (eds). Immunology of Infectious Diseases. Wa- ÌÂÙÒÈÛË ÙˆÓ ‰È¿ÊÔÚˆÓ ÎÏÈÓÈÎÒÓ ÌÔÚÊÒÓ Ù˘ ‚ÚÔ˘- shington DC: ASM Press, 2002: 5-23. ΤÏψÛ˘, Ô˘ Î˘Ì·›ÓÔÓÙ·È ·fi ÙËÓ Ù˘È΋ ÔÍ›· ¤ˆ˜ 3. Ismail N, Olano JP, Feng HM, Walker DH. Current status of immune mechanisms of killing of intracellular microor- ÙËÓ ¿Ù˘Ë ¯ÚfiÓÈ· ÓfiÛÔ. ganisms. FEMS Microbiol Lett. 2002; 207: 111-120. 4. Janeway CA Jr, Medzhitov R. Innate immune recognition. μÈ‚ÏÈÔÁÚ·Ê›· Annu Rev Immunol 2002; 20: 197-216. 1. Collins HL, Kaufmann SHE. Immune responses to intra- 5. ™Î¤Ó‰ÚÔ˜ ¶. ∞ÓÔÛȷ΋ ·¿ÓÙËÛË Û ÂÓ‰Ô΢ÙÙ¿ÚÈ· ÌÈÎÚfi- cellular bacteria. In: Rich RR, Fleisher TA, Shearer WT, ‚È·. ™ÙÔ: ∂ȉÈ΋ ·ÓÔÛ›·. ™ÂÌÈÓ¿ÚÈÔ ∞ÓÔÛÔÏÔÁ›·˜, 20Ô˜ Kotzin BL, Schroeder HW Jr (eds). Clinical Immunology. ·ÎÏÔ˜, 2Ô Ì¤ÚÔ˜. ∞ı‹Ó·: ∂ÏÏËÓÈ΋ ∂Ù·ÈÚ›· ∞ÓÔÛÔÏÔ- Principles and Practice. 2nd edition. London: Mosby, Á›·˜, 2004: 180-186. 2001: 26.1-26.16. 6. Ottenhoff TH, Bevan MJ. Host-pathogen interactions. Curr 2. Kuhn M, Goebel W, Philpott DJ, Sansonetti PJ. Overview of Opin Immunol. 2004; 16: 439-442. 26 ÃÚfiÓȘ ÂÓ‰Ô΢ÙÙ¿ÚȘ ÏÔÈÌÒÍÂȘ: ÙÔ ·Ú¿‰ÂÈÁÌ· Ù˘ ‚ÚԢΤÏψÛ˘
7. Pappas G, Papadimitriou P, Akritidis N, Christou L, Tsianos lymphocytes expressing CD25 and CD28 after Es- EV. The new global map of human brucellosis. Lancet cherichia coli LPS stimulation of PHA-cultured PBMCs. Infect Dis. 2006; 6: 91-9. Clin Dev Immunol. 2008; 2008: 327-46. 8. Pappas G, Akritidis N, Bosilkovski M, Tsianos E. Brucellosis. 23. Jubier-Maurin V, Boigegrain RA, Cloeckaert A, et al. Major N Engl J Med. 2005; 352: 2325-6. outer membrane protein Omp25 of Brucella suis is in- 9. Boura P, Skendros P, Kountouras J, Zacharioudaki E, Tsapas volved in inhibition of tumor necrosis factor alpha pro- T. Effect of bacterial extracts on the immunologic profile duction during infection of human macrophages. Infect in chronic relapsing brucellosis patients. Int J Immuno- Immun. 2001; 69: 4823-30. pathol Pharmacol. 1999; 12: 103-11. 24. Barrionuevo P, Cassataro J, Delpino MV, et al. Brucella 10. Berbari EF, Wilson WR. Brucella, Francisella, Pasteurella, abortus inhibits major histocompatibility complex class II Yersinia and HACEK. In: Wilson WR, Sande MA, editors. expression and antigen processing through interleukin-6 Current Diagnosis & Treatment in Infectious Diseases. secretion via Toll-like receptor 2. Infect Immun. 2008; New York, NY, USA: McGraw-Hill, 2001: 630–3. 76: 250-62. 11. de Bagues Maria-Pilar J, Dudal S, Dornand J, Gross A. Cel- 25. Cirl C, Wieser A, Yadav M, et al. Subversion of Toll-like lular bioterrorism: how Brucella corrupts macrophage receptor signaling by a unique family of bacterial Toll/in- physiology to promote invasion and proliferation. Clin terleukin-1 receptor domain-containing proteins. Nat Immunol. 2005; 114: 227-38. Med. 2008; 14: 399-406. 12. Baldwin CL, Goenka R. Host immune responses to the in- 26. Salcedo SP, Marchesini MI, Lelouard H, et al. Brucella con- tracellular bacteria Brucella: does the bacteria instruct trol of dendritic cell maturation is dependent on the TIR- the host to facilitate chronic infection? Crit Rev Immunol. containing protein Btp1. PLoS Pathog. 2008; 4: e21. 2006; 26: 407-42. 27. Billard E, Cazevieille C, Dornand J, Gross A. High suscepti- 13. Yagupsky P, Baron EJ. Laboratory exposures to brucellae bility of human dendritic cells to invasion by the intracel- and implications for bioterrorism. Emerg Infect Dis. lular pathogens Brucella suis, B. abortus, and B. meliten- 2005; 11: 1180-5. sis. Infect Immun. 2005; 73: 8418-24. 14. Dornand J, Gross A, Lafont V, Liautard J, Oliaro J, Liautard 28. Billard E, Dornand J, Gross A. Brucella suis prevents human JP. The innate immune response against Brucella in hu- dendritic cell maturation and antigen presentation thro- mans. Vet Microbiol. 2002; 90: 383-394. ugh regulation of tumor necrosis factor alpha secretion. 15. Golding B, Scott DE, Scharf O, et al. Immunity and prote- Infect Immun. 2007; 75: 4980-9. ction against Brucella abortus. Microbes Infect. 2001; 3: 29. Schnare M, Barton GM, Holt AC, Takeda K, Akira S, Med- 43-8. zhitov R. Toll like receptors control activation of adapti- 16. Barquero-Calvo E, Chaves-Olarte E, Weiss DS, et al. Bru- ve immune responses. Nat Immunol. 2001; 2: 947-50. cella abortus uses a stealthy strategy to avoid activation 30. Giambartolomei GH, Delpino MV, Cahanovich ME, et al. of the innate immune system during the onset of infe- Diminished production of T helper 1 cytokines correla- ction. PLoS ONE. 2007; 2: e631. tes with T cell unresponsiveness to Brucella cytoplasmic 17. Lapaque N, Moriyon I, Moreno E, Gorvel JP. Brucella proteins in chronic human brucellosis. J Infect Dis. 2002; lipopolysaccharide acts as a virulence factor. Curr Opin 186: 252-9. Microbiol. 2005; 8: 60-6. 31. Rafiei A, Ardestani SK, Kariminia A, Keyhani A, Mohraz M, 18. Cardoso PG, Macedo GC, Azevedo V, Oliveira SC. Bru- Amirkhani A. Dominant Th1 cytokine production in ear- cella spp noncanonical LPS: structure, biosynthesis, and ly onset of human brucellosis followed by switching to- interaction with host immune system. Microb Cell Fact. wards Th2 along prolongation of disease. J Infect. 2006; 2006; 5: 13. 53: 315-24. 19. Kariminia A, Kavoossy G, Khatami S, Zowghi E, Ardestani 32. Skendros P, Boura P, Chrisagis D, Raptopoulou-Gigi M. SK. Study of interleukin-10 and interleukin-12 produ- Diminished percentage of CD4+ T-lymphocytes expres- ctions in response to lipopolysaccharides extracted from sing interleukine-2 receptor alpha in chronic brucellosis. two different Brucella strains. Comp Immunol Microbiol J Infect. 2007; 54: 192-7. Infect Dis. 2002; 25: 85-93. 33. Rajashekara G, Eskra L, Mathison A, et al. Brucella: functio- 20. ™Î¤Ó‰ÚÔ˜ ¶. ∞ÓÔÛȷ΋ ·fiÎÚÈÛË Î·È Û˘Ó‰È¤ÁÂÚÛË ÛÙË nal genomics and host-pathogen interactions. Anim ‚ÚԢΤÏψÛË. ¢È‰·ÎÙÔÚÈ΋ ‰È·ÙÚÈ‚‹. ∞ÚÈÛÙÔÙ¤ÏÂÈÔ ¶·- Health Res Rev. 2006; 7: 1-11. ÓÂÈÛÙ‹ÌÈÔ £ÂÛÛ·ÏÔӛ΢, 2006. 34. Celli J. Surviving inside a macrophage: the many ways of 21. Skendros P, Boura P, Kamaria F, Raptopoulou-Gigi M. Brucella. Res Microbiol. 2006; 157: 93-8. CD80/CD28 co-stimulation in human brucellosis. Clin Exp Immunol. 2006; 146: 400-8. 22. Skendros P, Sarantopoulos A, Tselios K, Boura P. Chronic ∞ÏÏËÏÔÁÚ·Ê›·: brucellosis patients retain low frequency of CD4+ T- E-mail: [email protected] ∞ÓÔÛÔÏÔÁ›· Ïԛ̈͢
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2009; 1: 27 – 30
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ÙˆÓ ÂÌ‚ÔÏ›ˆÓ ÛÙ· ‡„Ë. ¶ÈÛÙ‡ÂÙ·È fiÙÈ fiÙ·Ó ·Ú¯›ÛÂÈ Ë ÛÈ·Îfi Û‡ÛÙËÌ·10,11. √È Ô˘Û›Â˜ ·˘Ù¤˜ ÏÂÈÙÔ˘ÚÁÔ‡Ó Â˘Ú›· ¯Ú‹ÛË Ù˘ Ó¤·˜ Ù¯ÓÔÏÔÁ›·˜ ·Ú·Û΢‹˜ ÂÌ- fiˆ˜ Ô ‰Ô‡ÚÂÈÔ˜ ›Ô˜. ™ÙȘ Ô˘Û›Â˜ ·˘Ù¤˜ ·Ó‹ÎÔ˘Ó ‚ÔÏ›ˆÓ, ı· ÂÏ·ÙÙˆıÔ‡Ó ÔÈ ÙÈ̤˜ ÙˆÓ ÂÌ‚ÔÏ›ˆÓ6. Ù· ÚԂȈÙÈο, Ô˘Û›Â˜ ÔÈ Ôԛ˜ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È °È· Ó· ˘¿Ú¯Ô˘Ó ·ÔÙÂϤÛÌ·Ù· ·fi ÙÔÓ ÂÌ‚Ô- ÁÈ· ÔÚÈṲ̂ӷ ηÚÎÈÓÈο ÂÌ‚fiÏÈ·. ÏÈ·ÛÌfi ¤Ó·ÓÙÈ ÏÔÈÌÒ‰Ô˘˜ ÓÔÛ‹Ì·ÙÔ˜ ı· Ú¤ÂÈ Ë ÂÌ- ∏ ‰›ÎËÓ ÂÈÛÓÔÒÓ ‹ ·fi ÙËÓ Ì‡ÙË ¯ÔÚ‹ÁËÛË ÙˆÓ ‚ÔÏÈ·ÛÙÈ΋ Î¿Ï˘„Ë Ó· Â›Ó·È Â·Ú΋˜. ÂÌ‚ÔÏ›ˆÓ ¤¯ÂÈ ÔÏÏ¿ ÚÔ‚Ï‹Ì·Ù·12,13. ΔÔ ‚·ÛÈÎfiÙÂÚÔ ∏ ·Ú΋˜ Î¿Ï˘„Ë ÂÈÙ˘Á¯¿ÓÂÙ·È Ì ÙÔ ¯·ÌËÏfi Úfi‚ÏËÌ· Â›Ó·È Ë ·‰Ú·ÓÔÔ›ËÛË ‹ ηٷÛÙÚÔÊ‹ Ù˘ ÎfiÛÙÔ˜ ÙˆÓ ÂÌ‚ÔÏ›ˆÓ, ÁÈ· Ó· ÌÔÚ› ÙÔ ÂÌ‚fiÏÈÔ Ó· ÚˆÙ½Ó˘ Ô˘ ÂÚȤ¯Ô˘Ó Ù· ÂÌ‚fiÏÈ· Ì ·ÔÙ¤ÏÂÛÌ· ‰È·ÙÂı› ·fi fiÏ· Ù· ·ÛÊ·ÏÈÛÙÈο Ù·Ì›· ‰ˆÚ¿Ó. ∂›- ·˘Ù¿ Ó· ηı›ÛÙ·ÓÙ·È ·ÓÂÓÂÚÁ¿. ∏ ¯ÔÚ‹ÁËÛË ·fi ÙÔ˘ Û˘ Ë ÂÌ‚ÔÏÈ·ÛÙÈ΋ Î¿Ï˘„Ë ‚ÂÏÙÈÒÓÂÙ·È Ì ÙËÓ Î·ıȤ- ÔÊı·ÏÌÔ‡ ÚÔηÏ› ‰·ÎÚ‡ÚÚÔÈ· Î·È ÌÔÚ› Ôχ ÚˆÛË ÙˆÓ ‚È‚ÏÈ·Ú›ˆÓ ˘Á›·˜, ÙËÓ Î·Ï‹ ÂÓË̤ڈÛË Û ÁÚ‹ÁÔÚ· Ó· ·ÔÌ·ÎÚ˘Óı› Ë ·ÓÙÈÁÔÓÈ΋ Ô˘Û›· ÙÔ˘ ÂÌ- ı¤Ì·Ù· ÈÛÔÚÚÔ›·˜ ÎÈÓ‰‡ÓÔ˘-ˆÊ¤ÏÂÈ·˜ ÙˆÓ ÂÌ‚ÔÏ›ˆÓ, ‚ÔÏ›Ô˘ ÚÈÓ ÚÔÏ¿‚ÂÈ Ó· ·ÔÚÚÔÊËı›. ÙËÓ ÂÓË̤ڈÛË ÙˆÓ ÏÂÈÙÔ˘ÚÁÒÓ ˘Á›·˜ ÁÈ· Ù· Ó¤· ÂÌ- ∏ ·fi ÙÔ˘ ÔÚıÔ‡ ¯ÔÚ‹ÁËÛË ÙÔ˘ ÂÌ‚ÔÏ›Ô˘ ‰ÂÓ ‚ÔÏÈ·ÛÙÈο ÚÔÁÚ¿ÌÌ·Ù· Î·È ÙËÓ Â·Ú΋ Û˘Ó¯È˙fiÌÂ- ¯ÚËÛÈÌÔÔÈÂ›Ù·È ‰ÈfiÙÈ Ë ·ÔÚÚfiÊËÛË ‰ÂÓ Â›Ó·È ÈηÓÔ- ÓË Âη›‰Â˘ÛË, ÙËÓ Â¿ÚÎÂÈ· ÚÔÛˆÈÎÔ‡ Ô˘ ·Û¯Ô- ÔÈËÙÈ΋ Î·È ‰ÈfiÙÈ ·ÚÎÂÙ¤˜ ¯ÒÚ˜, ÁÈ· ıÚËÛ΢ÙÈÎÔ‡˜ ÏÔ‡ÓÙ·È Ì ÙÔ˘˜ ÂÌ‚ÔÏÈ·ÛÌÔ‡˜ Î·È Ê˘ÛÈο Ì ÙËÓ Â¿Ú- ÏfiÁÔ˘˜,, ‰ÂÓ ‰¤¯ÔÓÙ·È ÙÔÓ ÙÚfiÔ ·˘Ùfi ¯ÔÚ‹ÁËÛ˘ ÙˆÓ ÎÂÈ· ÙˆÓ ÂÌ‚ÔÏ›ˆÓ1,3,8. ÂÌ‚ÔÏ›ˆÓ10. ŒÓ·˜ ÛËÌ·ÓÙÈÎfi˜ ·Ú¿ÁˆÓ ÁÈ· ÙËÓ ÂÌ‚ÔÏÈ·ÛÙÈ΋ ∏ ÌÂÁ·Ï‡ÙÂÚË ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙˆÓ ÂÌ‚ÔÏ›ˆÓ Î¿Ï˘„Ë Â›Ó·È Ë Â‡ÎÔÏË ÌÂÙ·ÊÔÚ¿, ‰È·ÓÔÌ‹ Î·È Ô Â‡ÎÔ- Â›Ó·È Û˘Ó˘Ê·Ṳ̂ÓË Ì ÙË Ì·ÎÚÔ¯ÚfiÓÈ· Î·È ÈÛ¯˘Ú‹ ·ÓÔ- ÏÔ˜ ÙÚfiÔ˜ ¯ÔÚ‹ÁËÛ˘ ÙÔ˘ ÂÌ‚ÔÏ›Ô˘3,9,10. ŒÙÛÈ ÏÔÈfiÓ, Û›·14,15. Δ· ÂÌ‚fiÏÈ· Ì ÙË ÌÂÁ·Ï‡ÙÂÚË ·ÔÙÂÏÂÛÌ·ÙÈ- Ù· ÂÌ‚fiÏÈ· Ô˘ Â›Ó·È ÛÙ·ıÂÚ¿ ÛÙË ıÂÚÌÔÎÚ·Û›· ‰ˆ- ÎfiÙËÙ· Â›Ó·È Ù· ÂÌ‚fiÏÈ· Ô˘ ÂÚȤ¯Ô˘Ó ˙ˆÓÙ·Ófi ÂÍ·- Ì·Ù›Ô˘ Î·È ‰ÂÓ ¯ÚÂÈ¿˙ÔÓÙ·È ÂȉÈΤ˜ Û˘Óı‹Î˜ ÌÂÙ·ÊÔ- ÛıÂÓË̤ÓÔ ÌÈÎÚÔÔÚÁ·ÓÈÛÌfi. Ú¿˜ ÌÔÚ› Ó· ÌÂÙ·ÊÂÚıÔ‡Ó Â‡ÎÔÏ· Î·È ÁÚ‹ÁÔÚ· Û √È ÂÚ¢ÓËÙ¤˜, ÛÙ· ÂÌ‚fiÏÈ· Ô˘ ÂÚȤ¯Ô˘Ó ÓÂ- fiÏ· Ù· ̤ÚË Ù˘ Á˘. ÎÚÔ‡˜ ÌÈÎÚÔÔÚÁ·ÓÈÛÌÔ‡˜, ÚÔ˚fiÓÙ· ÌÈÎÚÔÔÚÁ·ÓÈÛÌÒÓ, ¶ÔÏÏ¿ ÂηÙÔÌ̇ÚÈ· ‰fiÛÂˆÓ ÂÌ‚ÔÏ›Ô˘ ·ÔÚÚ›- ‹ ÚˆÙ½Ó˜ Ù˘ ÌÂÌ‚Ú¿Ó˘ ÙÔ˘˜ ÚÔÛı¤ÙÔ˘Ó Ô˘Û›Â˜ ÙÔÓÙ·È Î·È Î·Ù·ÛÙÚ¤ÊÔÓÙ·È ˆ˜ ·Î·Ù¿ÏÏËÏ· οı ¯Úfi- Ô˘ ηÏÔ‡ÓÙ·È ·ÓÔÛÔÂÓÈÛ¯˘ÙÈΤ˜15,16. √È ·ÓÔÛÔÂÓÈÛ¯˘- ÓÔ, ·Ú¿ ÙË ÌÂÁ¿ÏË ¯ÚËÛÈÌfiÙËÙ¿ ÙÔ˘˜. ∞˘Ùfi Û˘Ì‚·›ÓÂÈ ÙÈΤ˜ ·˘Ù¤˜ Ô˘Û›Â˜ ÚÔηÏÔ‡Ó Â˘ÓÔ˚Τ˜ ÙÚÔÔÔÈ‹ÛÂȘ ‰ÈfiÙÈ ÔÈ ÚÔ·Ó·ÊÂÚı›Û˜ ‰fiÛÂȘ ıˆÚÔ‡ÓÙ·È ˆ˜ ·ÓÂ- Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙË ‰È¿ÚÎÂÈ· ·Ú·ÌÔÓ‹˜ ÙÔ˘ ·ÓÙÈÁfi- ÓÂÚÁ›˜. √È ÂÚ¢ÓËÙ¤˜ ˘fiÛ¯ÔÓÙ·È fiÙÈ ÙËÓ ÂfiÌÂÓË ‰Â- ÓÔ˘ ÛÙÔ ·ÓÔÛÈ·Îfi Û‡ÛÙËÌ·, Ì ÙËÓ ÚfiÏË„Ë ÙÔ˘ ·ÓÙÈ- ηÂÙ›· ı· ˘¿Ú¯ÂÈ ÂȉÈÎfi˜ ‰Â›ÎÙ˘ ¿ӈ ÛÙËÓ ÂÙÈΤٷ ÁfiÓÔ˘ ·fi Ù· Ì·ÎÚÔÊ¿Á· ·ÙÙ·Ú·, Ì ÙË Û˘ÚÚÔ‹ ÙˆÓ ÙÔ˘ ÂÌ‚ÔÏ›Ô˘, Ô ÔÔ›Ô˜ ı· ˘Ô‰ÂÈÎÓ‡ÂÈ ÙËÓ Î·Ù·ÏÏË- Ì·ÎÚÔÊ¿ÁˆÓ ÛÙÔ ÛËÌÂ›Ô Ù˘ ¯ÔÚ‹ÁËÛ˘ ÙÔ˘ ÂÌ‚ÔÏ›- ÏfiÙËÙ· ÙÔ˘ ÂÌ‚ÔÏ›Ô˘. Ô˘, ÙËÓ ·Ú·ÁˆÁ‹ ΢ÙÙ·ÚÔÎÈÓÒÓ Ô˘ ÂÓÂÚÁÔÔÈÔ‡Ó Ù· Δ· ÂÌ‚fiÏÈ· Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Û‹ÌÂÚ· ÛÙËÓ Î‡ÙÙ·Ú· ÙÔ˘ ·ÓÔÛÔÔÈËÙÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜. ÏÂÈÔÓfiÙËÙ¿ ÙÔ˘˜ ¯ÔÚËÁÔ‡ÓÙ·È ·ÚÂÓÙÂÚÈÎÒ˜, Ú¿ÁÌ· ∂›Ó·È ÁÓˆÛÙfi fiÙÈ Ù· ÂÚÈÛÛfiÙÂÚ· ÂÌ‚fiÏÈ· ÂÓÂÚÁÔ- Ô˘ ÛËÌ·›ÓÂÈ fiÙÈ Ú¤ÂÈ Ó· ˘¿Ú¯Ô˘Ó ÂȉÈο ÂÎ·È‰Â˘- ÔÈÔ‡Ó ÙËÓ Th2 ·ÓÔÛȷ΋ ·¿ÓÙËÛË Ë ÔÔ›· ‰ÂÓ ·- ̤ӷ ¿ÙÔÌ· ÁÈ· ÙÔ˘˜ ÂÌ‚ÔÏÈ·ÛÌÔ‡˜, ·ÔÛÙÂÈڈ̤ÓË Ú¤¯ÂÈ ÈÛ¯˘Ú‹ ·ÓÔÛ›·. πÛ¯˘Ú‹ ·ÓÔÛ›· ÚÔηÏÔ‡Ó Ù· ÂÌ- Û‡ÚÚÈÁÁ· Î·È ‚ÂÏfiÓË, ¯ˆÚ›˜ Ê˘ÛÈο Ó· ·ÁÓÔÂ›Ù·È ÙÔ ¿Ï- ‚fiÏÈ· Ô˘ ÂÓÂÚÁÔÔÈÔ‡Ó ÙËÓ Th1·ÓÔÛȷ΋ ·¿ÓÙËÛË ÁÔ˜ ·fi ÙËÓ ¤ÓÂÛË. fiˆ˜ ÙÔ ÂÌ‚fiÏÈÔ ÈÏ·Ú¿˜ – ÂÚ˘ıÚ¿˜ – ·ÚˆÙ›ÙȉԘ. °È· ™‹ÌÂÚ· Á›ÓÂÙ·È ÚÔÛ¿ıÂÈ· ‰È¿ıÂÛ˘ ÙˆÓ ÂÌ‚Ô- ·˘ÙfiÓ ÙÔÓ ÏfiÁÔ ÔÈ ÂÚ¢ÓËÙ¤˜ ÚÔÛ·ıÔ‡Ó ÔÈ ·ÓÔÛÔÂ- Ï›ˆÓ ·fi ¿ÏϘ Ô‰Ô‡˜ fiˆ˜ ·fi ÙÔ˘ ÛÙfiÌ·ÙÔ˜, ÂÓ‰Ô- ÓÈÛ¯˘ÙÈΤ˜ Ô˘Û›Â˜ ÙˆÓ ÂÌ‚ÔÏ›ˆÓ Ó· ÚÔηϤÛÔ˘Ó ÙËÓ ÚÈÓÈο, ·fi ÙÔ˘ ÔÊı·ÏÌÔ‡, Ì ÂÈÛÓÔ¤˜ Î·È ·fi ÙÔ˘ ÂÓÂÚÁÔÔ›ËÛË Ù˘ Th1 ·ÓÔÛȷ΋˜ ·¿ÓÙËÛ˘. ÃÚËÛÈ- 10,11 ÔÚıÔ‡ . ÌÔÔÈÔ‡Ó ÏÔÈfiÓ ‰È¿ÊÔÚ˜ ¯ËÌÈΤ˜ Ô˘Û›Â˜ – Û˘ÓıÂÙÈ- ∏ ¯ÔÚ‹ÁËÛË ÂÌ‚ÔÏ›ˆÓ ·fi ÙÔ˘ ÛÙfiÌ·ÙÔ˜ ¤¯ÂÈ Î¿ ÌfiÚÈ· (ÌÈÎÚÔۈ̷ٛ‰È·, Ó·ÓÔۈ̷ٛ‰È·, ÈÔÛÒÌ·Ù·, ÔÏϤ˜ ‰˘ÛÎÔϛ˜ ‰ÈfiÙÈ ˆ˜ ÁÓˆÛÙfiÓ Ù· ÂÌ‚fiÏÈ· Â- ÚˆÙÂÔÛÒÌ·Ù· Î.¿.) Î·È Ê˘ÛÈο ÌfiÚÈ· fiˆ˜ ‚ÈÔÏÔÁÈο ÚȤ¯Ô˘Ó ÚˆÙ½Ó˜ ÔÈ Ôԛ˜ ·Ó·ÁÓˆÚ›˙ÔÓÙ·È ·fi ÙÔÓ ÌfiÚÈ· (ILs, HSP60) Î·È ‰Ô̤˜ ÙˆÓ ÌÈÎÚÔÔÚÁ·ÓÈÛÌÒÓ ‚ÏÂÓÓÔÁfiÓÔ ÙÔ˘ Á·ÛÙÚÂÓÙÂÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ (°∂™) Û¯ÂÙÈ˙fiÌÂÓ˜ Ì ·ıÔÁÔÓÈÎfiÙËÙ· (PAMPs)1,3,17. Î·È ·ÔÚÚÔÊÒÓÙ·È ¯ˆÚ›˜ Ó· ·ÚÂÌ‚·›ÓÂÈ ÙÔ ·ÓÔÛÈ·- Îfi Û‡ÛÙËÌ· Î·È Ó· ·Ú¿ÁÔÓÙ·È ·ÓÙÈÛÒÌ·Ù·. ŒÙÛÈ, Á›- ¶ÚÔÔÙÈΤ˜ ÓÂÙ·È ÚÔÛ¿ıÂÈ· Ó· ¯ÔÚËÁËıÔ‡Ó ÔÈ ÚˆÙ½Ó˜ ÙˆÓ ÂÌ‚ÔÏ›ˆÓ ÌÂ Ô˘Û›Â˜ Ô˘ ÌÔÚÔ‡Ó Ó· ÍÂÁÂÏ¿ÛÔ˘Ó √È ÚÔÔÙÈΤ˜ ÙˆÓ ÂÌ‚ÔÏ›ˆÓ Û‹ÌÂÚ· ÛÙÚ¤ÊÔÓÙ·È ·ÊÂ- ÙÔÓ ‚ÏÂÓÓÔÁfiÓÔ ÙÔ˘ °∂™ Î·È Ó· Êı¿ÛÔ˘Ó ÛÙÔ ·ÓÔ- Ófi˜ ÌÂÓ ÛÙÔÓ Û¯Â‰È·ÛÌfi ÙˆÓ Ó¤ˆÓ ÂÌ‚ÔÏ›ˆÓ Î·È ·ÊÂ- ª. ÷Ù˙ËÛÙ˘ÏÈ·ÓÔ‡-™È‰ËÚÔÔ‡ÏÔ˘ 29
Ù¤ÚÔ˘ ÛÙ· Ó¤· ‰›· ÂÊ·ÚÌÔÁÒÓ ÙˆÓ ÂÌ‚ÔÏ›ˆÓ19. ÏÔ˘˜ Ù‡Ô˘˜ ·ÓÙÈηÚÎÈÓÈ΋˜ ıÂڷ›·˜21,22. ™‹ÌÂÚ·, Ì ÙËÓ ·Ó¿Ù˘ÍË Ù˘ ÁÔÓȉȈ̷ÙÈ΋˜ Î·È °È· ÙËÓ ÚÔÛÙ·Û›· ·ÙÔÈÎÒÓ ·ÙfiÌˆÓ ·fi ÙËÓ ÂÎ- Ù˘ ÚˆÙÂÔÌÈ΋˜, Ô˘ Ô‰‹ÁËÛ·Ó ÛÙËÓ ·ÔÎÚ˘ÙÔÁÚ¿- ‰‹ÏˆÛË ÛÔ‚·ÚÒÓ ·ÏÏÂÚÁÈÎÒÓ ·ÓÙȉڿÛÂˆÓ ˘¿Ú¯Ô˘Ó ÊËÛË ÙˆÓ ÁÔÓÈ‰ÈˆÌ¿ÙˆÓ ÙÔ˘ ·ÓıÚÒÔ˘ Î·È ÙˆÓ ÌÈÎÚÔ- Ù· ÂÌ‚fiÏÈ· ·Â˘·ÈÛıËÙÔÔ›ËÛ˘, Ù· ÔÔ›· Û˘Ó¯Ҙ ÔÚÁ·ÓÈÛÌÒÓ, ÌÔÚ› Ó· ·Ú·Û΢·ÛıÔ‡Ó ÂÌ‚fiÏÈ· ÁÈ· ÂÍÂÏ›ÛÛÔÓÙ·È fiÛÔÓ ·ÊÔÚ¿ ÙËÓ ·Ú·Û΢‹ ÙÔ˘˜ Ì ÙȘ ÌÈÎÚÔÔÚÁ·ÓÈÛÌÔ‡˜, Ô˘ Ù· ÙÂÏÂ˘Ù·›· 200 ÂÚ›Ô˘ Ӥ˜ Ù¯ÓÈΤ˜, ¤ÙÛÈ ÒÛÙ ӷ Â›Ó·È ÈÔ ·ÛÊ·Ï‹ ηٿ ÙË ¯ÚfiÓÈ· ıˆÚ›ÙÔ ·‰‡Ó·ÙÔ Ì ÙȘ ÌÂıfi‰Ô˘˜ Ô˘ ¯ÚË- ¯ÔÚ‹ÁËÛ‹ ÙÔ˘˜. ÛÈÌÔÔÈÔ‡ÓÙÔ18-20. ΔÔ ÂÌ‚fiÏÈÔ Ù˘ ˘¤ÚÙ·Û˘ Â›Ó·È ıÂڷ¢ÙÈÎfi ∞ÓÔ›ÁÔÓÙ·È ÏÔÈfiÓ Ó¤Â˜ ÚÔÔÙÈΤ˜ ÁÈ· ÙËÓ ·Ú·- ÂÌ‚fiÏÈÔ Î·È ÂÚȤ¯ÂÈ ˆ˜ ·ÓÙÈÁfiÓÔ ÙÔ CYT006-AngQb. Û΢‹ ÂÌ‚ÔÏ›ˆÓ: ·) ÁÈ· ÌÈÎÚÔÔÚÁ·ÓÈÛÌÔ‡˜ Ô˘ ‰ÂÓ ΔÔ ·ÓÔÛÈ·Îfi Û‡ÛÙËÌ· ·Ú¿ÁÂÈ ·Óٛۈ̷ ¤Ó·ÓÙÈ ÙÔ˘ ÌÔÚԇ̠ӷ ηÏÏÈÂÚÁ‹ÛÔ˘ÌÂ, ‚) ÁÈ· ÌÈÎÚÔÔÚÁ·ÓÈ- ÂÙȉ›Ô˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘ ππ17,24. ÛÌÔ‡˜ Ô˘ ¤¯Ô˘Ó ‰È¿ÊÔÚÔ˘˜ ÔÚÔÙ‡Ô˘˜ Î·È ÔÚÔÔÌ¿- √È ÔÚ›˙ÔÓÙ˜ Ù˘ ÂÓÂÚÁËÙÈ΋˜ ·ÓÔÛÔÔ›ËÛ˘ ‰È·- ‰Â˜ Î·È ‰ÂÓ ¤¯Ô˘Ó ÎÔÈÓ¿ ·ÓÙÈÁfiÓ· Èηӿ Ó· ·Á¿ÁÔ˘Ó ÁÚ¿ÊÔÓÙ·È ·ÓÔÈÎÙÔ› Î·È ÂÏȉÔÊfiÚÔÈ Ì ٷ Ó¤· ÂÌ‚fiÏÈ· ÚÔÛٷ٢ÙÈ΋ ·ÓÔÛÔÏÔÁÈ΋ ·¿ÓÙËÛË, Á) ÁÈ· ÌÈÎÚÔÔÚ- Ô˘ ·Ó·Ù‡ÛÛÔÓÙ·È ÁÈ· ÙËÓ ÚfiÏË„Ë ÙˆÓ ÏÔÈ̈‰ÒÓ Î·È Á·ÓÈÛÌÔ‡˜ Ô˘ ÌÔÚ› Ó· ·Ú¿ÁÔ˘Ó ·˘ÙÔ¿ÓÔÛ· ÓÔÛ‹- ÌË ÏÔÈ̈‰ÒÓ ÓÔÛËÌ¿ÙˆÓ. Ì·Ù· fiˆ˜ Ô ‚′ ·ÈÌÔÏ˘ÙÈÎfi˜ ÛÙÚÂÙfiÎÔÎÎÔ˜ Ù˘ ÔÌ¿- ‰·˜ ∞, ‰) ÁÈ· ÌÈÎÚÔÔÚÁ·ÓÈÛÌÔ‡˜ Ì ‰È·ÊÔÚÂÙÈ΋ ηٷ- μÈ‚ÏÈÔÁÚ·Ê›· ÓÔÌ‹ ÛÙȘ ‰È¿ÊÔÚ˜ Ë›ÚÔ˘˜, Â) ÁÈ· ÌÈÎÚÔÔÚÁ·ÓÈ- ÛÌÔ‡˜ Ì ÌfiÓÔ ÍÂÓÈÛÙ‹ ÙÔÓ ¿ÓıÚˆÔ1,3,17,18. 1. Plotkin SA. Vaccines: past, present and future. Nat Med 2005; 11: s5-11. ∏ ·ÔÎÚ˘ÙÔÁÚ¿ÊËÛË ÙˆÓ ÁÔÓÈ‰ÈˆÌ¿ÙˆÓ ÙÔ˘ ·Ó- 2. Ricciardi W. The old Edward Jenner and the new public ıÚÒÔ˘ Î·È ÌÈÎÚÔÔÚÁ·ÓÈÛÌÒÓ Ô‰‹ÁËÛ ÛÙË Û˘ÁÎÚÈÙÈ΋ health: the future of vaccines in Europe. Eur J Pub Heal ÁÔÓȉȈ̷ÙÈ΋ fiÔ˘ Á›ÓÂÙ·È Û‡ÁÎÚÈÛË Ù˘ ·ÎÔÏÔ˘ı›·˜ 2008; 18(4): 353. ÙˆÓ ÓÔ˘ÎÏÂÔÙȉ›ˆÓ ÙÔ˘ DNA Î·È ·Ê·ÈÚÂ›Ù·È ÙÔ ÙÌ‹Ì· 3. Plotkin SA, Orenstein WA, Offit PA. Vaccines, 2008 Ed: ÙÔ˘ DNA Ô˘ ÚÔηÏ› ÓfiÛÔ17-20. Elsevier-Saunders Braun M. Toward better vaccine safety ™‹ÌÂÚ· ˘¿Ú¯Ô˘Ó ÚÔÔÙÈΤ˜ ÁÈ· Ó· Â›Ó·È Ù· ÂÌ- data and safer vaccination. Pediatrics 2008; 121: 625-6. ‚fiÏÈ· Ì ˙ÒÓÙ˜ ÌÈÎÚÔÔÚÁ·ÓÈÛÌÔ‡˜ ÈÔ ·ÛÊ·Ï‹. ∞˘Ùfi 4. Lowy DR, Schiller JT. Prophylactic human papillomavirus ÂÈÙ˘Á¯¿ÓÂÙ·È Ì ÙȘ Û‡Á¯ÚÔÓ˜ ÌÂıfi‰Ô˘˜ Ù˘ ÌÔÚÈ·- vaccines. J Clin Invest 2006; 116(5): 1167-73. ΋˜ ‚ÈÔÏÔÁ›·˜. √È ÂÚ¢ÓËÙ¤˜ ÏÔÈfiÓ ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ 5. Carstens M. Opportunities and challenges in vaccine deli- very. Eur J Pharm Scien 2009; 36: 605-8. ·˘Ù¤˜ ÙȘ ÌÂıfi‰Ô˘˜ ÂÈÙ˘Á¯¿ÓÔ˘Ó ÙËÓ ·Ê·›ÚÂÛË ÁÔÓÈ- 6. Serruto D, Rappuoli R. Post-genomic vaccine development. ‰È·ÎÒÓ ·ÎÔÏÔ˘ıÈÒÓ (˘Â‡ı˘ÓˆÓ ÁÈ· ÙË Ïԛ̈ÍË ‹ Úfi- FEBS Let 2006; 580: 2985-92. ÎÏËÛË ¿ÏÏˆÓ ÓÔÛËÌ¿ÙˆÓ .¯., ·˘ÙÔ·ÓfiÛˆÓ) ‹ ·ÎfiÌË 7. Ellenberg SS, Foulkes MA, Midthun K, Goldenthal KL. Eva- Î·È ÙËÓ ÙÚÔÔÔ›ËÛË ÙÔ˘ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡ ÙˆÓ ÌÈÎÚÔ- luating the safety of new vaccines: summary of a work- ÔÚÁ·ÓÈÛÌÒÓ, Ì ·ÔÙ¤ÏÂÛÌ· Ù· ÂÌ‚fiÏÈ· ·˘Ù¿ Ó· ·Ú¤- shop. Amer J Public Heal 2005; 95(5): 800-7. ¯Ô˘Ó Ì·ÎÚÔ¯ÚfiÓÈ· ·ÓÔÛ›· ·ÏÏ¿ Ó· Â›Ó·È ÈÔ ·ÛÊ·Ï‹. 8. Dermijian A, Levy O. Safety and efficacy of neonatal vacci- Δ· ÂÌ‚fiÏÈ· Ó¤·˜ ÁÂÓÈ¿˜ Â›Ó·È ÂÌ‚fiÏÈ· DNA (Ï·- nation. Eur J Immunol 2009; 39: 36-46. ÛÌȉȷο), ÁÂÓˆÌÈο ÂÌ‚fiÏÈ· (‚È‚ÏÈÔı‹ÎË ·ıÔÁfiÓÔ˘ 9. Singh R, Singh S, Lillard J. Past, present and future technolo- ÌÈÎÚÔÔÚÁ·ÓÈÛÌÔ‡), ÂÌ‚fiÏÈ· Ì ·ÓÙÈÁfiÓÔ Ô˘ ÚÔηÏ› gies for oral delivery of therapeutic proteins. J Pharm Scien 2008; 97(7): 2497-523. ÙË ‰È¤ÁÂÚÛË ·ÓÔÛÔÔÈËÙÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ Ì ΢ÙÔΛÓ˜, 1,3,10,17 10. Giudice E, Campbell J. Needle-free vaccine delivery. Adv Û˘ÓıÂÙÈο ÂÙ›‰È· Î·È Ù· ÂÌ‚fiÏÈ· ¯ˆÚ›˜ ‚ÂÏfiÓË . Drug Deliv Rev 2006; 58: 68-89. ∂ÎÙfi˜ ·fi ÙȘ ÎÏ·ÛÈΤ˜ ÂÊ·ÚÌÔÁ¤˜ ÙˆÓ ÂÌ‚ÔÏ›ˆÓ 11. Kendall M. Engineering of needle-free physical methods to ÁÈ· ÙËÓ ÚÔÛÙ·Û›· ·fi ÙȘ Û˘Ì‚·ÙÈΤ˜ ÏÔÈÌÒÍÂȘ, Ó¤· target epidermal cells for DNA vaccination. Vaccine ‰›· ÂÊ·ÚÌÔÁÒÓ ¤¯Ô˘Ó ·ÓÔ›ÍÂÈ Î·È ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÓÂ- 2006; 24: 4651-6. ÔÏ·ÛÌ·ÙÈο ÓÔÛ‹Ì·Ù·, ·ÏÏÂÚÁ›Â˜, ·˘ÙÔ¿ÓÔÛ· ÓÔÛ‹- 12. Slutter B, Hagenaars N, Jiskoot W. Rational design of nasal Ì·Ù·, ˘¤ÚÙ·ÛË Î·È Î¿ÓÈÛÌ·21-24. vaccines. J of Drug Targeting 2008; 16(1): 1-17. Δ· Ó¤· ÂÌ‚fiÏÈ· ÁÈ· Ù· ÓÂÔÏ·ÛÌ·ÙÈο ÓÔÛ‹Ì·Ù· 13. Bivas-Benita M, Ottenhoff T, Junginger H, Borchard G. ı· ÂÚȤ¯Ô˘Ó Ó¤· ·ÓÙÈÁfiÓ· Ù· ÔÔ›· ı· Â›Ó·È ÈÔ ·Ô- Pulmonary DNA vaccination: Concepts, possibilities and perspectives. J of Controlled Release 2005; 107: 1-29. ÙÂÏÂÛÌ·ÙÈο ÛÙËÓ ÂÓÂÚÁÔÔ›ËÛË Ù˘ ·ÓÔÛȷ΋˜ ·¿- 14. Swennen B, Van Damme P, Vellinga A, Coppieters Y, De- ÓÙËÛ˘, ı· ˘¿Ú¯ÂÈ Û˘Ó‰˘·ÛÌfi˜ ÔÏÏÒÓ ·ÓÙÈÁfiÓˆÓ ÁÈ· Ûporter AM. Analysis of factors influencing vaccine up- ÙË ıÂڷ›· ÂÓfi˜ Ù‡Ô˘ ηÚΛÓÔ˘ ÁÈ· ÙË ‚¤ÏÙÈÛÙË ·ÓÙÈ- take: perpectives from Belgium. Vaccine 2002; 20: s5-7. ηÚÎÈÓÈ΋ ·ÓÔÛȷ΋ ·¿ÓÙËÛË Î·È ı· Á›ÓÂÈ ÚÔÛ¿ıÂÈ· 15. Pashine A, Valiante N, Ulmer J. Targeting the innate immu- Û˘Ó‰˘·ÛÌÔ‡ ıÂڷ›·˜ ηÚΛÓÔ˘ Ì ÂÌ‚fiÏÈÔ Î·È ¿Ï- ne response with improved vaccine adjuvants. Nat Med 30 ∂Ì‚fiÏÈ·: ¶ÚÔ‚ÏËÌ·ÙÈÛÌÔ› Î·È ÚÔÔÙÈΤ˜
2005;11(4): 563-8. 21. Itoh K, Yamada A, Mine T, Noguchi M. Recent advances in 16. Friede M, Aguado MT. Need for new vaccine formulations cancer vaccines: An overview. Jpn J Clin Oncol 2009; and potential of particulate antigen and DNA delivery 39(2): 73-80. systems. Adv Drug Deliv Rev 2005; 57: 325-31. 22. Emens LA. Chemotherapy and tumor immunity: An unex- 17. Plotkin SA. New vaccination strategies. Bull Acad Natl Med pected collaboration. Front Bioscien 2008; 13: 249-57. 2008; 192(3): 511-8. 23. Moreno A, Janda K. Immunopharmacotherapy: vaccination 18. Makela PH. Vaccines, coming of age after 200 years. FEMS strategies as a treatment for drug abuse and dependen- Microbiol Rev 2000; 24: 9-20. ce. Pharm, Biochem and Behavior 2009; 199-205. 19. ∫·ÏÔÁÂÚ›‰Ë˜ ∞£. °ÂÓˆÌÈ΋: ªÈ· ηıÔÚÈÛÙÈ΋ ÚfiÎÏËÛË 24. Poland GA, Murray D, Bonilla-Guerrero R. New vaccine ÁÈ· ÙÔ Ì¤ÏÏÔÓ Ù˘ ·ÓÔÛÔÏÔÁ›·˜. ∞ÓÔÛ›· 2007; 3(1-2): development. BMJ 2002; 324: 1315-9. 44-64. 20. ∫ˆÓÛÙ·ÓÙÔ˘Ï¿Î˘ ¶. Genomics Î·È proteomics (biomics) ÛÙËÓ È·ÙÚÈ΋ ÙÔ˘ ̤ÏÏÔÓÙÔ˜. ™ÂÌÈÓ¿ÚÈÔ ∞ÓÔÛÔÏÔÁ›·˜ ∞ÏÏËÏÔÁÚ·Ê›·: 2002; 20Ô˜ ·ÎÏÔ˜: 189-171. E-mail: [email protected] ∞˘ÙÔ¿ÓÔÛ· ÓÔÛ‹Ì·Ù·
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2009; 1: 31 – 34
∏ ÂÚÈÁÚ·Ê‹ ÙÔ˘ ·ÓÔÛÈ·ÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ ı· ÌÔ- ÙÔ˘ ·ÓÔÛÈ·ÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ ÛÙË Ïԛ̈ÍË Î·È ÛÙËÓ ÚÔ‡Û ӷ Â›Ó·È ‰·È‰·Ï҉˘ Î·È ‰˘ÛÓfiËÙË, ηıÒ˜ Ë Î·ÚÎÈÓÔÁ¤ÓÂÛË. ∏ ·˘ÙÔ·ÓÔÛ›· fï˜, Ë ÓfiÛÔ˜ ¤Ó·- ÚfiÔ‰Ô˜ Ù˘ ÂÈÛÙ‹Ì˘ ¤¯ÂÈ Û˘Ì‚¿ÏÂÈ ÛÙËÓ ÙÂÎÌË- ÓÙÈ Â·˘ÙÔ‡, ‰È¤ÂÙ·È ·fi ÈÔ ÂÎÏÂÙ˘Ṳ̂ÓË ÏÔÁÈ΋ Ú›ˆÛË ÔÏÏÒÓ Ì˯·ÓÈÛÌÒÓ Ô˘ ‰È¤Ô˘Ó ÙË Ê˘ÛÈÔ- Î·È Ë Î·Ù·ÓfiËÛ‹ Ù˘ ··ÈÙ› ÙË ÛÙ·‰È·Î‹ ÚÔÛ¤ÁÁÈ- ÏÔÁ›· ÙÔ˘. ¶·ÚfiÏ· ·˘Ù¿, Ì ·Ï¿ ÏfiÁÈ·, ÙÔ ·ÓÔÛÈ·- ÛË ÙˆÓ Â·ÁˆÁÈÎÒÓ Ì˯·ÓÈÛÌÒÓ ÙÔ˘ ·ÓÔÛÈ·ÎÔ‡ Û˘- Îfi Û‡ÛÙËÌ· ÂÚÈÁÚ¿ÊÂÙ·È ˆ˜ Ô Î‡ÚÈÔ˜ ÔÌÔÈÔÛÙ·ÙÈ- ÛÙ‹Ì·ÙÔ˜. Îfi˜ Ì˯·ÓÈÛÌfi˜ ÙÔ˘ ·ÓıÚÒÈÓÔ˘ ÔÚÁ·ÓÈÛÌÔ‡. ∂›Ó·È ™Â ÁÂÓÈΤ˜ ÁÚ·Ì̤˜ Ë ·˘ÙÔ·ÓÔÛ›· ‰È·¯ˆÚ›˙Â- ÙÔ Û‡ÛÙËÌ· Ô˘ «·ÈÛı¿ÓÂÙ·È» ÔÔÈ·‰‹ÔÙ ÌÂÙ·- Ù·È ÛÙË Û˘ÛÙËÌ·ÙÈ΋ Î·È ÙËÓ ÔÚÁ·ÓÔÂȉÈ΋. ™ÙËÓ ‚ÔÏ‹ ÛÙÔ ·fiÚ·ÙÔ ÌÈÎÚÔÂÚÈ‚¿ÏÏÔÓ Î·È ˆ˜ «¤ÎÙË ·›- ÚÒÙË, Ë ¤ÎÊÚ·ÛË ·˘ÙÔ·ÓÔÛ›·˜ ÂÚÈÏ·Ì‚¿ÓÂÈ ·- ÛıËÛË» ÎÈÓËÙÔÔÈ› ·˘ÙfiÌ·Ù· ··ÓÙËÙÈÎÔ‡˜ Ì˯·ÓÈ- Ú·¿Óˆ ·fi ¤Ó· Û˘ÛÙ‹Ì·Ù· Ì ¯·Ú·ÎÙËÚÈÛÙÈο ·- ÛÌÔ‡˜. Ú·‰Â›ÁÌ·Ù· ÙË ÚÂ˘Ì·ÙÔÂȉ‹ ·ÚıÚ›Ùȉ· Î·È ÙÔÓÓÓ ∏ ÔÌÔÈfiÛÙ·ÛË Ô˘ ÂÈÙÂÏ› ÙÔ ·ÓÔÛÈ·Îfi Û‡- Û˘ÛÙËÌ·ÙÈÎfi ÂÚ˘ıËÌ·ÙÒ‰Ë Ï‡ÎÔ, ÂÓÒ ÛÙË ‰Â‡ÙÂÚË ÛÙËÌ· ¤¯ÂÈ ÔÏϤ˜ Û˘ÓÈÛٷ̤Ó˜. ∏ ·ÓÙÈÌÂÙÒÈÛË ·ÊÔÚ¿ Û˘ÁÎÂÎÚÈ̤ÓÔ fiÚÁ·ÓÔ-ÛÙfi¯Ô, fiˆ˜ ı˘ÚÂÔ- ÏÔÈÌÒ͈Ó, Ë ÂÈÙ‹ÚËÛË ÙÔ˘ ΢ÙÙ·ÚÈÎÔ‡ ÔÏÏ·- Âȉ‹, ¿ÁÎÚ·˜, ‹·Ú Ì ·Ó¿ÏÔÁ˜ ÎÏÈÓÈΤ˜ ÂΉË- Ï·ÛÈ·ÛÌÔ‡ Î·È Ù˘ ηÚÎÈÓÔÁ¤ÓÂÛ˘ ·ÏÏ¿ Î·È Ë ÎÈ- ÏÒÛÂȘ.1 ÓËÙÔÔ›ËÛË Ì˯·ÓÈÛÌÒÓ Ô˘ ÂÌÔ‰›˙Ô˘Ó ÙËÓ ·Ó¿- Δ· ·ÙÙ·Ú· ÙÔ˘ ·ÓÔÛÈ·ÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ Ô˘ Ù˘ÍË ·˘ÙÔ·ÓÔÛ›·˜ Â›Ó·È ÔÈ Î‡ÚÈÔÈ ˘ÏÒÓ˜ ¤ÎÊ·Ó- ÂÌϤÎÔÓÙ·È ÛÙËÓ ·˘ÙÔ·ÓÔÛ›· Â›Ó·È Ù· Δ ÏÂÌÊÔ·Ù- Û˘ ÙÔ˘ ·ÓÔÛÈ·ÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ ÛÙËÓ Î·ıËÌÂÚÈÓ‹ Ù·Ú·, Ù· μ ÏÂÌÊÔ·ÙÙ·Ú· Î·È Ù· ÌÔÓÔ‡ÚËÓ·-Ì·- Ú·ÎÙÈ΋. ÎÚÔÊ¿Á·. ∏ ÌÂٷ͇ ÙÔ˘˜ ÂÈÎÔÈÓˆÓ›· Â›Ó·È ·˘Ù‹ Ô˘ √È Â·ÁˆÁÈÎÔ› Ì˯·ÓÈÛÌÔ› ÙÔ˘ ·ÓÔÛÈ·ÎÔ‡ Û˘- Ì ÙÔ Û˘ÓÔ‰fi ‰›ÎÙ˘Ô Î˘ÙÙ·ÚÔÎÈÓÒÓ Î·Ù¢ı‡ÓÂÈ ÙËÓ ÛÙ‹Ì·ÙÔ˜ ·Ó Î·È Â›Ó·È Ôχ ‰È·ÊÔÚÂÙÈÎÔ› ÌÂٷ͇ ·ÓÔÛȷ΋ ·fiÎÚÈÛË ÛÙËÓ ·˘ÙÔ·ÓÔÛ›·. Δ· Δ ÏÂÌÊÔ- ÙÔ˘˜, ÂÓÙÔ‡ÙÔȘ ‰ÈÂÎÂÚ·ÈÒÓÔÓÙ·È ·fi ÎÔÈÓ¿ ·ÙÙ·Ú·. ·ÙÙ·Ú· ·Ú¿ÁÔÓÙ·È ·fi ÙÔÓÓ ı‡ÌÔ ·‰¤Ó· ηÈ, Δ· ·ÓÔÛÔ˚ηӿ ·ÙÙ·Ú· Ô˘ ı· ÎÈÓËÙÔÔÈËıÔ‡Ó ÁÈ· ·ÊÔ‡ ÂÚ¿ÛÔ˘Ó ·fi ‰È¿ÊÔÚ· ÛÙ¿‰È· ˆÚ›Ì·ÓÛ˘, ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÌÈ·˜ Ïԛ̈͢ Â›Ó·È Ù· ›‰È· Ô˘ Û ÌÂÙ·Ó·ÛÙÂ‡Ô˘Ó ÛÙÔ˘˜ ÂÚÈÊÂÚÈÎÔ‡˜ ÏÂÌÊ·‰¤Ó˜ ‰È·ÊÔÚÂÙÈÎfi ÂÚÈ‚¿ÏÏÔÓ ÂÌϤÎÔÓÙ·È ÛÙËÓ ÔÚÁ¿Óˆ- fiÔ˘ ˘Ê›ÛÙ·ÓÙ·È, ·ÏÏ¿ Î·È ÎÈÓËÙÔÔÈÔ‡Ó ÂÚ·ÈÙ¤Úˆ ÛË Ì˯·ÓÈÛÌÒÓ ·˘ÙÔ·ÓÔÛ›·˜. ™ÙÔ˘˜ ÎÔÈÓÔ‡˜ ·˘ÙÔ‡˜ ÂÍÂȉ›Î¢ÛË. Δ· μ ÏÂÌÊÔ·ÙÙ·Ú· ·Ú¿ÁÔÓÙ·È ÛÙÔÓ Â·ÁˆÁÈÎÔ‡˜ Ì˯·ÓÈÛÌÔ‡˜ ÙÔ˘ ·ÓÔÛÈ·ÎÔ‡ Û˘ÛÙ‹Ì·- Ì˘ÂÏfi ÙˆÓ ÔÛÙÒÓ Î·È ÌÂÙ·Ó·ÛÙÂ‡Ô˘Ó Î·È ·˘Ù¿ ÙÔ˜ ÔÊ›ÏÂÙ·È ÂÓ Ì¤ÚÂÈ Î·È Ë ¿ÌÂÛË Û˘Û¯¤ÙÈÛË Ïԛ̈- ÛÙÔ˘˜ ÂÚÈÊÂÚÈÎÔ‡˜ ÏÂÌÊ·‰¤Ó˜ fiÔ˘ ˘Ê›ÛÙ·ÓÙ·È Í˘-·˘ÙÔ·ÓÔÛ›·˜-ηÚÎÈÓÔÁ¤ÓÂÛ˘. ÂÚ·ÈÙ¤Úˆ ÂÍÂȉ›Î¢ÛË Ì ÙË ‚Ô‹ıÂÈ· Δ ÏÂÌÊÔ΢Ù- ∂›Ó·È ‡ÎÔÏÔ Ó· ·ÓÙÈÏËÊı› ηÓ›˜ ÙÔÓ ÚfiÏÔ Ù¿ÚˆÓ Î·È ‰ÂÓ‰ÚÈÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ. √È ÂÚÈÊÂÚÈÎÔ› 32 ∂ÈÛ·ÁˆÁ‹ ÛÙËÓ ·˘ÙÔ·ÓÔÛ›·
¶›Ó·Î·˜ 1. ∞ÓÔ¯‹ ÛÙ· Δ Î·È μ ÏÂÌÊÔ·ÙÙ·Ú·
Δ ÏÂÌÊÔ·ÙÙ·Ú· μ ÏÂÌÊÔ·ÙÙ·Ú· ΔÔÔÁÚ·Ê›· £‡ÌÔ˜, ÂÚÈʤÚÂÈ· ª˘ÂÏfi˜ √ÛÙÒÓ, ÂÚÈʤÚÂÈ· ™Ù¿‰ÈÔ øڛ̷ÓÛ˘ CD4+CD8+ ÕˆÚÔ μ ∂ÚÂı›ÛÌ·Ù· ∫ÂÓÙÚÈ΋: À„ËÏ‹ Û˘ÁÁ¤ÓÂÈ· ∫ÂÓÙÚÈ΋: ·Ó·ÁÓÒÚÈÛË ÔÏ˘‰‡Ó·ÌÔ˘ ÁÈ· ·˘ÙÔ·ÓÙÈÁfiÓ· ·ÓÙÈÁfiÓÔ˘ ¶ÂÚÈʤÚÂÈ·: ∞¶∫ ¯ˆÚ›˜ Û˘Ó‰È¤ÁÂÚÛË ¶ÂÚÈʤÚÂÈ·: Δ ·ÓÂÍ¿ÚÙËÙË ·ÓÙÈÁÔÓÔ·Ó·ÁÓÒÚÈÛË ∫‡ÚÈÔÈ ªË¯·ÓÈÛÌÔ› ∞ÓÔ¯‹˜ ∫ÂÓÙÚÈ΋: ·fiÙˆÛË ∫ÂÓÙÚÈ΋: ·fiÙˆÛË, ·Ó·‰È¿Ù·ÍË ˘Ô‰Ô¯¤· ¶ÂÚÈʤÚÂÈ·: ·Ó¤ÚÁÈ· ¶ÂÚÈʤÚÂÈ·: ·Ó¤ÚÁÈ·
ÏÂÌÊ·‰¤Ó˜ ·ÔÙÂÏÔ‡Ó ÏÔÈfiÓ ÎÔÌ‚ÈÎfi ÛËÌÂ›Ô ÁfiÓ· ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È ÛÙ· Δ ÏÂÌÊÔ·ÙÙ·Ú· ·fi Ù· ÛÙËÓ ÂͤÏÈÍË Ù˘ ·ÓÔÛȷ΋˜ ·¿ÓÙËÛ˘ ÛÙËÓ ·˘ÙÔ- ‰ÂÓ‰ÚÈÙÈο ·ÙÙ·Ú· ·Ô˘Û›· Û˘Ó‰ÈÂÁÂÚÙÈÎÒÓ ÌÔÚ›ˆÓ. ·ÓÔÛ›· ηıÒ˜ ·ÔÙÂÏÔ‡Ó ÙÔ ÛËÌÂ›Ô fiÔ˘ ÔÈ Î˘ÙÙ·- ∏ ·Ô˘Û›· Û˘Ó‰ÈÂÁÂÚÙÈÎÒÓ ÌÔÚ›ˆÓ ‰ÂÓ ÂÈÙÚ¤ÂÈ ÙËÓ ÚÈÎÔ› ÏËı˘ÛÌÔ› ˆÚÈÌ¿˙Ô˘Ó Û ÈÔ fi„ÈÌ· ÛÙ¿‰È· ÂÚ·ÈÙ¤Úˆ ·fiÎÚÈÛË ÙˆÓ Δ ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ ÛÙÔ ÂÚ¤- ‰È·ÊÔÚÔÔ›ËÛ‹˜ ÙÔ˘˜1. ıÈÛÌ· Ô˘ ‰¤¯ÔÓÙ·È ·fi Ù· ‰ÂÓ‰ÚÈÙÈο ·ÙÙ·Ú·, η- ıÈÛÙÒÓÙ·˜ Ù· ·ÓÂÓÂÚÁ¿. ∏ ÌË ·fiÎÚÈÛË ÙˆÓ Δ ÏÂÌ- ∞ÓÔÛȷ΋ ∞ÓÔ¯‹ ÊÔ΢ÙÙ¿ÚˆÓ Û ·˘ÙÔ·ÓÙÈÁfiÓ· ÔÓÔÌ¿˙ÂÙ·È ·Ó¤ÚÁÈ· Î·È ·ÔÙÂÏ› ÙÔÓ Â·ÁˆÁÈÎfi Ì˯·ÓÈÛÌfi ÂÚÈÊÂÚÈ΋˜ μ·ÛÈ΋ ¤ÓÓÔÈ· Ù˘ ·˘ÙÔ·ÓÔÛ›·˜ Â›Ó·È Ë ·ÓÔÛȷ΋ ·ÓÔÛȷ΋˜ ·ÓÔ¯‹˜ ÁÈ· Ù· Δ ÏÂÌÊÔ·ÙÙ·Ú·. ·ÓÔ¯‹. ∂›Ó·È Ë ÈηÓfiÙËÙ· ÙÔ˘ ·ÓÔÛÈ·ÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ °È· Ù· μ ÏÂÌÊÔ·ÙÙ·Ú· Ë ‰È·‰Èηۛ· Ù˘ ÎÂ- Ó· ÌËÓ ·ÓÙȉڿ ¤Ó·ÓÙÈ ·ÓÙÈÁfiÓˆÓ ÙÔ˘ ›‰ÈÔ˘ ÙÔ˘ ÔÚ- ÓÙÚÈ΋˜ ·ÓÔ¯‹˜ ÂÍÂÏ›ÛÛÂÙ·È ÛÙÔÓ Ì˘ÂÏfi ÙˆÓ ÔÛÙÒÓ, Á·ÓÈÛÌÔ‡ Î·È ÚÔ·ÙÂÈ ÌÂÙ¿ ·fi ηٿÏÏËÏË Âη›- Ì ÙËÓ Î·Ù·ÛÙÚÔÊ‹ ˘ÂÚ·ÓÙȉڷÛÙÈÎÒÓ ÎÏÒÓˆÓ ‰Â˘ÛË ÙˆÓ ·ÓÔÛÔ˚ηÓÒÓ Î˘ÙÙ¿ÚˆÓ. ¶ÚfiÎÂÈÙ·È ÁÈ· (·ÚÓËÙÈ΋ ÂÈÏÔÁ‹) ·ÏÏ¿ Î·È ÙËÓ ·Ó·‰È¿Ù·ÍË ÙˆÓ ‰È·‰Èηۛ· Ô˘ ÍÂÎÈÓ¿ ·fi ÙÔ ÛËÌÂ›Ô ·Ú·ÁˆÁ‹˜ ÙˆÓ ÂÏ·ÊÚÒÓ Ig Ï ·Ï‡ÛˆÓ, ÂÈÙÚ¤ÔÓÙ·˜ Û ·˘ÙÔ·ÓÙÈ- ·ÓÔÛÔ˚ηÓÒÓ Î˘ÙÙ¿ÚˆÓ Î·È Û˘Ó¯›˙ÂÙ·È ÛÙËÓ ÂÚÈʤ- ‰Ú·ÛÙÈο μ ÏÂÌÊÔ·ÙÙ·Ú· Ó· ·ÔÎÙ‹ÛÔ˘Ó ÌË ·˘ÙÔ- ÚÂÈ·. ¢È·ÎÚ›ÓÂÙ·È ÛÙËÓ ÎÂÓÙÚÈ΋ ·ÓÔ¯‹, Ô˘ ·ÊÔÚ¿ Ù· ·ÓÙȉڷÛÙÈÎfi Ê·ÈÓfiÙ˘Ô. ∏ ÂÚÈÊÂÚÈ΋ ·ÓÔ¯‹ ÂÚÈ- ÚÒÈÌ· ÛÙ¿‰È· ÂͤÏÈ͢ ÙˆÓ Δ Î·È μ ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ Ï·Ì‚¿ÓÂÈ ÈÔ ÒÚÈÌ· ÛÙ¿‰È· ‰È·ÊÔÚÔÔ›ËÛ˘ ÙˆÓ μ Î·È ÙËÓ ÂÚÈÊÂÚÈ΋ ·ÓÔ¯‹ Ô˘ ÂÎÊÚ¿˙ÂÙ·È ·fi ÈÔ ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ, ÂÍÂÏ›ÛÛÂÙ·È ÛÙÔ˘˜ ÂÚÈÊÂÚÈÎÔ‡˜ ÒÚÈ̘ ÌÔÚʤ˜ ÙˆÓ ›‰ÈˆÓ ΢ÙÙ¿ÚˆÓ. ÏÂÌÊ·‰¤Ó˜ Î·È Û˘Ó›ÛÙ·Ù·È ÛÙËÓ Â·ÁˆÁ‹ ·Ó¤ÚÁÈ·˜ Δ· Δ ÏÂÌÊÔ·ÙÙ·Ú· ·Ú¿ÁÔÓÙ·È ·Úı¤Ó· ÛÙÔÓ Â› ·Ó·ÁÓÒÚÈÛ˘ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ·Ô˘Û›· Δ ‚ÔË- ı‡ÌÔ ·‰¤Ó·. ™ÙÔÓ ı‡ÌÔ ˘¿Ú¯ÂÈ ·˘ÍË̤ÓË Û˘ÁΤ- ıËÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ. ™˘ÓÔÙÈο ÔÈ ÂÎÊ¿ÓÛÂȘ ·ÓÔ¯‹˜ ÓÙÚˆÛË ÔÏÏÒÓ ·˘ÙÔ·ÓÙÈÁfiÓˆÓ. ∂Λ, ÔÈ Δ Î˘ÙÙ·ÚÈÎÔ› ÛÙ· Δ Î·È μ ÏÂÌÊÔ·ÙÙ·Ú· ·Ú·Ù›ıÂÓÙ·È ÛÙÔÓ ›Ó·- ÏËı˘ÛÌÔ› Ô˘ ·ÓÙȉÚÔ‡Ó ¤ÓÙÔÓ· Ì ٷ ·˘ÙÔ·ÓÙÈÁfi- η 1. Ó· ηٷÛÙÚ¤ÊÔÓÙ·È, ‰È·‰Èηۛ· Ô˘ ÔÓÔÌ¿˙ÂÙ·È ·Ú- ™ÙËÓ ÂÚ›ÙˆÛË Ô˘ ÔÈ ÂÔÙÈÎÔ› Ì˯·ÓÈÛÌÔ› ÓËÙÈ΋ ÂÈÏÔÁ‹ Î·È Â›Ó·È Ô Î‡ÚÈÔ˜ Ì˯·ÓÈÛÌfi˜ ·Áˆ- ÙÔ˘ ·ÓÔÛÈ·ÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ ηٷÚÚ‡ÛÔ˘Ó Â¿ÁÂÙ·È Á‹˜ ÎÂÓÙÚÈ΋˜ ·ÓÔ¯‹˜. ªÂ ·˘ÙfiÓ ÙÔÓ ÙÚfiÔ ÂͤگÔ- ·˘ÙÔ·ÓÔÛ›·. √È ·Ú¿ÁÔÓÙ˜ Ô˘ ηıÔÚ›˙Ô˘Ó ÙËÓ ÓÙ·È ·fi ÙÔÓ ı‡ÌÔ ·‰¤Ó· Δ ÏÂÌÊÔ·ÙÙ·Ú· Ô˘ ‰ÂÓ Â·ÁˆÁ‹ ·ÏÏ¿ Î·È ÙËÓ ÔÈÔÙÈ΋ ¤ÎÊ·ÓÛË Ù˘ ·˘ÙÔ·- ı· ÎÈÓËÙÔÔÈ‹ÛÔ˘Ó Ì˯·ÓÈÛÌÔ‡˜ ·˘ÙÔ·ÓÔÛ›·˜ ÛÙËÓ ÓÔÛ›·˜ Â›Ó·È ÂÚÈ‚·ÏÏÔÓÙÈÎÔ› Î·È ÁÂÓÂÙÈÎÔ›. ÂÚÈʤÚÂÈ·. ∂ÎÙfi˜ ·fi ÙËÓ Î·Ù·ÛÙÚÔÊ‹ ÙˆÓ ˘ÂÚ·- ÓÙȉڷÛÙÈÎÒÓ ÎÏÒÓˆÓ, ÛÙÔÓ ı‡ÌÔ ·‰¤Ó· ˆÚÈÌ¿˙Ô˘Ó ∞˘ÙÔ·ÓÔÛ›· – ¶ÂÚÈ‚·ÏÏÔÓÙÈÎÔ› ·Ú¿- Ù· Ú˘ıÌÈÛÙÈο Δ ÏÂÌÊÔ·ÙÙ·Ú·, ÌÈ· ÂȉÈ΋ ηÙËÁÔÚ›· ÁÔÓÙ˜ ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ Ô˘ ηٷÛÙ¤ÏÏÔ˘Ó ÙËÓ ·˘ÙÔ¿ÓÔÛË ‰Ú·ÛÙËÚÈfiÙËÙ· ÛÙËÓ ÂÚÈʤÚÂÈ·2. Œ¯ÂÈ ·Ú·ÙËÚËı› ˆ˜ Ë ·˘ÙÔ·ÓÔÛ›· Û¯ÂÙ›˙ÂÙ·È ‹ Î·È Œ¯ÂÈ ·Ú·ÙËÚËı› fï˜ ·ÓÔÛȷ΋ ·ÓÔ¯‹ Î·È ÂÈ‚·Ú‡ÓÂÙ·È Ì ÙȘ ÏÔÈÌÒÍÂȘ. ∞ӷʤÚıËΠ·Ú·¿- ¤Ó·ÓÙÈ ·˘ÙÔ·ÓÙÈÁfiÓˆÓ Ô˘ ‰ÂÓ ‚Ú›ÛÎÔÓÙ·È ÛÙÔÓ ı‡ÌÔ Óˆ ˆ˜ Ë ÎÈÓËÙÔÔ›ËÛË ·ÚfiÌÔÈˆÓ Î˘ÙÙ·ÚÈÎÒÓ ÏË- ·‰¤Ó·. ∏ ·ÓÔ¯‹ ¤Ó·ÓÙÈ ·˘ÙÒÓ ÙˆÓ ·˘ÙÔ·ÓÙÈÁfiÓˆÓ ı˘ÛÌÒÓ ÛÙË Ïԛ̈ÍË Î·È ÛÙËÓ ·˘ÙÔ·ÓÔÛ›· ¤¯ÂÈ ˆ˜ ¿ÁÂÙ·È ÛÙËÓ ÂÚÈʤÚÂÈ· (ÂÚÈÊÂÚÈ΋ ·ÓÔ¯‹) Î·È ·ÔÙ¤ÏÂÛÌ· ÙËÓ ¿ÌÂÛË ÂÌÏÔ΋ ÌÂٷ͇ ÙÔ˘˜. ∏ ÏÔ›- ·ÊÔÚ¿ ÏËı˘ÛÌÔ‡˜ ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ Ô˘ ¤¯Ô˘Ó ̈ÍË ÂÌϤÎÂÙ·È ÛÙËÓ Â·ÁˆÁ‹ ·˘ÙÔ·ÓÔÛ›·˜ Ì 2 ÂÁηٷÏ›„ÂÈ ÙÔÓ ı‡ÌÔ ·‰¤Ó· Î·È ¤¯Ô˘Ó ÌÂÙ·Ó·ÛÙ‡- ΢ڛˆ˜ Ì˯·ÓÈÛÌÔ‡˜. ÛÂÈ ÛÙÔ˘˜ ÂÚÈÊÂÚÈÎÔ‡˜ ÏÂÌÊ·‰¤Ó˜. ∂Λ, ·˘ÙÔ·ÓÙÈ- ªÂÙ¿ ÙËÓ ÂÈÛ‚ÔÏ‹ ÏÔÈÌÔÁfiÓÔ˘ ·Ú¿ÁÔÓÙ·, ÂÎ- ∞. ™·Ú·ÓÙfiÔ˘ÏÔ˜ 33
·È‰Â‡ÔÓÙ·È ÂȉÈÎÔ› ΢ÙÙ·ÚÈÎÔ› ÏËı˘ÛÌÔ› Ô˘ ÛÙÚ¤- ¶›Ó·Î·˜ 2. ∫ÚÈÙ‹ÚÈ· Witebsky Î·È Rose ÁÈ· ·˘ÙÔ·ÓÔÛ›· ÊÔÓÙ·È ¤Ó·ÓÙÈ ÂȉÈÎÒÓ ·ÓÙÈÁfiÓˆÓ. ŸÙ·Ó ÔÈ ÂȉÈÎÔ› ·˘- 1Ô ÎÚÈÙ‹ÚÈÔ ∞Ó‡ÚÂÛË ·˘ÙÔ·ÓÙÈÁfiÓˆÓ ÙÔ› ÏËı˘ÛÌÔ› ÂÓÙÔ›ÛÔ˘Ó Î¿ÔÈÔ ·˘ÙÔ·ÓÙÈÁfiÓÔ Ô˘ 2Ô ÎÚÈÙ‹ÚÈÔ ∞Ó‡ÚÂÛË ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ÌÔÈ¿˙ÂÈ Ì ÙÔ ·ÓÙÈÁfiÓÔ Ô˘ ÎÈÓËÙÔÔ›ËÛ ÙË Ïԛ̈ÍË, 3Ô ÎÚÈÙ‹ÚÈÔ ∂ÓÂÚÁfi˜ ·ÓÔÛÔÔ›ËÛË ÙfiÙ ٷ ·ÙÙ·Ú· ÛÙÚ¤ÊÔÓÙ·È ¤Ó·ÓÙÈ ÙÔ˘ ·˘ÙÔ·ÓÙÈÁfi- 4Ô ÎÚÈÙ‹ÚÈÔ ¶·ıËÙÈ΋ ÌÂÙ·ÊÔÚ¿ ÓfiÛÔ˘ ÓÔ˘ ¿ÁÔÓÙ·˜ ·˘ÙÔ·ÓÔÛ›·. √ Ì˯·ÓÈÛÌfi˜ ·˘Ùfi˜ ÔÓÔÌ¿˙ÂÙ·È ÌÔÚȷ΋ ÌÈÌÈ΋ Î·È Â˘ı‡ÓÂÙ·È ÁÈ· ÙË ‰È·- Û˘Ó‰¤ÔÓÙ·È Ì ·˘ÙÔ¿ÓÔÛ· ÓÔÛ‹Ì·Ù·. Ù·Ú·¯‹ ÛÙËÓ ÔÌÔÈfiÛÙ·ÛË ÙÔ˘ ·ÓÔÛÈ·ÎÔ‡ Û˘ÛÙ‹Ì·- ∏ ·Ó·Î¿Ï˘„Ë ·˘ÙÒÓ ÙˆÓ Û˘Ó‰˘·ÛÌ¤ÓˆÓ ÔÏ˘- ÙÔ˜.3 ÌÔÚÊÈÛÌÒÓ Á¤ÓÓËÛ ÙËÓ ·Ó¿ÁÎË Ó· ‚ÚÂı› Ò˜ ·˘Ù¤˜ ∂ÎÙfi˜ ·fi ÙËÓ Â·ÁˆÁ‹ ÂȉÈÎÒÓ ·˘ÙÔ·ÓÙȉڷ- ÔÈ ÁÂÓÂÙÈΤ˜ ı¤ÛÂȘ ÂÌϤÎÔÓÙ·È ÛÙËÓ ·ıÔÊ˘ÛÈÔÏÔ- ÛÙÈÎÒÓ ÏËı˘ÛÌÒÓ, Ë ›‰È· Ë Ïԛ̈ÍË ÎÈÓËÙÔÔÈ› ÙËÓ Á›· Ù˘ ·˘ÙÔ·ÓÔÛ›·˜. ™Â ÁÂÓÈΤ˜ ÁÚ·Ì̤˜, ηٷ‰Â›- ¤ÎÊÚ·ÛË Û˘Ó‰ÈÂÁÂÚÙÈÎÒÓ ÌÔÚ›ˆÓ ·fi Ù· ·ÓÙÈÁÔÓÔ- ¯ıËΠˆ˜ Ù· ÁÔÓȉȷο ·Ú¿ÁˆÁ· ÂËÚ¿˙Ô˘Ó 1. ÙÔ ·ÚÔ˘ÛÈ·ÛÙÈο ·ÙÙ·Ú·. Δ· ·ÙÙ·Ú· ϤÔÓ Î·ı›ÛÙ·- Â›Â‰Ô ·ÓÔ¯‹˜ (fiˆ˜ ·˘Ù‹ ÂÚÈÁÚ¿ÊËΠ·Ú·¿- ÓÙ·È Èηӿ Ó· Âηȉ‡ÛÔ˘Ó ·ÓÔÛÔ˚ηӿ Δ ÏÂÌÊÔ- Óˆ), 2. ÙËÓ ·ÚÓËÙÈ΋ ÂÈÏÔÁ‹ ·˘ÙÔ·ÓÙȉڷÛÙÈÎÒÓ Δ Î‡ÙÙ·Ú· ηٷÚÁÒÓÙ·˜ ÙËÓ Â·ÁˆÁ‹ ·Ó¤ÚÁÈ·˜ Ô˘ ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ, ›Ù 3. ÙËÓ ·Ó¤ÚÁÈ· Û ·˘ÙÔ·ÓÙÈÁfiÓ·. ·Ó·Ê¤ÚıËΠ·Ú·¿Óˆ Î·È Ô˘ ·ÔÙÂÏ› ÙÔÓ Î‡ÚÈÔ Ã·Ú·ÎÙËÚÈÛÙÈÎfi ·Ú¿‰ÂÈÁÌ· Â›Ó·È ÔÈ ÔÏ˘ÌÔÚ- Ì˯·ÓÈÛÌfi ÂÚÈÊÂÚÈ΋˜ ·ÓÔ¯‹˜ (¶›Ó. 1). ∏ ηٿÚ- ÊÈÛÌÔ› ÙÔ˘ MHCII. ¶ÂÈÚ¿Ì·Ù· Û Knock out ÔÓÙ›ÎÈ· ÁËÛË Ù˘ ÂÚÈÊÂÚÈ΋˜ ·ÓÔ¯‹˜ ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ¤‰ÂÈÍ·Ó fiÙÈ ÔÈ ÔÏ˘ÌÔÚÊÈÛÌÔ› ·˘ÙÔ›: 1. ÂËÚ¿˙Ô˘Ó ÂÎÙfi˜ ·fi ÙË ‰ËÌÈÔ˘ÚÁ›· ·˘ÙÔ·ÓÙȉڷÛÙÈÎÒÓ Δ ÏÂÌ- ÙËÓ ·ÓÔÛȷ΋ ·ÓÔ¯‹, ‰È·Ù·Ú¿ÛÛÔÓÙ·˜ ÙË ‰È·‰Èηۛ· ÊÔ΢ÙÙ¿ÚˆÓ, ÙË ‰È·ÛÔÚ¿ ÂÈÙfiˆÓ, Ì˯·ÓÈÛÙÈ΋ ·Ó·ÁÓÒÚÈÛ˘ ·˘ÙÔ·ÓÙÈۈ̿وÓ, 2. ÚÔηÏÔ‡Ó ‰È·Ù·- Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ Â·ÁˆÁ‹ ¯ÚÔÓÈfiÙËÙ·˜ ÛÙ· ·˘- Ú·¯‹ ÛÙËÓ ·Ó·ÁÓÒÚÈÛË ·ÓÙÈÁÔÓÈÎÒÓ ÂÈÙfiˆÓ, Ô‰Ë- ÙÔ¿ÓÔÛ· ÓÔÛ‹Ì·Ù·.4 ÁÒÓÙ·˜ ÎψÓÔÙ˘È΋ ¤ÎÙ˘ÍË, ÂÓÒ 3. ÂÌϤÎÔÓÙ·È √ ÙÚ›ÙÔ˜ Û˘Ó‰ÂÙÈÎfi˜ ÎÚ›ÎÔ˜ Ïԛ̈͢-·˘ÙÔ·ÓÔ- ÛÙËÓ ÔÌÔÈfiÛÙ·ÛË ÙˆÓ Ú˘ıÌÈÛÙÈÎÒÓ Δ ÏÂÌÊÔ΢ÙÙ¿- Û›·˜ ·ÊÔÚ¿ ÛÙËÓ ¿ÌÂÛË Î˘ÙÙ·ÚÔÙÔÍÈ΋ ‰Ú¿ÛË Ô˘ ·- ÚˆÓ, ÂȉÈ΋ ÔÌ¿‰· ΢ÙÙ·ÚÈÎÔ‡ ÏËı˘ÛÌÔ‡ Ô˘ Û˘Ì- ÛÎÔ‡Ó ÔÈ ÊÏÂÁÌÔÓÒ‰ÂȘ Ì˯·ÓÈÛÌÔ› Ù˘ Ïԛ̈͢ ÌÂÙ¤¯ÂÈ ÂÓÂÚÁ¿ ÛÙÔ˘˜ ÔÌÔÈÔÛÙ·ÙÈÎÔ‡˜ Ì˯·ÓÈÛÌÔ‡˜ ÛÙÔ˘˜ ÂÚÈÊÂÚÈÎÔ‡˜ ÈÛÙÔ‡˜. ∞Ê’ ÂÓfi˜ ÚÔηÏÂ›Ù·È ¿- Ú‡ıÌÈÛ˘ Ù˘ ·˘ÙÔ¿ÓÔÛ˘ ·fiÎÚÈÛ˘. ÌÂÛË ÈÛÙÈ΋ ‚Ï¿‚Ë, ·Ê’ ÂÙ¤ÚÔ˘, ÏfiÁˆ ÌÂÙÔ˘Û›ˆÛ˘ ™ÙȘ ̤Ú˜ Ì·˜ ÙÔ Î¤ÓÙÚÔ ‚¿ÚÔ˘˜ Ù˘ ÁÂÓÂÙÈ΋˜ ÚˆÙÂ˚ÓÒÓ, ·Ú¿ÁÔÓÙ·È Î·È ÂÎχÔÓÙ·È ÓÂÔ-›ÙÔÔÈ Î·È ·Ó¿Ï˘Û˘ ¤¯ÂÈ ÂÛÙÈ·Ûı› ÛÙËÓ ·Ó·˙‹ÙËÛË Ù¤ÙÔÈˆÓ ÁÂ- Ó¤Ô-·ÓÙÈÁfiÓ· Èηӿ Ó· ÎÈÓËÙÔÔÈ‹ÛÔ˘Ó ·˘ÙÔ·ÓÔÛ›·. ÓÂÙÈÎÒÓ ÚÔÊ›Ï. ¶·ÚfiÏ· ·˘Ù¿ Ô Î·ıÔÚÈÛÌfi˜ Ù˘ ÁÔ- Óȉȷ΋˜ ‰È·Ù·Ú·¯‹˜ Ô˘ ÂÎÊÚ¿˙ÂÙ·È ·fi Ù· SNPs ∞˘ÙÔ·ÓÔÛ›· – °ÂÓÂÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ Î·È Ë ÂΉ‹ÏˆÛ‹ Ù˘ Û ÎÏÈÓÈÎfi ›‰Ô, ·Ú·Ì¤ÓÂÈ ∞fi ÙȘ ÚÒÙ˜ ·Ú·ÙËÚ‹ÛÂȘ ÛÙ· ·˘ÙÔ¿ÓÔÛ· ÓÔ- ·‰È¢ÎÚ›ÓÈÛÙË. Û‹Ì·Ù· ‹Ù·Ó Ë ÂÓ‰Ô-ÔÈÎÔÁÂÓÂȷ΋ ÙÔ˘˜ ›وÛË. ™˘ÓÔÙÈο, Ù· ÛËÌ›·-ÎÏÂȉȿ ÛÙËÓ ·Ó¿Ù˘ÍË ∂›Ó·È ÁÓˆÛÙfi ˆ˜ Ë ÂÌÊ¿ÓÈÛË Ó·ÓÈÎÔ‡ ‰È·‚‹ÙË Û ·˘ÙÔ·ÓÔÛ›·˜ Â›Ó·È ÔÈ Ì˯·ÓÈÛÌÔ› ·Ó·ÁÓÒÚÈÛ˘ ·˘- ÌÔÓÔ˙˘ÁÒÙË ‰›‰˘ÌÔ Û˘Óԉ‡ÂÙ·È ·fi Èı·ÓfiÙËÙ· ÙÔ·ÓÙÈÁfiÓˆÓ, Ë ÔÌÔÈfiÛÙ·ÛË Ù˘ ΢ÙÙ·ÚÈ΋˜ ·fiÎÚÈ- 35-50% ÂÌÊ¿ÓÈÛ˘ Î·È ÛÙÔÓ ‰Â‡ÙÂÚÔ ÌÔÓÔ˙˘ÁÒÙË. Û˘ ÛÙ· ·˘ÙÔ·ÓÙÈÁfiÓ· (Δ/μ ·ÙÙ·Ú·) Î·È Ë ÈÛÙÈ΋ ∏ Èı·ÓfiÙËÙ· ·˘Ù‹ ÛÙ·ıÌ›˙ÂÙ·È ÛÙÔ 5-6% fiÙ·Ó ÔÈ ‚Ï¿‚Ë. ‰›‰˘ÌÔÈ Â›Ó·È ‰È˙˘ÁÒÙ˜. ∞Ó¿ÏÔÁ˜ ·Ú·ÙËÚ‹ÛÂȘ ¢ÂÓ Ú¤ÂÈ Ó· Û˘Á¯¤ÂÙ·È Ë ÈÛÙÈ΋ ‚Ï¿‚Ë Ì ÙËÓ Ô‰‹ÁËÛ·Ó ÛÙËÓ ˘Ô„›· ˆ˜ ÙÔ ÁÂÓÂÙÈÎfi ÚÔÊ›Ï ·˘ÙÔ·ÓÔÛ›·. πÛÙÈ΋ ‚Ï¿‚Ë ··ÓÙ¿Ù·È Î·ıËÌÂÚÈÓ¿ Û ۯÂÙ›˙ÂÙ·È Ì ÙËÓ ·Ó¿Ù˘ÍË ·˘ÙÔ·ÓÔÛ›·˜. ∏ ÙÂÎÌË- fiÏÔ˘˜ ÙÔ˘˜ ÔÚÁ·ÓÈÛÌÔ‡˜ Î·È ·ÔÙÂÏ› ÌÈ· ÌfiÓÔ Ú›ˆÛË Ù˘ ·Ú·¿Óˆ ·Ú·Ù‹ÚËÛ˘ ÂÈÙ‡¯ıËΠ·fi ÙȘ Û˘ÓÈÛÙÒÛ˜ Ù˘ ·˘ÙÔ·ÓÔÛ›·˜. ∂Í¿ÏÏÔ˘ Ë ÛÙËÓ ÂÔ¯‹ Ù˘ ÁÂÓÂÙÈ΋˜ ·Ó¿Ï˘Û˘, fiÔ˘ Ù˘ÔÔÈ- ·˘ÙÔ·ÓÔÛ›· ηıÔÚ›˙ÂÙ·È ·fi ÙËÓ ÂȂ‚·›ˆÛË 4 ‹ıËÎ·Ó ÁÔÓȉȷΤ˜ ı¤ÛÂȘ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È ÙfiÛÔ Ì ÎÚÈÙËÚ›ˆÓ fiˆ˜ ·˘Ù¿ ıÂÛ›ÛÙËÎ·Ó ·fi ÙÔ˘˜ Witeb- ÙËÓ ·Ó¿Ù˘ÍË fiÛÔ Î·È Ì ÙË ‚·Ú‡ÙËÙ· ¤ÎÊ·ÓÛ˘ ·˘- sky Î·È Rose (¶›Ó. 2)5. Δ· ÎÚÈÙ‹ÚÈ· ·˘Ù¿ ÂÊ·ÚÌfi˙Ô- ÙÔ·ÓÔÛ›·˜. ÓÙ·È ·ÎfiÌË Î·È Û‹ÌÂÚ· Û ÔÏÏ¿ ÓÔÛ‹Ì·Ù· ·ÓÔÛÔ- ™ÙȘ ̤Ú˜ Ì·˜, Ë ÔχÏÔÎË ÁÔÓȉȷ΋ ÚÔÛ¤Á- ÏÔÁÈ΋˜ ·Ú¯‹˜ fiˆ˜ Ë ·ıËÚÔÛÎÏ‹ÚˆÛË, Ë ˘¤ÚÙ·- ÁÈÛË ÙˆÓ ·˘ÙÔ¿ÓÔÛˆÓ ÓÔÛËÌ¿ÙˆÓ Ì ÌÂıfi‰Ô˘˜ ÔÏÈ- ÛË Î.¿. ∏ ¤Ú¢ӷ ÛÙËÓ ÂÔ¯‹ Ì·˜ ÚÔ¯ˆÚ¿ÂÈ Î·È Î‹˜ Î·È ÔÏ˘‰È¿ÛÙ·Ù˘ ÁÂÓˆÌÈ΋˜ ·Ó¿Ï˘Û˘ ¤¯ÂÈ ÂÛÙÈ¿˙ÂÙ·È Ï¤ÔÓ, ÂÎÙfi˜ ·fi ÙËÓ Î·Ù·ÁÚ·Ê‹ ÁÂÓÂÙÈ- Ô‰ËÁ‹ÛÂÈ ÙÔÓ Î·ıÔÚÈÛÌfi Û˘Ó‰˘·ÛÌÔ‡ ϤÔÓ ÁÂÓÂÙÈ- ÎÒÓ ÔÏ˘ÌÔÚÊÈÛÌÒÓ, ÛÙËÓ ÚˆÙÂÔÌÈ΋ ·˘ÙÒÓ ÙˆÓ ÎÒÓ ÌÔÓÔÁÔÓȉȷÎÒÓ ÔÏ˘ÌÔÚÊÈÛÌÒÓ (SNPs) Ô˘ ÁÂÓÂÙÈÎÒÓ ÚÔÊ›Ï. 34 ∂ÈÛ·ÁˆÁ‹ ÛÙËÓ ·˘ÙÔ·ÓÔÛ›·
μÈ‚ÏÈÔÁÚ·Ê›· 4. Ely LK, Burrows SR, Purcell AW, Rossjohn J, McCluskey J. T-cells behaving badly: structural insights into alloreactivity and 1. Lewis ED, Harriman GR, Blutt SE. Organization of the im- autoimmunity. Curr Opin Immunol. 2008; 20(5): 575-80. mune system, in Rich RR, Clinical Immunology. Principles 5. Rose NR, Bona C. Defining criteria for autoimmune diseases and Practise. 3rd Edition, Mosby-Elsevier 2008; 17-38. (Witebsky’s postulates revisited). Immunol Today. 1993; 2. Immunologic Tolerance, in Abbas AK, Lichtman AH, Cel- 14(9): 426-30. lular and Molecular Immunology. 5th Edition, Saunders 2003; 216-39. 3. Mackay IR, Leskovsek NV, Rose NR. Cell damage and au-toimmunity: ∞ÏÏËÏÔÁÚ·Ê›·: a critical appraisal. J Autoimmun. 2008; 30(1-2): 5-11. E-mail: [email protected] ∞˘ÙÔ¿ÓÔÛ· ÓÔÛ‹Ì·Ù·
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TÌ‹Ì· ∫ÏÈÓÈ΋˜ ∞ÓÔÛÔÏÔÁ›·˜, μ′ ¶·ıÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ∞¶£, £ÂÛÛ·ÏÔÓ›ÎË
2009; 1: 35 – 37
™ÎÔfi˜ Ù˘ ·ÚÔ‡Û·˜ ÌÂϤÙ˘ Â›Ó·È Ë Û˘ÓÔÙÈ΋ Â- ÙÔ Û‡ÓÔÏÔ ÙˆÓ ·ÓÔÛÔ˚ηÓÒÓ Î˘ÙÙ¿ÚˆÓ, Ù· ÔÔ›· ·Ï- ÚÈÁÚ·Ê‹ ÙˆÓ ÓÂfiÙÂÚˆÓ ‰Â‰ÔÌ¤ÓˆÓ ÛÙË ‚¿ÛË Ù˘ ·- ÏËÏÂȉÚÔ‡Ó ÌÂٷ͇ ÙÔ˘˜ ̤ۈ ÏËıÒÚ·˜ ΢ÙÙ·ÚÔ- ıÔÊ˘ÛÈÔÏÔÁ›·˜ ÙˆÓ ÓfiÛˆÓ ·˘ÙÒÓ, ηıÒ˜ Î·È Ë Î·Ù¿- ÎÈÓÒÓ Î·È ¯ËÌÂÈÔÎÈÓÒÓ1. ∏ Û˘ÛÛÒÚ¢ÛË ÙˆÓ Î˘ÙÙ¿- ‰ÂÈÍË ÛÙÔ¯Â˘Ì¤ÓˆÓ ıÂڷ¢ÙÈÎÒÓ ·ÚÂÌ‚¿ÛÂˆÓ Ì¤- ÚˆÓ ·˘ÙÒÓ ÛÙÔÓ Ê˘ÛÈÔÏÔÁÈο ÔÏÈÁÔ΢ÙÙ·ÚÈÎfi ·ÚıÚÈ- Ûˆ Ù˘ Û‡Á¯ÚÔÓ˘ ·ÓÔÛÔÏÔÁÈ΋˜ ¤Ú¢ӷ˜. Îfi ˘Ì¤Ó·, ı· Ô‰ËÁ‹ÛÂÈ ÛÙË ‰ËÌÈÔ˘ÚÁ›· ÙÔ˘ ¿ÓÓÔ˘ ηÈ, ÙÂÏÈο, Ù˘ ÔÛÙÈ΋˜ ‰È¿‚ÚˆÛ˘. ƒÂ˘Ì·ÙÔÂȉ‹˜ ∞ÚıÚ›Ùȉ· (ƒ∞) Δ· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ÂÚÈÁÚ¿ÊËÎÂ Ô ÚfiÏÔ˜ ˘Ô- ÔÌ¿‰ˆÓ ÙˆÓ Δ ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ, ȉ›ˆ˜ ÙˆÓ Th17, ÛÙËÓ ∏ ƒ∞ Â›Ó·È ÌÈ· ·˘ÙÔ¿ÓÔÛË ÔÏ˘Û˘ÛÙËÌ·ÙÈ΋ ÓfiÛÔ˜, ·ıÔÊ˘ÛÈÔÏÔÁ›· Ù˘ ƒ∞. Δ· Δh17 ·ÙÙ·Ú· ÂÓÂÚÁÔ- ¿ÁÓˆÛÙ˘ ·ÈÙÈÔÏÔÁ›·˜, Ë ÔÔ›· ÚÔÛ‚¿ÏÏÂÈ ÂÚ›Ô˘ ÔÈÔ‡Ó ¿ÌÂÛ· Ì·ÎÚÔÊ¿Á·, ÈÓÔ‚Ï¿ÛÙ˜ Î·È ÂÓ‰ÔıËÏÈ·- ÙÔ 1% ÙÔ˘ ÁÂÓÈÎÔ‡ ÏËı˘ÛÌÔ‡. ÷ڷÎÙËÚ›˙ÂÙ·È ·fi ο ·ÙÙ·Ú· Î·È Ô‰ËÁÔ‡Ó Û ÏÂÈÙÔ˘ÚÁÈ΋ ˆÚ›Ì·ÓÛË ÙˆÓ Û˘ÌÌÂÙÚÈ΋ ˘ÌÂÓ›Ùȉ·, ·ÏÏ¿ Î·È ‰È·‚ÚˆÙÈΤ˜ ‚Ï¿‚˜ ÙˆÓ ·ÚıÚÒÛˆÓ, Ì ·ÔÙ¤ÏÂÛÌ· ÌfiÓÈ̘ ·Ú·ÌÔÚ- μ ΢ÙÙ¿ÚˆÓ. ∂ÈÚfiÛıÂÙ·, Ù· Δh17 ·ÙÙ·Ú·, ̤ۈ ΢Ù- ÊÒÛÂȘ, ȉ›ˆ˜ ÙˆÓ ¿ÎÚˆÓ ¯ÂÈÚÒÓ Î·È Ô‰ÒÓ. ∏ ‰È¿- Ù·ÚÔÎÈÓÒÓ, ÂÓÂÚÁÔÔÈÔ‡Ó Ù· ¯ÔÓ‰ÚÔ·ÙÙ·Ú· Î·È ÙÔ˘˜ ÁÓˆÛË Ù˘ ÓfiÛÔ˘ ÛÙËÚ›˙ÂÙ·È ÛÙ· ÎÚÈÙ‹ÚÈ· ÙÔ˘ ∞ÌÂ- Û˘ÓÔ‚È·ÎÔ‡˜ ÈÓÔ‚Ï¿ÛÙ˜, Ô‰ËÁÒÓÙ·˜ ÛÙË ‰È¿‚ÚˆÛË, 2 ÚÈηÓÈÎÔ‡ ∫ÔÏÂÁ›Ô˘ ƒÂ˘Ì·ÙÔÏÔÁ›·˜ (1987). ̤ۈ ADAMTS Î·È MMPs, ÙÔ˘ ·ÚıÚÈÎÔ‡ ¯fiÓ‰ÚÔ˘ . ™ÙËÓ ·ıÔÁ¤ÓÂÈ· Ù˘ ƒ∞ ÂÌϤÎÔÓÙ·È Î·Ù¿ ‚¿ÛË ¶·Ú¿ÏÏËÏ·, ̤ۈ ¤ÎÎÚÈÛ˘ ΢ÙÙ·ÚÔÎÈÓÒÓ, fiˆ˜ IL-17, ÁÂÓÂÙÈÎÔ› (HLA-DR4, PTPN22, PAD14, CTLA-4 Î.¿.) TNF, IL-1, RANKL, GM-CSF Î.¿., ηÙ¢ı‡ÓÔ˘Ó ÙË ‰È·- Î·È ÂÚÈ‚·ÏÏÔÓÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ (΢ڛˆ˜ ÙÔ Î¿ÓÈÛÌ· ÊÔÚÔÔ›ËÛË Î·È ÏÂÈÙÔ˘ÚÁÈ΋ ˆÚ›Ì·ÓÛË ÙˆÓ ÔÛÙÂÔÎÏ·- Î·È ‰È¿ÊÔÚÔÈ ÌÈÎÚÔ-ÔÚÁ·ÓÈÛÌÔ›). ∏ ·ÏÏËÏ›‰Ú·ÛË ÛÙÒÓ Ì ÙÂÏÈÎfi ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÔÛÙÈ΋ ‰È¿‚ÚˆÛË2. ΔÂ- ÙˆÓ ·Ú·ÁfiÓÙˆÓ ·˘ÙÒÓ Ô‰ËÁ› ÛÙËÓ ˘ÚÔ‰fiÙËÛË ·˘- ÏÂ˘Ù·›·, ıˆÚÂ›Ù·È fiÙÈ Î·È ÔÈÔÙÈΤ˜ ‹/Î·È ÔÛÔÙÈΤ˜ ÙÔ¿ÓÔÛ˘ ÊÏÂÁÌÔÓ‹˜ (·˘ÙÔ·ÓÔÛ›· ¤Ó·ÓÙÈ ÎÈÙÚÔ˘ÏÏÈ- ‰È·Ù·Ú·¯¤˜ ÙˆÓ Δ Ú˘ıÌÈÛÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ Û˘Ì‚¿Ï- ÓÔÔÈËÌ¤ÓˆÓ Î˘ÎÏÈÎÒÓ ÂÙȉ›ˆÓ, IgG, ÁÏ˘ÎÔÚˆ- ÏÔ˘Ó ÛÙËÓ ·ıÔÁ¤ÓÂÛË Ù˘ ·ÚıÚÈ΋˜ ‚Ï¿‚˘. Ù½Ó˘ 39, ÛÙÔȯ›ˆÓ ÙÔ˘ ÎÔÏÏ·ÁfiÓÔ˘ Î.¿.), Ë ÔÔ›·, √ ÚfiÏÔ˜ ÙˆÓ μ ΢ÙÙ¿ÚˆÓ ¤ÁÎÂÈÙ·È, ΢ڛˆ˜, ÛÙËÓ ÌÂÙ¿ ·fi ¿ÏÏÔÙ ¿ÏÏÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ·, ÚÔηÏ› ÈηÓfiÙËÙ· ÂÂÍÂÚÁ·Û›·˜ Î·È ·ÚÔ˘Û›·Û˘ ·ÓÙÈÁfiÓÔ˘, ÊÏÂÁÌÔÓÒ‰Ë ‚Ï¿‚Ë ÙˆÓ ·ÚıÚÒÛˆÓ1. ™ÙËÓ fiÏË ‰ÈÂÚ- ÛÙËÓ ·Ú·ÁˆÁ‹ ·ÓÙÈÛˆÌ¿ÙˆÓ (ÚÂ˘Ì·ÙÔÂȉ›˜ ·Ú¿- Á·Û›· ÂÓÙfi˜ ÙÔ˘ ·ÚıÚÈÎÔ‡ ˘Ì¤Ó·, Û˘ÌÌÂÙ¤¯ÂÈ Û¯Â‰fiÓ ÁÔÓÙ˜, ·nti-CCPs, anti-GP39) ηıÒ˜ Î·È ÛÙËÓ ¤ÎÎÚÈ- 36 ™˘ÛÙËÌ·ÙÈο ·˘ÙÔ¿ÓÔÛ· ÓÔÛ‹Ì·Ù·
¶›Ó·Î·˜ 1. √È Î˘ÚÈfiÙÂÚÔÈ ·Ú¿ÁÔÓÙ˜ Ô˘ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙËÓ ·ıÔÊ˘ÛÈÔÏÔÁ›· Ù˘ ÚÂ˘Ì·ÙÔÂȉԇ˜ ·ÚıÚ›Ùȉ·˜
°ÂÓÂÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ HLA-DR4, PTPN22, PAD14, CTLA-4, FcÁRs, ˘Ô‰Ô¯Â›˜ ΢ÙÙ·ÚÔÎÈÓÒÓ (TNF, IL-1, IL-10, IL-18) Î.¿. ¶ÂÚÈ‚·ÏÏÔÓÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ ªÈÎÚÔ-ÔÚÁ·ÓÈÛÌÔ›, οÓÈÛÌ·, stress ∞ÓÔÛÔÏÔÁÈÎÔ› ·Ú¿ÁÔÓÙ˜ Th17 ·ÙÙ·Ú· ∂ÓÂÚÁÔÔ›ËÛË Ì·ÎÚÔÊ¿ÁˆÓ, ÈÓÔ‚Ï·ÛÙÒÓ, ÂÓ‰ÔıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ, μ ΢ÙÙ¿ÚˆÓ, ¤ÎÎÚÈÛË Î˘ÙÙ·ÚÔÎÈÓÒÓ (IL-17, TNF, IL-1, RANKL, GM-CSF, ÔÛÙÂÔÔÓÙ›ÓË Î.¿.) Î·È ÂÓÂÚÁÔÔ›ËÛË ¯ÔÓ- ‰ÚÔ΢ÙÙ¿ÚˆÓ Î·È ÔÛÙÂÔÎÏ·ÛÙÒÓ Δ Ú˘ıÌÈÛÙÈο ·ÙÙ·Ú· ¶ÔÈÔÙÈΤ˜ ‹/Î·È ÔÛÔÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ μ ·ÙÙ·Ú· ∞ÓÙÈÁÔÓÔ·ÚÔ˘Û›·ÛË, ·Ú·ÁˆÁ‹ ·˘ÙÔ-·ÓÙÈÛˆÌ¿ÙˆÓ (RFs, anti-CCPs, anti-GP39 Î.¿.), ¤ÎÎÚÈ- ÛË Î˘ÙÙ·ÚÔÎÈÓÒÓ ª·ÎÚÔÊ¿Á· ∂ÓÂÚÁÔÔ›ËÛË ÈÓÔ‚Ï·ÛÙÒÓ, ÂÓ‰ÔıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ, ¤ÎÎÚÈÛË TNFa, IL-1 Î.¿. ™˘ÓÔ‚È·ÎÔ› ÈÓÔ‚Ï¿ÛÙ˜ ŒÎÎÚÈÛË PGE2, MMPs, IL-6, ÂÓÂÚÁÔÔ›ËÛË Ì·ÎÚÔÊ¿ÁˆÓ, μ ΢ÙÙ¿ÚˆÓ Î.¿. ÃÔÓ‰ÚÔ·ÙÙ·Ú· ¶·Ú·ÁˆÁ‹ ÎÔÏÏ·ÁÂÓ·ÛÒÓ, ÚˆÙÂÔÁÏ˘Î·ÓÒÓ, ·Ô‰fiÌËÛË ·ÚıÚÈÎÔ‡ ¯fiÓ‰ÚÔ˘ Î.¿. √ÛÙÂÔÎÏ¿ÛÙ˜ √ÛÙÈ΋ ‰È¿‚ÚˆÛË
ÛË Î˘ÙÙ·ÚÔÎÈÓÒÓ Î·È Î·Ù’ ¤ÎÙ·ÛË Ú‡ıÌÈÛ˘ Ù˘ ÔÛÙÂÔÎÏ·ÛÙÒÓ Î.¿. ·ÓÔÛȷ΋˜ ‰ÈÂÚÁ·Û›·˜. Δ· Ì·ÎÚÔÊ¿Á·, ˆ˜ Ú˘ıÌÈÛÙ¤˜ ™ÙËÓ Î·ı’ Ë̤ڷ Ú¿ÍË ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Û‹- Ù˘ ÂÓÂÚÁÔÔ›ËÛ˘ ÙˆÓ Û˘ÓÔ‚È·ÎÒÓ ÈÓÔ‚Ï·ÛÙÒÓ Î·È ÌÂÚ· Î·È ¿ÏÏÔÈ ‚ÈÔÏÔÁÈÎÔ› ·Ú¿ÁÔÓÙ˜, Ô˘ ÛÙԯ‡- ˆ˜ ·ÚÈ· ËÁ‹ TNF Î·È IL-1, ˘ÔÛÙËÚ›˙ÂÙ·È Ì¤¯ÚÈ Û‹- Ô˘Ó ÛÙ· μ ·ÙÙ·Ú· (·ÓÙÈ-CD20, rituximab) ‹ ÛÙË ÌÂÚ· fiÙÈ ¤¯Ô˘Ó ȉȷ›ÙÂÚË ı¤ÛË ÛÙËÓ ·ıÔÊ˘ÛÈÔÏÔÁ›· Û˘Ó-‰È¤ÁÂÚÛË, fiˆ˜ ÙÔ IgCTLA-4 ÌfiÚÈÔ (abatacept). Ù˘ ÓfiÛÔ˘, ·ÏÏ¿ Î·È ÛÙË ‰È·ÊÔÚÔÔ›ËÛË Ù˘ Δ Î˘Ù- ΔÂÏÂ˘Ù·›·, ÌÂÙ¿ ÙËÓ ·ÔÛ·Ê‹ÓÈÛË ÙÔ˘ ÚfiÏÔ˘ Ù˘ IL- Ù·ÚÈ΋˜ ÛÂÈÚ¿˜1. 6 ÛÙË ƒ∞ Î·È ÙËÓ Î·Ù¿‰ÂÈÍË ÙˆÓ Û˘ÛÙËÌ·ÙÈÎÒÓ ‰Ú¿- Ÿˆ˜ Ê·›ÓÂÙ·È, ÛÙËÓ ·ıÔÊ˘ÛÈÔÏÔÁ›· Ù˘ ƒ∞ ÛÂÒÓ Ù˘, ¯ÚËÛÈÌÔÔÈÂ›Ù·È ÌÔÓÔÎψÓÈÎfi ·Óٛۈ̷ Û˘ÌÌÂÙ¤¯ÂÈ ÏËıÒÚ· ΢ÙÙ¿ÚˆÓ, ÙfiÛÔ Ù˘ Ê˘ÛÈ΋˜ ¤Ó·ÓÙÈ ÙÔ˘ ˘Ô‰Ô¯¤· Ù˘ IL-6 (tocilizumab)3. fiÛÔ Î·È Ù˘ ÂȉÈ΋˜ ·ÓÔÛ›·˜, Ù· ÔÔ›· ·ÏÏËÏÂȉÚÔ‡Ó Ì¤Ûˆ ΢ÙÙ·ÚÔÎÈÓÒÓ Î·È ¯ËÌÂÈÔÎÈÓÒÓ, ÔÈ ÛËÌ·ÓÙÈÎfiÙÂ- ™˘ÛÙËÌ·ÙÈÎfi˜ ÂÚ˘ıËÌ·Ù҉˘ χÎÔ˜ Ú˜ ·fi ÙȘ Ôԛ˜ ·ÔÙÂÏÔ‡Ó Û‹ÌÂÚ· Ó¤Ô˘˜ ıÂÚ·- (™∂§) ¢ÙÈÎÔ‡˜ ÛÙfi¯Ô˘˜. ∏ ·Ó¿Ù˘ÍË ÙˆÓ ·ÓÙÈ-TNF ·Ú·- ÁfiÓÙˆÓ (etanercept, infliximab, adalimumab, golimu- √ ™∂§ ·ÔÙÂÏ› ÙÔ ÚfiÙ˘Ô ÙˆÓ Û˘ÛÙËÌ·ÙÈÎÒÓ ·˘- mab Î.¿.) ÛÙËÚ›¯ıËΠÛÙËÓ ·ÔÛ·Ê‹ÓÈÛË ÙÔ˘ ÚfiÏÔ˘ ÙÔ·ÓfiÛˆÓ ÓÔÛËÌ¿ÙˆÓ. ∏ ·ÈÙÈÔ·ıÔÁ¤ÓÂÈ· Ù˘ ÓfiÛÔ˘ ÙÔ˘ TNF ÛÙËÓ ·ıÔÊ˘ÛÈÔÏÔÁ›· Ù˘ ƒ∞, fiˆ˜ Ë Â·- Â›Ó·È ¿ÁÓˆÛÙË Î·È Ë Â›ÙˆÛ‹ Ù˘ ÂÚ›Ô˘ 0,05% ÁˆÁ‹ ÚÔÊÏÂÁÌÔÓˆ‰ÒÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ Î·È ¯ËÌÂÈÔÎÈ- ÛÙÔÓ ÁÂÓÈÎfi ÏËı˘ÛÌfi. ÷ڷÎÙËÚÈÛÙÈÎfi Ù˘ ÓfiÛÔ˘ ÓÒÓ, Ë ÂÓÂÚÁÔÔ›ËÛË ÂÓ‰ÔıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ, Ë ÓÂÔ- Â›Ó·È Ë ÂÓÙ˘ˆÛȷ΋ ÎÏÈÓÈ΋ ÂÙÂÚÔÁ¤ÓÂÈ· Î·È Ë ÏËıÒ- ·ÁÁÂÈÔÁ¤ÓÂÛË, Ë ÂÓÂÚÁÔÔ›ËÛË ¯ÔÓ‰ÚÔ΢ÙÙ¿ÚˆÓ Î·È Ú· ÙˆÓ ÂÚÁ·ÛÙËÚÈ·ÎÒÓ-·ÓÔÛÔÏÔÁÈÎÒÓ Â˘ÚËÌ¿ÙˆÓ. ∏
¶›Ó·Î·˜ 2. √È Î˘ÚÈfiÙÂÚÔÈ ·Ú¿ÁÔÓÙ˜ Ô˘ ÂÌϤÎÔÓÙ·È ÛÙËÓ ·ıÔÁ¤ÓÂÛË ÙÔ˘ Û˘ÛÙËÌ·ÙÈÎÔ‡ ÂÚ˘ıËÌ·ÙÒ‰Ô˘˜ χÎÔ˘
°ÂÓÂÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ HLA-DR2, -DR3, PDCD1, PTPN22, STAT4, IRF5, FcgRIIA, FcgRIIIA Î.¿. ¶ÂÚÈ‚·ÏÏÔÓÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ ªÈÎÚÔÔÚÁ·ÓÈÛÌÔ›, ˘ÂÚÈ҉˘ ·ÎÙÈÓÔ‚ÔÏ›·, Ê¿Ú̷η (ÚÔη˚Ó·Ì›‰Ë, ˘‰Ú·Ï·˙›ÓË, ÈÛÔÓÈ·˙›‰Ë, Ê·ÈÓ˘ÙÔ˝ÓË, ÂÓÈÎÈÏÏ·Ì›ÓË, ·ÓÙÈ-TNF Î.¿.), ‰È·ÈÙËÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ √ÚÌÔÓÈÎÔ› ·Ú¿ÁÔÓÙ˜ ¢È·Ù·Ú·¯‹ ÈÛÔÚÚÔ›·˜ ÔÈÛÙÚÔÁfiÓˆÓ-·Ó‰ÚÔÁfiÓˆÓ ∞ÓÔÛÔÏÔÁÈÎÔ› ·Ú¿ÁÔÓÙ˜ T ·ÙÙ·Ú· ∞˘ÍË̤ÓË ÂÓÂÚÁÔÔ›ËÛË (·˘ÍË̤ÓË ÂÓ‰Ô΢ÙÙ¿ÚÈ· Û˘ÁΤÓÙÚˆÛË Ca2+, ·˘ÍË̤ÓË ÂÓ‰Ô΢ÙÙ¿ÚÈ· ʈÛÊÔÚ˘Ï›ˆÛË, ˘ÂÚ¤ÎÊÚ·ÛË FcRÁ, ˘ÂÚ¤ÎÊÚ·ÛË CD40L), ·ÓÙ›ÛÙ·ÛË Û ·fiÙˆÛË Î.¿. Δ Ú˘ıÌÈÛÙÈο ·ÙÙ·Ú· ¶ÔÈÔÙÈΤ˜ ‹/Î·È ÔÛÔÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ μ ·ÙÙ·Ú· ∞˘ÍË̤ÓÔ˜ ·ÚÈıÌfi˜ Ï·ÛÌ·ÙÔ΢ÙÙ¿ÚˆÓ, ·˘ÍË̤ÓË Â˘·ÈÛıËÛ›· Û ÔÏ˘ÎψÓÈ΋ ÂÓÂÚÁÔÔ›Ë- ÛË ·fi ÂȉÈο ·ÓÙÈÁfiÓ·, ·˘ÍË̤ÓË ¤ÎÊÚ·ÛË ÌÔÚ›ˆÓ Û˘Ó-‰È¤ÁÂÚÛ˘, ·Ú·ÁˆÁ‹ ·˘ÙÔ·ÓÙÈÛˆ- Ì¿ÙˆÓ ª·ÎÚÔÊ¿Á·/º·ÁÔ·ÙÙ·Ú· ∂Ï·Ùو̤ÓË Ê·ÁÔ΢ÙÙ·ÚÈ΋ ‰Ú·ÛÙËÚÈfiÙËÙ·, ÂÏ·Ùو̤ÓË ·Ú·ÁˆÁ‹ ˘ÂÚÔÍÂȉ›ˆÓ, ÂÏ·Ùو̤- ÓË ¤ÎÊÚ·ÛË ÈÛÔ-ÂÓ˙‡ÌˆÓ ÚˆÙÂ˚ÓÈ΋˜ ÎÈÓ¿Û˘ C Î.¿. ¢ÂÓ‰ÚÈÙÈο ·ÙÙ·Ú· ∂ÂÍÂÚÁ·Û›· Î·È ·ÚÔ˘Û›·ÛË ·ÓÙÈÁfiÓˆÓ, ÂÓÂÚÁÔÔ›ËÛË Δ Î·È μ ΢ÙÙ¿ÚˆÓ, ¤ÎÎÚÈÛË IFN· Î.¿. K. ΔÛ¤ÏÈÔ˜ 37
‰È¿ÁÓˆÛË ÛÙËÚ›˙ÂÙ·È ÛÙ· ÙÚÔÔÔÈË̤ӷ ÎÚÈÙ‹ÚÈ· ŸÛÔÓ ·ÊÔÚ¿ ÛÙ· μ ÏÂÌÊÔ·ÙÙ·Ú·, Ê·›ÓÂÙ·È fiÙÈ ÙÔ˘ ∞ÌÂÚÈηÓÈÎÔ‡ ∫ÔÏÂÁ›Ô˘ ƒÂ˘Ì·ÙÔÏÔÁ›·˜ (1997). ˘¿Ú¯Ô˘Ó ÂÓ‰ÔÁÂÓ›˜ ‰È·Ù·Ú·¯¤˜, fiˆ˜ ·˘ÍË̤ÓË ∏ ·ıÔÁ¤ÓÂÛË Ù˘ ÓfiÛÔ˘ Û˘Ó›ÛÙ·Ù·È ÛÙËÓ ·ÏÏË- ¢·ÈÛıËÛ›· Û ÔÏ˘ÎψÓÈ΋ ÂÓÂÚÁÔÔ›ËÛË, ·˘ÍË̤ÓË Ï›‰Ú·ÛË ÁÂÓÂÙÈÎÒÓ, ÔÚÌÔÓÈÎÒÓ Î·È ÂÚÈ‚·ÏÏÔÓÙÈ- ¤ÎÊÚ·ÛË Û˘Ó-‰ÈÂÁÂÚÙÈÎÒÓ ÌÔÚ›ˆÓ Î·È ·Ú·ÁˆÁ‹ ÏË- ÎÒÓ ·Ú·ÁfiÓÙˆÓ, ÔÈ ÔÔ›ÔÈ Ô‰ËÁÔ‡Ó Û ÂÎÙÚÔ‹ ÙÔ˘ ıÒÚ·˜ ·˘ÙÔ-·ÓÙÈÛˆÌ¿ÙˆÓ Ì ·Ô‰Â‰ÂÈÁ̤ÓË ‹ ÌË ·ÓÔÛÈ·ÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ Ì ‰È·Ù·Ú·¯¤˜ Ô˘ ÂÓÙÔ›- Û˘ÌÌÂÙÔ¯‹ ÛÙËÓ ÚfiÎÏËÛË ÈÛÙÈ΋˜ ‚Ï¿‚˘. ˙ÔÓÙ·È ÙfiÛÔ ÛÂ Δ Î·È μ ÏÂÌÊÔ·ÙÙ·Ú·, fiÛÔ Î·È Û ∏ ÂÌÏÔ΋ Ù˘ Ê˘ÛÈ΋˜ ·ÓÔÛ›·˜ ¯·Ú·ÎÙËÚ›˙ÂÙ·È Î‡ÙÙ·Ú· Ù˘ Ê˘ÛÈ΋˜ ·ÓÔÛ›·˜, ηıÒ˜ Î·È Û ‰È·Ù·- ·fi ÙË Û˘ÌÌÂÙÔ¯‹ ÙˆÓ ‰ÂÓ‰ÚÈÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ ÛÙËÓ Ú·¯¤˜ Ù˘ ·fiÙˆÛ˘, Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·Ú·Áˆ- ·ıÔÊ˘ÛÈÔÏÔÁ›· Ù˘ ÓfiÛÔ˘, Ì ÙËÓ ¤ÎÎÚÈÛË IFN· Î·È Á‹ ·˘ÙÔ-·ÓÙÈۈ̿وÓ, ·ÓÔÛÔÛ˘ÌÏÂÁÌ¿ÙˆÓ Î·È, ÙÂÏÈ- Ù˘ Ú‡ıÌÈÛ˘ Ù˘ ·ÓÔÛȷ΋˜ ·fiÎÚÈÛ˘ ÛÂ Â›Â‰Ô Î¿, ÈÛÙÈ΋˜ ‚Ï¿‚˘. ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ. ∏ Û˘Ì‚ÔÏ‹ ÙˆÓ ÁÂÓÂÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ Â›Ó·È È‰È- √È ‰È·Ù·Ú·¯¤˜ ÙˆÓ Ê·ÁÔ΢ÙÙ¿ÚˆÓ ·ÊÔÚÔ‡Ó, ΢- ·›ÙÂÚ· ÈÛ¯˘Ú‹ ÛÙÔ ™∂§. ¡ÂfiÙÂÚ˜ ÌÂϤÙ˜ ¢Ú›·˜ Ú›ˆ˜, ÛÙËÓ ÂÏ·Ùو̤ÓË ¤ÎÊÚ·ÛË ÌÔÚ›ˆÓ Ô˘ ÂÌϤ- ÁÂÓˆÌÈ΋˜ ·Ó¿Ï˘Û˘ η٤‰ÂÈÍ·Ó ÁÔÓȉȷÎÔ‡˜ ÙfiÔ˘˜ ÎÔÓÙ·È ÛÙË ‰È·‰Èηۛ· Ù˘ Ê·ÁÔ΢ÙÙ¿ÚˆÛ˘ ·ÔÙˆ- (HLA-DR2, -DR3, PDCD1, PTPN22, STAT4, IRF5, ÙÈÎÔ‡ ˘ÏÈÎÔ‡. ∏ ‰È·‰Èηۛ· Ù˘ ·fiÙˆÛ˘ ÂÌϤÎÂ- FcgRIIA, FcgRIIIA Î.¿.), Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÚԉȿıÂ- Ù·È ÛÙËÓ ·ıÔÁ¤ÓÂÛË Ù˘ ÓfiÛÔ˘ ̤ۈ Ù˘ ‰ËÌÈÔ˘Ú- ÛË Û ·Ó¿Ù˘ÍË ÓfiÛÔ˘, ηıÒ˜ Î·È ÙË ÏÂÈÙÔ˘ÚÁÈ΋ Á›·˜ ÓÂÔÂÈÙfiˆÓ ‹ ÙËÓ ÂÌÊ¿ÓÈÛË ÎÚ˘ÙÈÎÒÓ ÂÈÙfi- ÙÔ˘˜ ÛËÌ·Û›·. ∏ ÏÂÈÙÔ˘ÚÁÈ΋ ¤ÎÊÚ·ÛË ÙˆÓ ÁÔÓȉ›ˆÓ ˆÓ, ÙË ‰ËÌÈÔ˘ÚÁ›· ·ÓÙÈÛˆÌ¿ÙˆÓ Î·È ·ÓÔÛÔÛ˘ÌÏÂÁ- ·˘ÙÒÓ ÂÓۈ̷ÙÒıËΠÛÙÔ ÚfiÛÊ·ÙÔ ·ıÔÊ˘ÛÈÔÏÔ- Ì¿ÙˆÓ. ™ÙË ‰È·‰Èηۛ· Ê·›ÓÂÙ·È Ó· Û˘ÌÌÂÙ¤¯Ô˘Ó Î·È ÁÈÎfi ÌÔÓÙ¤ÏÔ Ù˘ ÓfiÛÔ˘4. ¿ÏÏÔÈ ·Ú¿ÁÔÓÙ˜ fiˆ˜ ÔÈ TLR ˘Ô‰Ô¯Â›˜, Ë ·˘ÍË- ∏ Û˘Ì‚ÔÏ‹ ÙˆÓ ÂÚÈ‚·ÏÏÔÓÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ, ̤ÓË ¤ÎÊÚ·ÛË ÌÔÚ›ˆÓ ÚÔÛÎfiÏÏËÛ˘ ‹ Î·È ÂÓ‰ÔÁÂ- ΢ڛˆ˜ Ù˘ ˘ÂÚÈÒ‰Ô˘˜ ·ÎÙÈÓÔ‚ÔÏ›·˜, ÙˆÓ Ê·ÚÌ¿ÎˆÓ Ó›˜ ‰È·Ù·Ú·¯¤˜ ÙˆÓ CD4+ Δ Î˘ÙÙ¿ÚˆÓ. Î·È ‰È·ÊfiÚˆÓ ·ıÔÁfiÓˆÓ ÌÈÎÚÔ-ÔÚÁ·ÓÈÛÌÒÓ, ıˆÚ›- √È ÓÂfiÙÂÚ˜ ıÂڷ¢ÙÈΤ˜ ÚÔÛÂÁÁ›ÛÂȘ ÛÙÔ Ù·È È‰È·›ÙÂÚ· ÛËÌ·ÓÙÈ΋ ÛÙËÓ ·ıÔÁ¤ÓÂÛË Ù˘ ÓfiÛÔ˘. ™∂§ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÌfiÚÈ·, Ù· ÔÔ›· ÛÙÔ¯Â‡Ô˘Ó √È ÔÚÌÔÓÈÎÔ› ·Ú¿ÁÔÓÙ˜ Ê·›ÓÂÙ·È Ó· ·›˙Ô˘Ó ÛÙÔÓ ¤ÏÂÁ¯Ô Ù˘ ÔÏ˘ÎψÓÈ΋˜ ÂÓÂÚÁÔÔ›ËÛ˘ ÙÔ˘ μ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ·ıÔÁ¤ÓÂÛË ·ÏÏ¿ Î·È ÛÙËÓ ÎÏÈ- ΢ÙÙ¿ÚÔ˘ (anti-CD20, rituximab, anti-CD22, ocreli- ÓÈ΋ ¤ÎÊÚ·ÛË Ù˘ ÓfiÛÔ˘. ΔÔÓ›˙ÔÓÙ·È ÔÈ ÂÈ‚·Ú˘ÓÙÈΤ˜ zumab, atacicept), ηıÒ˜ Î·È ÛÙË Û˘Ó‰È¤ÁÂÚÛË (aba- ÂȉڿÛÂȘ ÙˆÓ ÔÈÛÙÚÔÁfiÓˆÓ, ÂÓ‰ÔÁÂÓÒÓ ‹ Â͈ÁÂ- tacept)5. ¶·Ú¿ÏÏËÏ·, Û ʿÛË ÎÏÈÓÈÎÒÓ ÌÂÏÂÙÒÓ ‚Ú›- ÓÒÓ, ηıÒ˜ Î·È Ë ÚÔÊ˘Ï·ÎÙÈ΋ ‰Ú¿ÛË ÙˆÓ ·Ó‰ÚÔ- ÛÎÔÓÙ·È Î·È ·Ú¿ÁÔÓÙ˜ Ô˘ ÛÙÔ¯Â‡Ô˘Ó Û ΢ÙÙ·ÚÔ- ÁfiÓˆÓ. ΛÓ˜, fiˆ˜ Ë IFN· Î·È Ë IL-10. ∏ ‰È¿Û·ÛË Ù˘ ·ÓÔÛȷ΋˜ ·ÓÔ¯‹˜, ȉ›ˆ˜ Ù˘ ÂÚÈÊÂÚÈ΋˜, ÂÎÊÚ¿˙ÂÙ·È Ì ÙËÓ ·ÚÔ˘Û›·ÛË ÎÚ˘ÙÈ- μÈ‚ÏÈÔÁÚ·Ê›· ÎÒÓ ÂÈÙfiˆÓ ‹ ÓÂÔÂÈÙfiˆÓ, ÙËÓ ·ıÔÏÔÁÈ΋ ÂÂ- 1. McInnes IB, Schett G. Cytokines in the pathogenesis of ÍÂÚÁ·Û›· ·ÓÙÈÁfiÓˆÓ, ·ÏÏ¿ Î·È ÙËÓ ÔÈÔÙÈ΋ ‹/Î·È Ô- rheumatoid arthritis. Nat Rev Immunol 2007; 7: 429-42. ÛÔÙÈ΋ ‰È·Ù·Ú·¯‹ ÙˆÓ CD4+CD25high Δ Ú˘ıÌÈÛÙÈÎÒÓ 2. Takayanagi H. Osteoimmunology: shared mechanisms and ΢ÙÙ¿ÚˆÓ. ø˜ ·ÔÙ¤ÏÂÛÌ·, ¿ÁÂÙ·È ·ıÔÏÔÁÈ΋ crosstalk between the immune and bone systems. Nat ·ÓÔÛȷ΋ ·fiÎÚÈÛË ÌÂ Û˘ÌÌÂÙÔ¯‹ ÏËıÒÚ·˜ ·ÓÔ- Rev Immunol 2007; 7: 292-304. ÛÔ˚ηÓÒÓ Î˘ÙÙ¿ÚˆÓ Î·È Î˘ÙÙ·ÚÔÎÈÓÒÓ. 3. Fonseca JE, Santos MJ, Canhao H, et al. IL-6 as a key player in systemic inflammation and joint destruction. Autoi- √È ‰È·Ù·Ú·¯¤˜ ÙˆÓ Δ Î˘ÙÙ¿ÚˆÓ, ÙfiÛÔ ÙˆÓ mmun Rev 2009; 8: 538-42. CD4+ fiÛÔ Î·È ÙˆÓ CD8+, ÛÙË ÓfiÛÔ Û˘Ó›ÛÙ·ÓÙ·È 4. Crow MK. Collaboration, genetic associations and lupus ery- ÛÙËÓ ·˘ÍË̤ÓË ÂÓÂÚÁÔÔ›ËÛ‹ ÙÔ˘˜ (·˘ÍË̤ÓË ÂÓ‰Ô- thematosus. N Engl J Med 2008; 358: 956-61. 2+ ΢ÙÙ¿ÚÈ· Û˘ÁΤÓÙÚˆÛË Ca , ·˘ÍË̤ÓË ÂÓ‰Ô΢ÙÙ¿ÚÈ· 5. Isenberg DA. Treating patients with lupus with B cell deple- ʈÛÊÔÚ˘Ï›ˆÛË, ˘ÂÚ¤ÎÊÚ·ÛË FcRÁ, ˘ÂÚ¤ÎÊÚ·ÛË tion. Lupus 2008; 17: 400-4. CD40L, ·ÓÙ›ÛÙ·ÛË Û ·fiÙˆÛË Î.¿.). ¶·Ú¿ÏÏËÏ·, ηٷ‰ÂÈÎÓ‡ÂÙ·È Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ‰È·Ù·Ú·¯‹ ÛÙÔ ∞ÏÏËÏÔÁÚ·Ê›·: Â›Â‰Ô ÙˆÓ Ê˘ÛÈÎÒÓ Ú˘ıÌÈÛÙÈÎÒÓ Δ Î˘ÙÙ¿ÚˆÓ. E-mail: [email protected] ∞˘ÙÔ¿ÓÔÛ· ÓÔÛ‹Ì·Ù·
√ÚÁ·ÓÔÂȉÈο ∞˘ÙÔ¿ÓÔÛ· ¡ÔÛ‹Ì·Ù·
∞. ΔÛÈÚÔÁÈ¿ÓÓË
ΔÌ‹Ì· ∞ÓÔÛÔÏÔÁ›·˜ – πÛÙÔÛ˘Ì‚·ÙfiÙËÙ·˜ °¡∞ «√ ∂˘·ÁÁÂÏÈÛÌfi˜»
2009; 1: 38 – 42
Δ· ÔÚÁ·ÓÔÂȉÈο ·˘ÙÔ¿ÓÔÛ· ÓÔÛ‹Ì·Ù· ¯·Ú·ÎÙËÚ›- ı˘ÚÂÔÂȉÈÎÒÓ ·ÓÙÈÛˆÌ¿ÙˆÓ (∞£∞) Î·È ÎÏÈÓÈο ·fi ÙË ˙ÔÓÙ·È ·fi ÙËÓ ·ÚÔ˘Û›· ·˘ÙÔ·ÓÙȉÚÒÓÙˆÓ ÎÏÒÓˆÓ ‰È·Ù·Ú·¯‹ Ù˘ ÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ ı˘ÚÂÔÂȉԇ˜ ·‰¤Ó· Δ ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ Î·È ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ Ô˘ ·ÓÙÈ- (˘Ôı˘ÚÂÔÂȉÈÛÌfi˜ ÛÙË ∏Δ, ˘ÂÚı˘ÚÂÔÂȉÈÛÌfi˜ ÛÙË ‰ÚÔ‡Ó Ì ·ÓÙÈÁfiÓ· ÂÓfi˜ ÔÚÁ¿ÓÔ˘ Î·È ÂÎÊÚ¿˙ÂÙ·È ÎÏÈ- GD). ÕÏϘ ÏÈÁfiÙÂÚÔ Û˘¯Ó¤˜ ÌÔÚʤ˜ Ù˘ ÓfiÛÔ˘ ›- ÓÈο Ì ·ıÔÏÔÁ›· ÙÔ˘ ›‰ÈÔ˘ ÔÚÁ¿ÓÔ˘. ™Ù· ÓÔÛ‹Ì·Ù· Ó·È Ë ·ÙÚÔÊÈ΋ ı˘ÚÂÔÂȉ›Ùȉ·, Ë ı˘ÚÂÔÂȉ›Ùȉ· ÌÂÙ¿ ·˘Ù¿ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È Î˘Ú›ˆ˜ ÂÓ‰ÔÎÚÈÓÔ¿ıÂȘ (·˘- ·fi ÙÔÎÂÙfi ‹ ÌÂÙ¿ ·fi Ï‹„Ë Ê·ÚÌ¿ÎˆÓ fiˆ˜ ÈÓÙÂÚ- ÙÔ¿ÓÔÛË ı˘ÚÂÔÂȉ›Ùȉ·, ۷ί·Ú҉˘ ‰È·‚‹Ù˘ Ù‡- ÊÂÚfiÓË, ηıÒ˜ Î·È Ë ı˘ÚÂÔÂȉ›Ùȉ· Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì Ԣ 1, ÓfiÛÔ˜ Addison), ·ÏÏ¿ Î·È ÓÔÛ‹Ì·Ù· ÙÔ˘ ‰¤Ú- Ù· ÔÏ˘·‰ÂÓÈο Û‡Ó‰ÚÔÌ·. √È ‰È¿ÊÔÚ˜ ÌÔÚʤ˜ Ù˘ Ì·ÙÔ˜ (ÔÌÊÔÏ˘ÁÒ‰Ë), ÙÔ˘ ÎÂÓÙÚÈÎÔ‡ Î·È ÂÚÈÊÂÚÈ- ÓfiÛÔ˘ ··ÓÙÒÓÙ·È Ôχ Û˘¯Ó¿ Û ¿ÙÔÌ· Ù˘ ›‰È·˜ ÔÈ- ÎÔ‡ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ (ÛÎÏ‹Ú˘ÓÛË Î·Ù¿ Ͽη˜, ÎÔÁ¤ÓÂÈ·˜ Î·È Â›Ó·È Èı·Ófi ÛÙÔ ›‰ÈÔ ¿ÙÔÌÔ Ë Ì›· ÌÔÚ- ÂÚÈÊÂÚÈ΋ Ó¢ÚÔ¿ıÂÈ·), ÙÔ˘ ÂÙÈÎÔ‡ (·˘ÙÔ¿ÓÔÛË Ê‹ Ó· ÌÂÙ·¤ÛÂÈ Û ¿ÏÏË. ∂›Û˘ Ë ÓfiÛÔ˜ Û˘¯Ó¿ Û˘- Á·ÛÙÚ›Ùȉ·, ÎÔÈÏÈÔοÎË) Î·È ÙÔ˘ ‹·ÙÔ˜ (ÚˆÙÔ·ı‹˜ Ó˘¿Ú¯ÂÈ Ì ¿ÏÏ· ·˘ÙÔ¿ÓÔÛ· ÔÚÁ·ÓÔÂȉÈο ÓÔÛ‹Ì·- ¯ÔÏÈ΋ ΛÚÚˆÛË, ¯ÚfiÓÈ· ÂÓÂÚÁfi˜ Ë·Ù›Ùȉ·). Ù· fiˆ˜ ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË Ù‡Ô˘ 1, ÓfiÛÔ Addi- son, ÎÔÈÏÈÔοÎË, ·˘ÙÔ¿ÓÔÛË Á·ÛÙÚ›Ùȉ· ηıÒ˜ Î·È ÌË ∞˘ÙÔ¿ÓÔÛË £˘ÚÂÔÂȉ›Ùȉ· ÔÚÁ·ÓÔÂȉÈο fiˆ˜ χÎË, „ˆÚ›·ÛË, ÚÂ˘Ì·ÙÔÂȉ‹ 2,3 ∏ ·˘ÙÔ¿ÓÔÛ˘ ·ÈÙÈÔÏÔÁ›·˜ ı˘ÚÂÔÂȉÈ΋ ÓfiÛÔ˜ ·ÚıÚ›Ùȉ·, Ì˘·Ûı¤ÓÂÈ· . (ATD) ·ÔÙÂÏ› ÙË Û˘¯ÓfiÙÂÚË ÔÚÁ·ÓÔÂȉÈ΋ ·˘ÙÔ¿- √È Ì˯·ÓÈÛÌÔ› Ô˘ ÂÌϤÎÔÓÙ·È ÛÙËÓ ·ıÔÁ¤- ÓÔÛË ‰È·Ù·Ú·¯‹ Î·È ÚÔÛ‚¿ÏÏÂÈ Î˘Ú›ˆ˜ ÙȘ Á˘Ó·›Î˜ ÓÂÈ· Ù˘ ATD ·ÔÙÂÏÔ‡Ó ·ÓÙÈΛÌÂÓÔ ÔÏÏÒÓ ÂÚ¢- (·Ó·ÏÔÁ›· °/∞ 10:1). ∞fi ÌÂÁ¿Ï˜ ÂȉËÌÈÔÏÔÁÈΤ˜ ÓÒÓ Ô˘ Û˘ÁÎÏ›ÓÔ˘Ó ÛÙËÓ ˘fiıÂÛË fiÙÈ Ë ·ÏÏËÏ›- ÌÂϤÙ˜, ÎÏÈÓÈο ¤Î‰ËÏË ATD ÂÌÊ·Ó›˙ÂÙ·È ÛÙÔ 2% ÙˆÓ ‰Ú·ÛË ÙˆÓ ÂÚÈ‚·ÏÏÔÓÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ Ì ÙÔ ÁÂÓÂ- Á˘Ó·ÈÎÒÓ ÂÓÒ Ë Û˘¯ÓfiÙËÙ· Ù˘ ˘ÔÎÏÈÓÈ΋˜ ÓfiÛÔ˘, ÙÈÎfi ˘fiÛÙڈ̷ ÙÔ˘ ·ÙfiÌÔ˘ Ê·›ÓÂÙ·È Ó· ·›˙ÂÈ ÙÔÓ fiˆ˜ ·˘Ù‹ ÔÚ›˙ÂÙ·È ·fi ÙËÓ ·ÚÔ˘Û›· ·ÓÙÈı˘ÚÂÔÂÈ- ηıÔÚÈÛÙÈÎfi ÚfiÏÔ ÛÙËÓ ÂÌÊ¿ÓÈÛË Ù˘ ATD. ŒÙÛÈ, ‰ÈÎÒÓ ·ÓÙÈÛˆÌ¿ÙˆÓ Û ¢ı˘ÚÂÔÂȉÈο ¿ÙÔÌ·, Â›Ó·È ÛÙÔ˘˜ ÂÚÈ‚·ÏÏÔÓÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ ÂÚÈÏ·Ì‚¿ÓÔ- ÂÚ›Ô˘ ‰ÂηϿÛÈ·1,4. ÓÙ·È ÙÔ Î¿ÓÈÛÌ·, ÙÔ stress, Ë ÚfiÛÏË„Ë Èˆ‰›Ô˘, Ë ∏ Ù·ÍÈÓfiÌËÛË Ù˘ ATD ÂÚÈÏ·Ì‚¿ÓÂÈ ‰‡Ô ΢- ·Ó¿ÚÎÂÈ· ÛÂÏËÓ›Ô˘, ‰È¿ÊÔÚ· Ê¿Ú̷η, Ë ·ÎÙÈÓÔ- Ú›ˆ˜ ÎÏÈÓÈΤ˜ ÔÓÙfiÙËÙ˜, ÙË ı˘ÚÂÔÂȉ›Ùȉ· Hashimo- ‚ÔÏ›·, ÈÔÁÂÓ›˜ Î·È ‚·ÎÙËÚȷΤ˜ ÏÔÈÌÒÍÂȘ, Ë ·ÏÏÂÚÁ›·, to’s (HT) Î·È ÙË ÓfiÛÔ Graves’ (GD),, ÔÈ Ôԛ˜ ¯·- Ë Î‡ËÛË Î·È Ë Ïԯ›·. ¶ÔÈΛϷ ÁÔÓ›‰È· ÙÔ˘ MHC, Ú·ÎÙËÚ›˙ÔÓÙ·È ÈÛÙÔ·ıÔÏÔÁÈο ·fi ‰È‹ıËÛË ÙÔ˘ ·- HLA-μ8 Î·È -DR3 (DRB1*03) Û˘Û¯ÂÙ›˙ÔÓÙ·È Ì ÙËÓ ÚÂί‡Ì·ÙÔ˜ ÙÔ˘ ı˘ÚÂÔÂȉԇ˜ ·‰¤Ó· ·fi Δ Î·È μ ÂÌÊ¿ÓÈÛË Ù˘ GD Ì ۯÂÙÈÎfi ΛӉ˘ÓÔ 3-4 ÛÙÔ˘˜ ∫·˘- ÏÂÌÊÔ·ÙÙ·Ú·, ÔÚÔÏÔÁÈο ·fi ÙËÓ ·Ú·ÁˆÁ‹ ·ÓÙÈ- οÛÈÔ˘˜, ÂÓÒ ˘¿Ú¯Ô˘Ó ·Ó·ÊÔÚ¤˜ ÁÈ· Û˘Û¯¤ÙÈÛË ÙˆÓ ∞. TÛÈÚÔÁÈ¿ÓÓË 39
∂ÈÎ. 1. ∞ÓÔÛÔ·ıÔÁÂÓÂÙÈÎÔ› Ì˯·ÓÈÛÌÔ› ÛÙËÓ ·˘ÙÔ¿ÓÔÛË ı˘ÚÂÔÂȉÈ΋ ÓfiÛÔ.
HLA-DR3, DR4 Î·È DQw7 (DQB1*0301) Ì HT ÎÙÈÎfi ¿ÙÔÌÔ ı· Ô‰ËÁ‹ÛÂÈ ÛÙËÓ ¤ÎÙÔË ¤ÎÊÚ·ÛË ÙˆÓ ÛÙÔÓ ›‰ÈÔ ÏËı˘ÛÌfi. Δ¤ÏÔ˜, ÔÏ˘ÌÔÚÊÈÛÌÔ› ¿ÏÏˆÓ HLA Ù¿Í˘ ππ ÛÙ· ı˘ÚÂÔÂȉÈο ·ÙÙ·Ú· Ì ·ÔÙ¤ÏÂ- ÁÔÓȉ›ˆÓ Ô˘ Έ‰ÈÎÔÔÈÔ‡Ó ÁÈ· CTLA-4, CD40, ÛÌ· ÙËÓ ·ÓÙÈÁÔÓÔ·ÚÔ˘Û›·ÛË ÛÙ· CD4 ÏÂÌÊÔ·ÙÙ·- PTPN22, ı˘ÚÂÔÛÊ·ÈÚ›ÓË Î·È ˘Ô‰Ô¯¤· Ù˘ TSH ¤- Ú·, ÙËÓ ÂÓÂÚÁÔÔ›ËÛ‹ ÙÔ˘˜, ÙËÓ ¤ÎÎÚÈÛË IFN-Á Ì ¯Ô˘Ó Û˘Û¯ÂÙÈÛı› Ì ÙËÓ ÂȉÂÎÙÈÎfiÙËÙ· ‹ ÙËÓ ·ıÔ- ·ÎfiÏÔ˘ıÔ ÙËÓ ¤ÎÊÚ·ÛË ÌÔÚ›ˆÓ Fas Î·È Î·Û·ÛÒÓ Á¤ÓÂÈ· Ù˘ GD Î·È Ù˘ HT2-4. Ì ÙÂÏÈÎfi ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·˘ÙÔÎÙÔÓ›· ‹ ·‰ÂÏÊÔÎÙÔÓ›· ∏ ı˘ÚÂÔÂȉ›Ùȉ· Hashimoto’s (HT) Â›Ó·È Ì›· Ù˘- ÙˆÓ ı˘ÚÂÔÂȉÈÎÒÓ Î˘ÙÙ¿ÚˆÓ. ¶·Ú¿ÏÏËÏ·, Ë ÂÓÂÚÁÔ- È΋ Δ Î˘ÙÙ·ÚÈ΋ ‰È·ÌÂÛÔÏ·‚Ô‡ÌÂÓË ·˘ÙÔ¿ÓÔÛË Ófi- Ô›ËÛË Ì¤Ûˆ IL-2 ÙˆÓ CD8 ΢ÙÙ·ÚÔÙÔÍÈÎÒÓ ÏÂÌÊÔ- ÛÔ˜, Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi Th1 Ù‡Ô˘ ·ÓÔÛȷ΋ ΢ÙÙ¿ÚˆÓ ·ÏÏ¿ Î·È Ë ·Ú·ÁˆÁ‹ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ı· ·¿ÓÙËÛË, ¤ÓÙÔÓË ÏÂÌÊÔ΢ÙÙ·ÚÈ΋ ‰È‹ıËÛË Ô˘ Ô‰Ë- Ô‰ËÁ‹ÛÂÈ Û ·fiÙˆÛË ‹ Ó¤ÎÚˆÛË ÙˆÓ ı˘ÚÂÔÂȉÈÎÒÓ Á› ÛÙËÓ Î·Ù·ÛÙÚÔÊ‹ ÙˆÓ ı˘ÚÂÔÂȉÈÎÒÓ ı˘Ï·Î›ˆÓ Ì ΢ÙÙ¿ÚˆÓ (ÂÚÊÔÚ›ÓË/granzyme Î·È ÂÓÂÚÁÔÔ›ËÛË Û˘- ·ÔÙ¤ÏÂÛÌ· ÙÔÓ ˘Ôı˘ÚÂÔÂȉÈÛÌfi. ∏ ›‰Ú·ÛË ÙˆÓ ÌÏËÚÒÌ·ÙÔ˜ ADCC ·ÓÙ›ÛÙÔȯ·). ∏ ÓfiÛÔ˜ Graves’ ÂÚÈ‚·ÏÏÔÓÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ Û ¤Ó· ÁÂÓÂÙÈο ÂȉÂ- (GD) ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi Th2 Ù‡Ô˘ ¯˘ÌÈ΋ ·ÓÔÛÈ·-
∂ÈÎ. 2. ∞ÓÔÛÔ·ıÔÁÂÓÂÙÈÎÔ› Ì˯·ÓÈÛÌÔ› ÛÙÔÓ ™·Î¯·ÚÒ‰Ë ¢È·‚‹ÙË Ù‡Ô˘ 1. 40 √ÚÁ·ÓÔÂȉÈο ·˘ÙÔ¿ÓÔÛ· ÓÔÛ‹Ì·Ù·
∂ÈÎ. 3. ªÔÓÙ¤ÏÔ ·ÓÔÛÔ·ıÔÁÂÓÂÙÈÎÒÓ Ì˯·ÓÈÛÌÒÓ ÛÙËÓ ÎÔÈÏÈÔοÎË.
΋ ·¿ÓÙËÛË, ÌÂÙÚ›Ô˘ ‚·ıÌÔ‡ ÏÂÌÊÔ΢ÙÙ·ÚÈ΋ ‰È‹ıË- ‰›ˆÓ ÙÔ˘ Langerhans, ÛÙËÓ ·Ó¿ÚÎÂÈ· ·Ú·ÁˆÁ‹˜ ÛË Î·È ·ÚÔ˘Û›· ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ Ô˘ ·ÛÎÔ‡Ó ‰ÈÂ- ÈÓÛÔ˘Ï›Ó˘ Î·È ÙËÓ ÎÏÈÓÈ΋ ÂΉ‹ÏˆÛË Û·Î¯·ÚÒ‰Ô˘˜ ÁÂÚÙÈ΋ ‰Ú¿ÛË ÛÙÔÓ ˘Ô‰Ô¯¤· Ù˘ ı˘ÚÂÔÙÚfiÔ˘ ÔÚ- ‰È·‚‹ÙË Û ÁÂÓÂÙÈο ÚԉȷÙÂıÂÈ̤ӷ ¿ÙÔÌ·. √ ÌfiÓ˘. ∏ ‰Ú¿ÛË Ù˘ IL-4 Î·È IL-10 Ô‰ËÁ› ÛÙËÓ ¤Î- ™¢Δ1 ·ÔÙÂÏ› ÌÈ· ·fi ÙȘ ÈÔ ÛÔ‚·Ú¤˜ Î·È Û˘¯Ó¤˜ ÊÚ·ÛË ·ÓÙÈ·ÔÙˆÙÈÎÒÓ ÌÔÚ›ˆÓ (cFLIP, BCL-XL) Ì ÌÂÙ·‚ÔÏÈΤ˜ ‰È·Ù·Ú·¯¤˜, ·ÊÔÚ¿ ΢ڛˆ˜ ·È‰È¿ Î·È ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÚÔÛÙ·Û›· Î·È ÂÈ‚›ˆÛË ÙˆÓ ı˘ÚÂÔ- Ó·ڿ ¿ÙÔÌ· Î·È ÚÔÛ‚¿ÏÏÂÈ ÂÚ›Ô˘ ¤Ó· ¿ÙÔÌÔ ÛÙ· ÂȉÈÎÒÓ Î˘ÙÙ¿ÚˆÓ. ∫ÏÈÓÈο Ë ÓfiÛÔ˜ ÂΉËÏÒÓÂÙ·È Ì 300 ÛÙȘ ∏¶∞, ÂÓÒ Û‡Ìʈӷ Ì ÂȉËÌÈÔÏÔÁÈΤ˜ ÌÂ- ˘ÂÚı˘ÚÂÔÂȉÈÛÌfi Î·È ÌÔÚ› Ó· Û˘Óԉ‡ÂÙ·È ·fi ϤÙ˜ Ë Â›ÙˆÛ‹ ÙÔ˘ ÛÙËÓ ∂˘ÚÒË Â›Ó·È ÌÂÁ·Ï‡ÙÂÚË. ‰˘Ûı˘ÚÂÔÂȉÈ΋ ÔÊı·ÏÌÔ¿ıÂÈ·1,4. √ Û˘Ó‰˘·ÛÌfi˜ Ù˘ ‰Ú¿Û˘ ÂÚÈ‚·ÏÏÔÓÙÈÎÒÓ ∏ ·ÚÔ˘Û›· ·˘ÙÔ·ÓÙÈۈ̿وÓ, ¤Ó·ÓÙÈ ı˘ÚÂÔ- Î·È ÁÂÓÂÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ Ê·›ÓÂÙ·È fiÙÈ ·ÔÙÂÏ› ÙËÓ ÛÊ·ÈÚ›Ó˘ (ÔÌÔ‰ÈÌÂÚ‹˜ ÚˆÙ½ÓË 660 kd, ‰Ú· ˆ˜ ·ÈÙ›· ÚfiÎÏËÛ˘ Ù˘ ÓfiÛÔ˘. ¢È¿ÊÔÚÔÈ ÈÔ›, fiˆ˜ Ô ÚÔ-ÔÚÌfiÓË) Î·È ¤Ó·ÓÙÈ ı˘ÚÂÔÂȉÈ΋˜ ˘ÂÚÔÍÂȉ¿- Coxsackie B, Ô Èfi˜ Ù˘ ÂÚ˘ıÚ¿˜, Ô CMV, Ô Epstein- Û˘ (‰È·ÌÂÌ‚Ú·ÓÈ΋ ÁÏ˘ÎÔÚˆÙ½ÓË 107 kd), ¯·Ú·- Barr, Ô Èfi˜ Ù˘ ·ÚˆÙ›Ùȉ·˜, Â›Ó·È ÌÂÚÈÎÔ› ·fi ÙÔ˘˜ ÎÙËÚ›˙ÂÈ Î·È ÙȘ ‰‡Ô ÌÔÚʤ˜ Ù˘ ATD Û ˘„ËÏ¿ Ô- ÏÔÈÌÒ‰ÂȘ ·Ú¿ÁÔÓÙ˜ Ô˘ ÂÌϤÎÔÓÙ·È ÛÙËÓ ·ıÔ- ÛÔÛÙ¿ (65-90%), ÂÓÒ Ù· ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙÔ˘ ˘Ô- Á¤ÓÂÈ· Ù˘ ÓfiÛÔ˘. ΔÂÏÂ˘Ù·›·, Ë ÌÂϤÙË Ù˘ ‰È·ÙÚÔÊÈ- ‰Ô¯¤· Ù˘ TSH ÂÌÊ·Ó›˙ÔÓÙ·È ÌfiÓÔ ÛÙË GD Û ÔÛÔ- ΋˜ Û˘Ó‹ıÂÈ·˜ ÙˆÓ ·ÛıÂÓÒÓ ·¤‰ÂÈÍ fiÙÈ Ë Ï‹„Ë ·ÁÂ- ÛÙfi 93-97% Î·È ‰È·ÎÚ›ÓÔÓÙ·È Û ‰ÈÂÁÂÚÙÈο, ·˘ÍËÙÈο Ï·‰ÈÓÔ‡ Á¿Ï·ÎÙÔ˜ ÚÈÓ ÙÔ 1Ô ¤ÙÔ˜ Ù˘ ˙ˆ‹˜ ÙˆÓ ·È- Î·È ‰ÂÛÌ¢ÙÈο ·Ó¿ÏÔÁ· Ì ÙË ‰Ú¿ÛË ÙÔ˘˜ › ÙÔ˘ ‰ÈÒÓ, Ë ·˘ÍË̤ÓË ÚfiÛÏË„Ë ÁÏÔ˘Ù¤Ó˘ ·ÏÏ¿ Î·È Ë ˘Ô‰Ô¯¤·. ∏ ·ÚÔ˘Û›· ∞£∞ Û ¢ı˘ÚÂÔÂȉÈο ¿ÙÔ- ÌÂȈ̤ÓË Ï‹„Ë ‚ÈÙ·Ì›Ó˘ D ·›˙Ô˘Ó ÛËÌ·ÓÙÈÎfi ÚfiÏÔ Ì· Û ÔÛÔÛÙfi 12-23% Î·È Î˘Ú›ˆ˜ Û ÂÁ·Ԣ˜, Û ÛÙËÓ ÂÌÊ¿ÓÈÛË Ù˘ ÓfiÛÔ˘. ∞fi ÙÔ˘˜ ÁÂÓÂÙÈÎÔ‡˜ ·- Û˘ÁÁÂÓ›˜ ·ÛıÂÓÒÓ Ì ATD ‹ ¿ÏÏË ·˘ÙÔ¿ÓÔÛË ÔÚÁ·- Ú¿ÁÔÓÙ˜ Ô˘ Û˘Ì‚¿ÏÏÔ˘Ó ÛÙËÓ ·ıÔÁ¤ÓÂÈ· Ù˘ Ófi- ÓÔÂȉÈ΋ ‹ Û˘ÛÙËÌ·ÙÈ΋ ÓfiÛÔ ˘Ô‰ËÏÒÓÂÈ ·˘ÍË̤ÓÔ ÛÔ˘ Â›Ó·È Ù· ÁÔÓ›‰È· Ô˘ ·ÊÔÚÔ‡Ó Ù· HLA Ù¿Í˘ ππ ΛӉ˘ÓÔ ÂΉ‹ÏˆÛ˘ ÓfiÛÔ˘ Î·È ¯Ú‹˙ÂÈ ·Ú·ÎÔÏÔ‡ıË- Î·È Û˘ÁÎÂÎÚÈ̤ӷ ¤¯ÂÈ ‰Âȯı› fiÙÈ ˘¿Ú¯ÂÈ ÈÛ¯˘Ú‹ Û˘- Û˘ ÙˆÓ ÂȤ‰ˆÓ ÙˆÓ ∞£∞ ηıÒ˜ Î·È Ù˘ TSH. Û¯¤ÙÈÛË ÙˆÓ HLA-DR4, DQ8 (DQA1*0301- DQB1*0302) Î·È HLA-DR3, DQ2 (DQA1*0501- ™·Î¯·Ú҉˘ ¢È·‚‹Ù˘ Δ‡Ô˘ 1 DQB1*0201) Î·È ÙÔ˘ ™¢Δ1 ÂÓÒ Ë ·ÚÔ˘Û›· ·Û·Ú- √ ™·Î¯·Ú҉˘ ¢È·‚‹Ù˘ Δ‡Ô˘ 1 (™¢Δ1) Â›Ó·È ÙÔ ÙÈÎÔ‡ ÔͤԘ ÛÙË ı¤ÛË 57 ÙÔ˘ DQB1 Î·È Ù· HLA- ·ÔÙ¤ÏÂÛÌ· ÌÈ·˜ ¯ÚfiÓÈ·˜, ·ÓÔÛÔÏÔÁÈο ÌÂÛÔÏ·‚Ô‡- DR15, DQA1*102-DQB1*0602 ·Ú¤¯Ô˘Ó ÚÔÛÙ·- ÌÂÓ˘, ÊÏÂÁÌÔÓÒ‰Ô˘˜ ‰ÈÂÚÁ·Û›·˜ Ô˘ Ô‰ËÁ› ÛÙ·- Û›· ·fi ÙË ÓfiÛÔ5. ‰È·Î¿ ÛÙËÓ Î·Ù·ÛÙÚÔÊ‹ ÙˆÓ ‚-΢ÙÙ¿ÚˆÓ ÙˆÓ ÓËÛÈ- ∏ ¤Ú¢ӷ Û ‰È·ÁÔÓȉȷο ÔÓÙ›ÎÈ· (NOD) Ô˘ ∞. TÛÈÚÔÁÈ¿ÓÓË 41
·Ó·Ù‡ÛÔ˘Ó ™¢Δ1 ¤‰ˆÛ ÙË ‰˘Ó·ÙfiÙËÙ· Ó· ηٷ- ¿ÏÏ· ÔÚÁ·ÓÔÂȉÈο ‹ ÌË ÔÚÁ·ÓÔÂȉÈο ·˘ÙÔ¿ÓÔÛ· ÓÔ‹ÛÔ˘Ì ÙÔ˘˜ ·ıÔÁÂÓÂÙÈÎÔ‡˜ Ì˯·ÓÈÛÌÔ‡˜ Ô˘ ÓÔÛ‹Ì·Ù·, fiˆ˜ ۷ί·Ú҉˘ ‰È·‚‹Ù˘ Ù‡Ô˘ 1, ·˘- Ô‰ËÁÔ‡Ó ÛÙËÓ Î·Ù·ÛÙÚÔÊ‹ ÙˆÓ ‚-΢ÙÙ¿ÚˆÓ ÙˆÓ ÓË- ÙÔ¿ÓÔÛË ı˘ÚÂÔÂȉ›Ùȉ·, Û. Sjögreen, ÚˆÙÔ·ı‹˜ Ûȉ›ˆÓ ÙÔ˘ ·ÁÎÚ¤·ÙÔ˜ ̤۷ ·fi ÙË Û˘ÓÂÚÁ·Û›· ÙˆÓ ¯ÔÏÈ΋ ΛÚÚˆÛË, ÂÚËÙÔÂȉ‹˜ ‰ÂÚÌ·Ù›Ùȉ·, IgA ·ÓÔ- Ì·ÎÚÔÊ¿ÁˆÓ Î·È ÙˆÓ Δ ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ, ηıÒ˜ Î·È ÙË ÛÔ·Ó¿ÚÎÂÈ·. ∏ ›وÛË Ù˘ ÓfiÛÔ˘ ÛÙÔÓ ÁÂÓÈÎfi ‰Ú¿ÛË ÙˆÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ Ô˘ ÂÎÎÚ›ÓÔÓÙ·È Î·Ù¿ ÙËÓ ÏËı˘ÛÌfi Î˘Ì·›ÓÂÙ·È ·fi 1:300 (¢˘ÙÈ΋ πÚÏ·Ó‰›·) ¤- ÂÓÂÚÁÔÔ›ËÛ‹ ÙÔ˘˜. ŒÙÛÈ, Ù· ·˘ÙÔ·ÓÙÈÁfiÓ· (΢ڛˆ˜ ˆ˜ 1:2000 (μ¢ ∂˘ÚÒË) Ì ·Ó·ÏÔÁ›· 3:1 Á˘Ó·›Î˜/ GAD, IAA, IA-2) Ô˘ ÚÔ·ÙÔ˘Ó ·fi ÙËÓ Â˘Î·ÈÚÈ·- ¿Ó‰Ú˜, ÂÓÒ ‰ÂÓ ÂÚÈÁÚ¿ÊÂÙ·È Û ¿ÙÔÌ· ·ÊÚÈηÓÈ- ΋ ηٷÛÙÚÔÊ‹ ÙˆÓ ‚-΢ÙÙ¿ÚˆÓ ˘Ê›ÛÙ·ÓÙ·È ÂÂÍÂÚ- ΋˜, È·ˆÓÈ΋˜ Î·È ÎÈÓÂ˙È΋˜ ηٷÁˆÁ‹˜. Á·Û›· ·fi Ù· Ì·ÎÚÔÊ¿Á·/‰ÂÓ‰ÚÈÙÈο ·ÙÙ·Ú· Î·È ·- ∏ ·Ó¿ÚÎÂÈ· ÂÓ˙‡ÌˆÓ, ˘Â‡ı˘ÓË ÁÈ· ÙËÓ ·ÙÂÏ‹ ÚÔ˘ÛÈ¿˙ÔÓÙ·È ÛÙ· CD4 ÏÂÌÊÔ·ÙÙ·Ú· Ô˘ Ì ÙË ÛÂÈ- ¤„Ë Ù˘ ÁÏÔ˘Ù¤Ó˘ Î·È ÙËÓ ·Ú·ÁˆÁ‹ ÙÔÍÈÎÒÓ Â- Ú¿ ÙÔ˘˜ ÂÓÂÚÁÔÔÈÔ‡ÓÙ·È Î·È ÂÎÎÚ›ÓÔ˘Ó Î˘ÙÙ·ÚÔΛÓ˜ Ùȉ›ˆÓ, ηıÒ˜ Î·È Ë ·ıÔÏÔÁÈ΋ ÁÏ˘ÎÔ˙˘Ï›ˆÛË ÁÏ˘- fiˆ˜ INF-Á, IFN-·, TNF-‚, IL-2. ∫·ıÒ˜ Ë ‰È·‰Èηۛ· ÎÔÚˆÙÂ˚ÓÒÓ Ô˘ Ô‰ËÁ› Û ·ÓÙ›‰Ú·ÛË ÏÂÎÙ›Ó˘ ÌÂ- ·˘Ù‹ ÂÍÂÏ›ÛÛÂÙ·È, ÚÔ-΢ÙÙ·ÚÔÙÔÍÈο, ÂȉÈο ÁÈ· Ù· ‚- ٷ͇ ÁÏÔ˘Ù¤Ó˘ Î·È Î˘ÙÙ¿ÚˆÓ ÙˆÓ ÂÓÙÂÚÈÎÒÓ Ï·¯ÓÒÓ, ·ÙÙ·Ú·, Δ ÏÂÌÊÔ·ÙÙ·Ú· ‰ÈËıÔ‡Ó Ù· ÓËÛ›‰È· Î·È Î¿- ·ÔÙÂÏÔ‡Ó Ì˯·ÓÈÛÌÔ‡˜ ÚfiÎÏËÛ˘ ‚Ï¿‚˘ ÙÔ˘ Â- Ùˆ ·fi ÙË ‰Ú¿ÛË Ù˘ IL-2 ‰È·ÊÔÚÔÔÈÔ‡ÓÙ·È Û CD8 ÓÙÂÚÈÎÔ‡ ‚ÏÂÓÓÔÁfiÓÔ˘. ¶ÏËıÒÚ· ·ÓÔÛÔÏÔÁÈÎÒÓ, Â- ΢ÙÙ·ÚÔÙÔÍÈο Δ ÏÂÌÊÔ·ÙÙ·Ú·. ∏ INF-Á Ô˘ ·Â- ÚÈ‚·ÏÏÔÓÙÈÎÒÓ (ÂÓÙÂÚÈÎfi˜ ·‰ÂÓÔ˚fi˜ 12), ·ÏÏ¿ ΢ڛˆ˜ Ï¢ıÂÚÒÓÂÙ·È ÙfiÛÔ ·fi Ù· CD4 fiÛÔ Î·È ·fi Ù· ÁÂÓÂÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ Ê·›ÓÂÙ·È fiÙÈ ÂÌϤÎÔÓÙ·È ÛÙËÓ CD8 ÚÔηÏ› ÙËÓ ¤ÎÎÚÈÛË ÛËÌ·ÓÙÈ΋˜ ÔÛfiÙËÙ·˜ ·ÈÙÈÔ·ıÔÁ¤ÓÂÈ· Ù˘ ÓfiÛÔ˘. ΔÔ 90-95% ÙˆÓ ·ÛıÂÓÒÓ IFN-Á, TNF-·, IL-1‚ ηıÒ˜ Î·È ÂÏ¢ı¤ÚˆÓ ÚÈ˙ÒÓ Ì ÎÔÈÏÈÔοÎË ÂÎÊÚ¿˙Ô˘Ó HLA-DQ2 (DQA1*0501/ DQB1*0201 ‹ DRB1*O301) / DQ8 (DQA1*0301 / ∏2√2, ¡√ ·fi Ù· Ì·ÎÚÔÊ¿Á·. ŒÙÛÈ, ÙÔ Û‡ÓÔÏÔ ÙˆÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ Ô˘ ·Ú¿ÁÔÓÙ·È ·fi Ù· Ì·ÎÚÔÊ¿Á· DQB1*0302). ΔÔ ÁÂÁÔÓfi˜ fï˜ fiÙÈ ÙÔ 80 % ÙˆÓ ÌÔ- Î·È Ù· Δ ÏÂÌÊÔ·ÙÙ·Ú· ¿ÁÔ˘Ó ÙËÓ ¤ÎÊÚ·ÛË Fas ÓÔ˙˘ÁˆÙÈÎÒÓ ‰È‰‡ÌˆÓ Î·È ÙÔ 10% ÙˆÓ Û˘ÁÁÂÓÒÓ ·’ ÌÔÚ›ˆÓ ÛÙ· ‚-·ÙÙ·Ú· Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ Î·Ù·- ‚·ıÌÔ‡ ÂΉËÏÒÓÔ˘Ó ÙË ÓfiÛÔ ˘Ô‰ËÏÒÓÂÈ ÙËÓ ‡·Ú- ÛÙÚÔÊ‹ ÙÔ˘˜ ̤ۈ Fas-FasL —·fiÙˆÛË ‹/Î·È Ì¤- ÍË Î·È ¿ÏÏˆÓ ÌË-HLA ÁÔÓȉ›ˆÓ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ۈ ÂÚÊÔÚ›Ó˘/granzyme— ΢ÙÙ·ÚÈ΋ Ó¤ÎÚˆÛË6,7. ÙËÓ ÂȉÂÎÙÈÎfiÙËÙ· ÛÙË ÓfiÛÔ, fiˆ˜ 5q31-q33 ¶ÂÚÈÛÛfiÙÂÚ· ·fi 30 ¯ÚfiÓÈ· ¤¯Ô˘Ó ÂÚ¿ÛÂÈ (CELIAC2) ¯ÚˆÌÔÛˆÌȷΤ˜ ı¤ÛÂȘ fiÔ˘ ‰ڿ˙ÔÓÙ·È ·fi ÙËÓ ÚÒÙË ÂÚÈÁÚ·Ê‹ ÙˆÓ ÂȉÈÎÒÓ ·˘ÙÔ·ÓÙÈÛˆ- ÁÔÓ›‰È· Ô˘ Έ‰ÈÎÔÔÈÔ‡Ó ÙË Û‡ÓıÂÛË Î˘ÙÙ·ÚÔÎÈÓÒÓ, Ì¿ÙˆÓ ¤Ó·ÓÙÈ ÙˆÓ ÓËÛȉ›ˆÓ ÙÔ˘ ·ÁÎÚ¤·ÙÔ˜ (ICA) 2q33 (CELIAC3) ÙˆÓ CD28, CTLA-4 Î·È ICOS ÌÔ- Ô˘ ·ÓÙȉÚÔ‡Ó Ì ÔÈΛϷ ·˘ÙÔ·ÓÙÈÁfiÓ·, Ù· ΢ÚÈfiÙÂ- Ú›ˆÓ ηıÒ˜ Î·È 19p13.1 (CELIAC4)9. Ú· ÙˆÓ ÔÔ›ˆÓ Â›Ó·È Ë ·ÔηڂÔÍ˘Ï¿ÛË ÙÔ˘ ÁÏÔ˘Ù·- Δ· ÎÏÈÓÈο Û˘ÌÙÒÌ·Ù· Ù˘ ÓfiÛÔ˘ ÂÌÊ·Ó›˙ÔÓÙ·È ÌÈÓÈÎÔ‡ ÔͤԘ (GAD), Ë ÂÓ‰ÔÁÂÓ‹˜ ÈÓÛÔ˘Ï›ÓË π∞∞ Î·È ·fi ÙËÓ ·È‰È΋ ËÏÈΛ·, fiÔ˘ Ë ‰˘Û·ÔÚÚfiÊËÛË ¤¯ÂÈ Ë π∞-2 Ù˘ÚÔÛÈÓÈ΋ ʈÛÊ·Ù¿ÛË. ∞ÓÙÈ-GAD ·ÓÙÈÛÒÌ·- ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÂÏ·Ùو̤ÓË „˘¯Ôۈ̷ÙÈ΋ ·Ó¿Ù˘- Ù· ·ÓȯÓ‡ÔÓÙ·È ÛÙÔ 70-85% ÙˆÓ ·ÛıÂÓÒÓ ÂÓÒ ·ÓÙÈ- ÍË, Ú·¯›Ùȉ·, ¢ÂÚÂıÈÛÙfiÙËÙ·, ÏÔÈÌÒÍÂȘ, ˘ÔÏ·Û›· π∞∞ Î·È ·ÓÙÈ-π∞-2 ÛÙÔ 45-59% Î·È 58-75% ·ÓÙ›ÛÙÔȯ·. ·‰·Ì·ÓÙ›Ó˘, ηı˘ÛÙ¤ÚËÛË Ù˘ ÂÊ˂›·˜, ÌÂ Û˘ÓËı¤- ∏ ·ÚÔ˘Û›· ‰‡Ô ‹/Î·È ÙÚÈÒÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ Û ÛÙÂÚË fï˜ ÂΉ‹ÏˆÛË ÙȘ ‰È·ÚÚÔ˚Τ˜ ÎÂÓÒÛÂȘ. ˘ÁÈ‹ ¿ÙÔÌ· Î·È Î˘Ú›ˆ˜ ‰›‰˘Ì· ·‰¤ÏÊÈ· ‹ ÚÒÙÔ˘ ™ÙÔ˘˜ ÂÓ‹ÏÈΘ Ë ÓfiÛÔ˜ ÂΉËÏÒÓÂÙ·È Ì ‹È· ÛȉË- ‚·ıÌÔ‡ Û˘ÁÁÂÓ›˜ ÓÔÛÔ‡ÓÙˆÓ, ¤¯ÂÈ ıÂÙÈ΋ ÚÔÁÓˆ- ÚÔÂÓÈ΋ ·Ó·ÈÌ›·, ·ÊıÒ‰Ë ¤ÏÎË, ‰˘Û„›·, η¯ÂÍ›·, ÛÙÈ΋ ·Í›· ηıÒ˜ ·˘Í¿ÓÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ Ù˘ ÔÛÙÂÔfiÚˆÛË ÂÓÒ Û¿ÓÈ· Ì ÂÓ‰ÔÎÚ·ÓȷΤ˜ ·ÔÙÈ- ÓfiÛÔ˘8. Ù·ÓÒÛÂȘ, ÂÈÏË„›·, ÂÚÈÊÂÚÈ΋ Ó¢ÚÔ¿ıÂÈ·, ηٿ- ıÏÈ„Ë, „‡¯ˆÛË. √È ÎÏÈÓÈΤ˜ ÌÔÚʤ˜ Ù˘ ÓfiÛÔ˘ ÂÚÈ- ∫ÔÈÏÈÔοÎË ÁÚ¿ÊÔÓÙ·È ˆ˜ ·Áfi‚Ô˘ÓÔ, ÛÙËÓ ÎÔÚ˘Ê‹ ÙÔ˘ ÔÔ›Ô˘ ‚Ú›ÛÎÂÙ·È Ë ÎÏ·ÛÈ΋ (Ù˘È΋) ÌÔÚÊ‹ Î·È ·ÎÔÏÔ˘ıÔ‡Ó ∏ ÎÔÈÏÈÔοÎË ‹ Û‡Ó‰ÚÔÌÔ ‰˘Û·ÔÚÚfiÊËÛ˘ Ù˘ Ë ˘ÔÎÏÈÓÈ΋ (¿Ù˘Ë) Î·È Ë ·Û˘Ìو̷ÙÈ΋ ÂÓÒ ÛÙË ÁÏÔ˘Ù¤Ó˘ ‹ ÙÚÔÈÎfi sprue Â›Ó·È Ì›· ·˘ÙÔ¿ÓÔÛË ‚¿ÛË Â‰Ú¿˙ÂÙ·È Ë Ï·Óı¿ÓÔ˘Û· ‹ ‰˘ÓËÙÈ΋ ÎÔÈÏÈÔο- ÊÏÂÁÌÔÓ҉˘ ÓfiÛÔ˜ ÙÔ˘ ÏÂÙÔ‡ ÂÓÙ¤ÚÔ˘, ÔÏ˘·- ÎË10. Δ· ‰È·ÁÓˆÛÙÈο ÎÚÈÙ‹ÚÈ· Ù˘ ÓfiÛÔ˘ ÂÚÈÏ·Ì‚¿- Ú·ÁÔÓÙÈ΋˜ ·ÈÙÈÔÏÔÁ›·˜. ∏ ÎÏÈÓÈ΋ ¤ÎÊÚ·Û‹ Ù˘ Â›Ó·È ÓÔ˘Ó ÙËÓ ÎÏÈÓÈ΋ Û˘Ìو̷ÙÔÏÔÁ›·, ÙÔÓ ıÂÙÈÎfi ·ÓÔ- ÙÔ ·ÔÙ¤ÏÂÛÌ· ÌfiÓÈÌ˘ ‰˘Û·ÓÂÍ›·˜ ÛÙË ÁÏÔ˘Ù¤ÓË, ÛÔÏÔÁÈÎfi ¤ÏÂÁ¯Ô Ì ÙËÓ ·ÚÔ˘Û›· ·˘ÙÔ·ÓÙÈۈ̿وÓ, ÂÓfi˜ ÚˆÙÂ˚ÓÈÎÔ‡ Û˘ÛÙ·ÙÈÎÔ‡ Ô˘ ÂÚȤ¯ÂÙ·È ÛÙÔ ÛÈ- ¤Ó·ÓÙÈ ÁÏÈ·‰›Ó˘ (AGA), ¤Ó·ÓÙÈ ÂÓ‰ÔÌ˘˝Ô˘ (EmA) Î·È Ù¿ÚÈ, ÙË Û›Î·ÏË, ÙÔ ÎÚÈı¿ÚÈ Î·È ÙË ‚ÚÒÌË, Û ¿ÙÔÌ· Ì ¤Ó·ÓÙÈ ÈÛÙÈ΋˜ ÙÚ·ÓÛÁÏÔ˘Ù·ÌÈÓ¿Û˘ (tTG), Î·È ÙË ¯·- ÁÂÓÂÙÈ΋ ÚԉȿıÂÛË. ∏ ÓfiÛÔ˜ Û˘¯Ó¿ Û˘Ó˘¿Ú¯ÂÈ Ì ڷÎÙËÚÈÛÙÈ΋ ÈÛÙÔÏÔÁÈ΋ ÂÈÎfiÓ·, Ì ·ÙÚÔÊ›· ÙˆÓ ıË- 42 √ÚÁ·ÓÔÂȉÈο ·˘ÙÔ¿ÓÔÛ· ÓÔÛ‹Ì·Ù·
ÏÒÓ Î·È ˘ÂÚÏ·Û›· ÙˆÓ ÎÚ˘ÙÒÓ, ÛÙË ‚ÈÔ„›· ÙÔ˘ ÏÂ- Á‹˜. ™‹ÌÂÚ·, Ì ÙËÓ ÂͤÏÈÍË Ù˘ ‚ÈÔÙ¯ÓÔÏÔÁ›·˜, Á›- ÙÔ‡ ÂÓÙ¤ÚÔ˘. ÓÔÓÙ·È ÚÔÛ¿ıÂȘ ÙÚÔÔÔ›ËÛ˘ ÙˆÓ ÛÈÙËÚÒÓ ΔÔ ÌÔÓÙ¤ÏÔ Ô˘ ÚÔÙ›ÓÂÙ·È ÁÈ· ÙËÓ ·ÓÔÛÔ·- (˘‚ÚȉÈÛÌfi˜), ¯ÔÚ‹ÁËÛ˘ ‚·ÎÙËÚÈ·ÎÒÓ ÂÓ‰ÔÂÙȉ·- ıÔÁ¤ÓÂÈ· Ù˘ ÎÔÈÏÈÔο΢ ÂÚÈÏ·Ì‚¿ÓÂÈ ÙË Û˘ÌÌÂÙÔ- ÛÒÓ Î·È ·Ó·ÛÙÔϤˆÓ Ù˘ tTG ηıÒ˜ Î·È Â·ÁˆÁ‹ η- ¯‹ ÙfiÛÔ Ù˘ Ê˘ÛÈ΋˜ fiÛÔ Î·È Ù˘ ›ÎÙËÙ˘ ·ÓÔÛÈ·- Ù·ÛÙÔÏ‹˜ ‹ ·ÓÔ¯‹˜ (·ÓÔ¯ÔÁfiÓ· ‰ÂÓ‰ÚÈÙÈο ·ÙÙ·Ú·) ΋˜ ·¿ÓÙËÛ˘, Ô˘ ÂÓÂÚÁÔÔÈÔ‡ÓÙ·È ·fi ÙËÓ ·-ÁÏÈ·- ÛÙ· Ï·›ÛÈ· ηÙ¢ı˘ÓfiÌÂÓ˘ ÂÎÙÚÔ‹˜ ÙÔ˘ ·ÓÔÛÔ- ‰›ÓË, ÂÙ›‰ÈÔ ÏÔ‡ÛÈÔ Û ÚÔÏ›ÓË Î·È ÁÏÔ˘Ù·Ì›ÓË, ·ıÔÁÂÓÂÙÈÎÔ‡ Ì˯·ÓÈÛÌÔ‡. ·ÓıÂÎÙÈÎfi ÛÙË ÚˆÙÂfiÏ˘ÛË, ÚÔ˚fiÓ Ù˘ ‰È¿Û·Û˘ Ù˘ ÁÏÔ˘Ù¤Ó˘ ·fi ÙȘ ÂÓ‰ÔÂÙȉ¿ÛÂȘ. ™˘ÁÎÂÎÚÈ̤- μÈ‚ÏÈÔÁÚ·Ê›· Ó·, Ë ÈÛÙÈ΋ ÙÚ·ÓÛÁÏÔ˘Ù·ÌÈÓ¿ÛË, ¤Ó˙˘ÌÔ ˘Â‡ı˘ÓÔ ÁÈ· ÙËÓ ·Ó¿Ï·ÛË ÙˆÓ ÈÛÙÒÓ Î·È ÙË Û‡ÓıÂÛË ÎÔÏÏ·- 1. Weetman AP. Autoimmune thyroid disease: propagation and progression. European Journal of Endocrinology ÁfiÓÔ˘, ÚÔηÏ› ··Ì›ÓˆÛË Ù˘ ÁÏÔ˘Ù·Ì›Ó˘ Î·È ¤Î- 2003; 148: 1-9. ÊÚ·ÛË ÓÂÔÂÈÙfiˆÓ, ÛÙËÓ 57-73 ·ÏÏËÏÔ˘¯›· ·ÌÈÓÔ- 2. Catureli P, Kimura H, Rocchi R, et al. Autoimmune thyroid ͤˆÓ, Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÂÓÂÚÁÔÔ›ËÛË Ù˘ Δh1 ·- diseases. Curr Opin Rheumatol 2007; 19: 44-8. ÓÔÛȷ΋˜ ·¿ÓÙËÛ˘ Ì ·Ú·ÁˆÁ‹ IFN-Á Î·È TNF-· 3. Jacobson EM, Huber A, Tomer Y. The HLA gene complex Ô˘ Ô‰ËÁ› Û ·ÙÚÔÊ›· ÙˆÓ ıËÏÒÓ Î·È ˘ÂÚÏ·Û›· in thyroid autoimmunity: from epidemiology to etiology. ÙˆÓ ÎÚ˘ÙÒÓ ·ÓÙ›ÛÙÔȯ· Î·È Ù˘ Δh2 ·ÓÔÛȷ΋˜ ·¿- J Autoimmunity 2008; 30(1-2): 58-62. ÓÙËÛ˘ fiÔ˘ Ë ¤ÎÎÚÈÛË IL-4,5,6,10 Î·È TGF-‚ ¿ÁÂÈ 4. Tomer Y, Huber A. The etiology of autoimmune thyroid ÙËÓ ·Ú·ÁˆÁ‹ ·ÓÙÈۈ̿وÓ. ¶·Ú¿ÏÏËÏ· Ë 31-43 ·Ï- disease: A story of genes and environment. Article in press. J Autoimmunity 2009; 1-9. ÏËÏÔ˘¯›· ·ÌÈÓÔͤˆÓ ¿ÁÂÈ ÙËÓ ¤ÎÎÚÈÛË IL-15 Ô˘ 5. Knip M, Siljander H. Autoimmune mechanism in Type 1 Ô‰ËÁ› Û ¤ÎÊÚ·ÛË MICA ÛÙ· ÂÈıËÏȷο ÂÓÙÂÚÔ·Ù- diabetes. Autoimmun Rev. 2008; 7(7): 550-7. Ù·Ú· Î·È NKG2D ˘Ô‰Ô¯¤· ÛÙ· ÂÓ‰ÔÂÈıËÏȷο 6. Ji-Won Yoon Hee-Sook Jun. Cellular and Molecular Patho- ÏÂÌÊÔ·ÙÙ·Ú·, Ë Û‡Ó‰ÂÛË ÙˆÓ ÔÔ›ˆÓ ¤¯ÂÈ ˆ˜ ·Ô- genic Mechanisms of Insulin-Dependent Diabetes Melli- Ù¤ÏÂÛÌ· ÙËÓ Î·Ù·ÛÙÚÔÊ‹ ÙˆÓ ÂÓÙÂÚÔ΢ÙÙ¿ÚˆÓ11. tus. Ann NY Acad Sci. 2001; 928: 200-11. ∏ Ï‹Ú˘ ·fiÛ˘ÚÛË Ù˘ ÁÏÔ˘Ù¤Ó˘ ·fi ÙÔ ‰È- 7. Yoon JW, Jyn HS. Autoimmune destruction of pancreatic ·ÈÙÔÏfiÁÈÔ ÙÔ˘ ·ÛıÂÓÔ‡˜ Â›Ó·È Ô˘ÛÈ·ÛÙÈο Ë ÌÔÓ·‰È΋ beta cells. Am J Ther. 2005; 12(6): 580-91. ıÂڷ¢ÙÈ΋ ÚÔÛ¤ÁÁÈÛË Ù˘ ÓfiÛÔ˘. ∫ÏÈÓÈ΋ ‚ÂÏÙ›ˆ- 8. Taplin CE, Barker JM. Autoantibodies in type 1 diabetes. Au- ÛË ÂÌÊ·Ó›˙ÂÙ·È Ôχ Û‡ÓÙÔÌ· ÌÂÙ¿ ÙË ‰›·ÈÙ·, ÂÓÒ Ë toimmunity 2008; 41(1): 11-8. ·ÚÓËÙÈÎÔÔ›ËÛË ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ Î·È Ë Â·Ó·- 9. Koning F, Gilissen L, Wijmenga C. Gluten: a two-edged sword. Immunopathogenesis of celiac disease. Springer ÊÔÚ¿ Ù˘ ·Ú¯ÈÙÂÎÙÔÓÈ΋˜ ÙÔ˘ ÂÓÙÂÚÈÎÔ‡ ‚ÏÂÓÓÔÁfiÓÔ˘ Semin Immun 2005; 27: 217-232. ·Ó·Ì¤ÓÂÙ·È ÂÚ›Ô˘ ÌÂÙ¿ ·fi ¤Ó·Ó ¯ÚfiÓÔ. ∏ ÌË 10. Leeds JS, Hopper AD, Sanders DS. Coeliac disease. British ·ÓÙ·fiÎÚÈÛË ÛÙË ‰›·ÈÙ· ··ÈÙ› ‰È·ÊÔÚԉȿÁÓˆÛË ‹ Medical Bulletin 2008; 88: 157-170. ı¤ÙÂÈ ÙÔ ÂӉ¯fiÌÂÓÔ Ù˘ ·ÓıÂÎÙÈ΋˜ ÓfiÛÔ˘, Ë ·ÓÙÈÌÂ- 11. Dewar D, Pereira SP, Ciclitira PJ. The pathogenesis of ÙÒÈÛË Ù˘ ÔÔ›·˜ ¯Ú‹˙ÂÈ ·ÓÔÛÔηٷÛÙ·ÏÙÈ΋˜ ·Áˆ- coeliac disease. Int J Biochem Cell Biol. 2004; 36: 17-24. ∞˘ÙÔ¿ÓÔÛ· ÓÔÛ‹Ì·Ù·
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2009; 1: 43 – 48
Δ· ·˘ÙÔ¿ÓÔÛ· ÚÂ˘Ì·ÙÈο ÓÔÛ‹Ì·Ù· (∞ƒ¡) ‹ ·˘ÙÔ¿- ÙËÓ ÂÓÂÚÁfiÙËÙ· Ù˘ ÓfiÛÔ˘ (c-ANCA, anti-Nucleo- ÓÔÛ· Û˘ÛÙËÌ·ÙÈο ÓÔÛ‹Ì·Ù· ÚÔÛ‚¿ÏÏÔ˘Ó ÂÚ›Ô˘ some) Î·È ‰) ·Ú¤¯ÂÈ ¯Ú‹ÛÈ̘ ÚÔÁÓˆÛÙÈΤ˜ ÏË- ÙÔ 3-5% ÙÔ˘ ÁÂÓÈÎÔ‡ ÏËı˘ÛÌÔ‡ Î·È Ë ÎÏÈÓÈ΋ ÙÔ˘˜ ÚÔÊÔڛ˜. Δ· ΢ÚÈfiÙÂÚ· ·˘ÙÔ·ÓÙÈÛÒÌ·Ù· Ô˘ ¯ÚË- ‰È·‰ÚÔÌ‹ ÔÈΛÏÏÂÈ, ·fi Ôχ ‹È· ¤ˆ˜ Ôχ ‚·ÚÈ¿ ÛÈÌÔÔÈÔ‡ÓÙ·È Û˘Ó‹ıˆ˜ ÛÙËÓ ÎÏÈÓÈ΋ Ú·ÎÙÈ΋ ÁÈ· ÙË Ì ÚÔÛ‚ÔÏ‹ ˙ˆÙÈÎÒÓ ÔÚÁ¿ÓˆÓ (ÓÂÊÚÔ›, Ó‡ÌÔÓ˜, ‰È¿ÁÓˆÛË ÙˆÓ ∞ƒ¡ ·Ó·Ê¤ÚÔÓÙ·È ÛÙË Û˘Ó¤¯ÂÈ·. ÎÂÓÙÚÈÎfi Ó¢ÚÈÎfi Û‡ÛÙËÌ·). Δ· ·›ÙÈ· Ô˘ ÚÔηÏÔ‡Ó Ù· ∞ƒ¡ ‰ÂÓ ¤¯Ô˘Ó ·ÎfiÌË ‰È¢ÎÚÈÓÈÛı›, ·Ó Î·È ¤¯Ô˘Ó ∞ÓÙÈ˘ÚËÓÈο ·ÓÙÈÛÒÌ·Ù· (anti-nuclear ·Ó·Ù˘¯ı› ‰È¿ÊÔÚ˜ ıˆڛ˜ Ô˘ ÚÔÛ·ıÔ‡Ó Ó· antibodies, ANA) ÂÍËÁ‹ÛÔ˘Ó ÙÔ Ê·ÈÓfiÌÂÓÔ ·˘Ùfi. ∂›Ó·È fï˜ ÁÂÓÈο ·- ∏ ·ÚÔ˘Û›· ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ÛÙÔÓ ÔÚfi ÙˆÓ ·ÛıÂ- Ú·‰ÂÎÙfi fiÙÈ ÔÏÏÔ› ·Ú¿ÁÔÓÙ˜ fiˆ˜ ÁÂÓÂÙÈÎÔ›, Â- ÓÒÓ, Ô˘ ·ÓÙȉÚÔ‡Û·Ó Ì ˘ÚËÓÈο Û˘ÛÙ·ÙÈο, ¤ÁÈÓ ÚÈ‚·ÏÏÔÓÙÈÎÔ›, ÔÚÌÔÓÈÎÔ› Î·È „˘¯ÔÏÔÁÈÎÔ› Û˘Ì‚¿Ï- ÁÓˆÛÙ‹ ÙÔ 1948 fiÙ·Ó Ô Hargraves Î·È Û˘Ó.2 ·Ú·Ù‹- ÏÔ˘Ó ÛÙËÓ ÂÌÊ¿ÓÈÛ‹ ÙÔ˘˜. ÚËÛ·Ó fiÙÈ Ô ÔÚfi˜ ÙˆÓ ·ÛıÂÓÒÓ ÌÂ Û˘ÛÙËÌ·ÙÈÎfi ÂÚ˘- Δ· ∞ƒ¡ ¯·Ú·ÎÙËÚ›˙ÔÓÙ·È ·fi ‰È¿Û·ÛË ÙÔ˘ ıËÌ·ÙÒ‰Ë Ï‡ÎÔ (™∂§), ˆ·˙fiÌÂÓÔ˜ Ì ˘Ú‹Ó˜ Ì˯·ÓÈÛÌÔ‡ Ù˘ ·ÓÔÛȷ΋˜ ·ÓÔ¯‹˜, ‰ËÌÈÔ˘ÚÁ›· ·˘- ΢ÙÙ¿ÚˆÓ, ‰ËÌÈÔ˘ÚÁÔ‡Û ·ÓÔÛÔÛ˘ÌϤÁÌ·Ù· Ô˘ ÙÔ‰Ú·ÛÙÈÎÒÓ μ (·˘ÙÔ·ÓÙÈÛÒÌ·Ù·) Î·È Δ-ÏÂÌÊÔ΢ÙÙ¿- Ê·ÁÔ΢ÙÙ·ÚÒÓÔÓÙ·Ó ·ÚÔ˘Û›· Û˘ÌÏËÚÒÌ·ÙÔ˜ ·fi ÚˆÓ, Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·˘ÙÔ¿ÓÔÛË ·¿ÓÙËÛË, Ô˘ ˙ÒÓÙ· ÔÏ˘ÌÔÚÊÔ‡ÚËÓ· (Le Ê·ÈÓfiÌÂÓÔ). Δ· Ê·ÁÔ- Ô‰ËÁ› Û ¯ÚfiÓÈ· ÊÏÂÁÌÔÓ‹ Î·È ÈÛÙÈ΋ ‚Ï¿‚Ë. Δ· ·˘- ΢Ùٷڈ̤ӷ ·ÓÔÛÔÛ˘ÌϤÁÌ·Ù· ÂÌÊ·Ó›˙ÔÓÙ·Ó ˆ˜ ÙÔ·ÓÙÈÛÒÌ·Ù· ·ÔÙÂÏÔ‡Ó Û˘¯Ófi ‡ÚËÌ· ÛÙÔÓ ÔÚfi ÌÈ· ‚·ÛÂfiÊÈÏË Ì¿˙· ̤۷ ÛÙÔ Î˘ÙÙ·ÚfiÏ·ÛÌ· ÙˆÓ 1 ÙˆÓ ·ÛıÂÓÒÓ Ì ∞ƒ¡ . ™Ùfi¯ÔÈ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ÔÏ˘ÌÔÚÊÔ˘Ú‹ÓˆÓ, Ô˘ ÔÓÔÌ¿ÛıËÎ·Ó Î‡ÙÙ·Ú· χ- Â›Ó·È ‰È¿ÊÔÚ· ÛÙÔȯ›· ÙÔ˘ ˘Ú‹Ó· Î·È ÙÔ˘ ΢ÙÙ·ÚÔ- ÎÔ˘ (Le cells). Ï¿ÛÌ·ÙÔ˜ ÙˆÓ Î˘ÙÙ¿ÚˆÓ (΢ڛˆ˜ ÚˆÙ½Ó˜ Û ÚÈ- ™ËÌ·ÓÙÈÎfi ÛÙ·ıÌfi ÛÙË ÌÂϤÙË ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆ- ‚ÔÓÔ˘ÎÏÂÔÚˆÙÂ˚ÓÈο Û‡ÌÏÔη ‹ ÂχıÂÚ˜). ∏ ·- Ì¿ÙˆÓ ·ÔÙ¤ÏÂÛÂ Ë ÂÊ·ÚÌÔÁ‹ ÙÔ˘ ¤ÌÌÂÛÔ˘ ·ÓÔÛÔ- Ó›¯Ó¢ÛË Î·È Ë Ù·˘ÙÔÔ›ËÛË Ù˘ ÂȉÈÎfiÙËÙ·˜ ÙˆÓ ·˘- ÊıÔÚÈÛÌÔ‡ (indirect immunofluorescence, IIF) ÁÈ· ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ·ÔÙÂÏ› ¯Ú‹ÛÈÌÔ ÂÚÁ·ÏÂ›Ô ÛÙË ‰È·- ÚÒÙË ÊÔÚ¿ ·fi ÙÔÓ Friou3 Ô˘ Ô‰‹ÁËÛ ÛÙËÓ ÁÓˆÛÙÈ΋ ÚÔÛ¤ÁÁÈÛË ÙˆÓ ∞ƒ¡ ‰ÈfiÙÈ: ·) ÂȂ‚·ÈÒÓÂÈ ·Ó·ÁÓÒÚÈÛË Ó¤ˆÓ ΢ÎÏÔÊÔÚÔ‡ÓÙˆÓ ·ÓÙÈۈ̿وÓ, ÙË ‰È¿ÁÓˆÛË Î·È Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ Î·Ù¿Ù·ÍË Ù˘ ÓfiÛÔ˘ ÙÔÓ ÚÔÛ‰ÈÔÚÈÛÌfi ÙˆÓ Î˘ÙÙ·ÚÈÎÒÓ ·ÓÙÈÁfiÓˆÓ ÛÙfi- (dsDNA, Sm), ‚) Û˘Óԉ‡ÂÈ ÎÏÈÓÈο ¯·Ú·ÎÙËÚÈÛÙÈο ¯ˆÓ ηıÒ˜ Î·È ÙË Û¯¤ÛË ÙÔ˘˜ Ì ٷ ÎÏÈÓÈο Û‡Ó- ÁÓˆÚ›ÛÌ·Ù· Ù˘ ÓfiÛÔ˘ (Scl-70, Jo-1), Á) Û¯ÂÙ›˙ÂÙ·È Ì ‰ÚÔÌ·. ΔÔ ÁÂÁÔÓfi˜ fiÙÈ Ù· ·ÓÙÈÛÒÌ·Ù· Ô˘ ·ÓȯÓ‡- 44 ∂ÚÁ·ÛÙËÚȷ΋ ÚÔÛ¤ÁÁÈÛË ·˘ÙÔ¿ÓÔÛˆÓ ÚÂ˘Ì·ÙÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ
ıËÎ·Ó Ì ÙË ‰ÔÎÈÌ·Û›· ÙˆÓ Le ΢ÙÙ¿ÚˆÓ ·ÏÏ¿ Î·È Ì ٷ ·ÏÏ¿ Î·È Û ÏÔÈÌÒ‰Ë [™∂§, ÚÂ˘Ì·ÙÔÂȉ‹ ·ÚıÚ›ÙÈ- ¿ÏϘ ‰ÔÎÈ̷ۛ˜ Ô˘ ·ÎÔÏÔ‡ıËÛ·Ó, ÛÙÚ¤ÊÔÓÙ·È ‰· (ƒA), Ê·Ú̷΢ÙÈÎfi χÎÔ, ¯ÚfiÓÈ· ÂÓÂÚÁfi Ë·Ù›ÙÈ- ¤Ó·ÓÙÈ Û˘ÛÙ·ÙÈÎÒÓ ÙÔ˘ ˘Ú‹Ó·, ›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ‰·, ÏÔÈÌÒ‰Ë ÌÔÓÔ˘Ú‹ÓˆÛË]. ∞ÓÙ›ıÂÙ·, ·ÓÙÈÛÒÌ·Ù· ÙË ‰ÈÂıÓ‹ ηıȤڈÛË ÙÔ˘ fiÚÔ˘ ·ÓÙÈ˘ÚËÓÈο ·ÓÙÈ- ¤Ó·ÓÙÈ ÂÈÙfiˆÓ ÙÔ˘ ‰ÈÏ‹˜ ¤ÏÈη˜ ds-DNA ¤¯Ô˘Ó ÛÒÌ·Ù· (Anti Nuclear Antibodies, ANA). ™‹ÌÂÚ· Ô ÛËÌ·ÓÙÈ΋ Û˘Û¯¤ÙÈÛË Ì ÙÔÓ ™∂§ Î·È ıˆÚÔ‡ÓÙ·È ÂÈ- fiÚÔ˜ ∞¡∞ ¯ÚËÛÈÌÔÔÈÂ›Ù·È ÛÙË ‰È·ÁÓˆÛÙÈ΋ Ú·- ‰ÈÎfi˜ ‰È·ÁÓˆÛÙÈÎfi˜ ‰Â›ÎÙ˘ Ù˘ ÓfiÛÔ˘1. Δ· ·ÓÙÈÛÒ- ÎÙÈ΋ Ì ¢ڇÙÂÚË ¤ÓÓÔÈ· Î·È ÂÚÈÏ·Ì‚¿ÓÂÈ ·ÓÙÈÛÒ- Ì·Ù· ¤Ó·ÓÙÈ ds-DNA Û¯ÂÙ›˙ÔÓÙ·È Ì ÙËÓ ·ıÔÁ¤ÓÂÈ· Ì·Ù· ¤Ó·ÓÙÈ ˘ÚËÓÈÎÒÓ ·ÏÏ¿ Î·È Î˘ÙÙ·ÚÔÏ·ÛÌ·ÙÈ- Ù˘ ÈÛÙÈ΋˜ ‚Ï¿‚˘ Î·È ÙËÓ ÂÓÂÚÁfiÙËÙ· Ù˘ ÓfiÛÔ˘ ÛÙÔ ÎÒÓ ·ÓÙÈÁfiÓˆÓ. ™∂§, ·ÓȯÓ‡ÔÓÙ·È ÛÙÔ 60-70 % ÙˆÓ ·ÛıÂÓÒÓ Î·È ıÂ- ∏ ·Ú¯È΋ ̤ıÔ‰Ô˜ ·Ó›¯Ó¢Û˘ ÙˆÓ ∞¡∞ Â›Ó·È Ô ˆÚÔ‡ÓÙ·È ‰Â›ÎÙ˜ ‰Ú·ÛÙËÚÈfiÙËÙ·˜ Ù˘ ÓfiÛÔ˘, ΢ڛˆ˜ ¤ÌÌÂÛÔ˜ ·ÓÔÛÔÊıÔÚÈÛÌfi˜, Ô˘ ·ÔÙÂÏ› ‚·ÛÈ΋ Ù˘ ‡·Ú͢ ÓÂÊÚÈ΋˜ Û˘ÌÌÂÙÔ¯‹˜7. ∏ Ú·ÎÙÈ΋ ÂͤٷÛË ÚÔ˘Ù›Ó·˜ (screening test) ÁÈ· οı ¿ÚÚˆÛÙÔ ¯ÚËÛÈÌfiÙËÙ· ÙÔ˘ ÚÔÛ‰ÈÔÚÈÛÌÔ‡ ÙˆÓ ·ÓÙÈ-DNA ·- Ì ˘fiÓÔÈ· ∞ƒ¡. μ·ÛÈÎfi ÏÂÔÓ¤ÎÙËÌ· ÙÔ˘ ÂÌ̤ÛÔ˘ ÓÙÈÛˆÌ¿ÙˆÓ Â›¯Â ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·Ó¿Ù˘ÍË ÔÏ- ·ÓÔÛÔÊıÔÚÈÛÌÔ‡ Â›Ó·È fiÙÈ ·ÓȯÓ‡ÂÈ ·ÓÙÈÛÒÌ·Ù· Ô˘ ÏÒÓ Ù¯ÓÈÎÒÓ. μ·ÛÈ΋ ÚÔ¸fiıÂÛË ÁÈ· ÙËÓ ·ÎÚ›‚ÂÈ· ηχÙÔ˘Ó ¤Ó· ÌÂÁ¿ÏÔ Ê¿ÛÌ· ·ÓÙÈÁfiÓˆÓ ÙÔ˘ ˘Ú‹Ó· Î·È ÙËÓ ÂȉÈÎfiÙËÙ· Ù˘ ÌÂıfi‰Ô˘ Â›Ó·È Ó· ¯ÚËÛÈÌÔÔÈ- 4,5 Î·È ÙÔ˘ ΢ÙÙ·ÚÔÏ¿ÛÌ·ÙÔ˜ . ∏ ̤ıÔ‰Ô˜ Â›Ó·È ·Ï‹, › ·ÔÎÏÂÈÛÙÈο Î·È ÌfiÓÔ ·ÓÙÈÁfiÓÔ ds-DNA Î·È Ó· ¤¯ÂÈ Î·Ï‹ ÂȉÈÎfiÙËÙ· Î·È ÁÈ· ÙËÓ ÂÊ·ÚÌÔÁ‹ Ù˘ Â›Ó·È ÌËÓ ˘¿Ú¯ÂÈ ÚfiÛÌÈÍË Ì ss-DNA, Ù· ·ÓÙÈÛÒÌ·Ù· ··Ú·›ÙËÙ· ˘ÔÛÙÚÒÌ·Ù· ÂÈıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ ÙÔ˘ ÔÔ›Ô˘ ‰ÂÓ Â›Ó·È ÂȉÈο ÁÈ· ÙÔ ™∂§ ·ÏÏ¿ ··- Hep2, IgG ·ÓÙÈÔÚfi˜ ÛËÌ·Ṳ̂ÓÔ˜ Ì ÊıÔÚÈfi¯ÚˆÌ· ÓÙÔ‡Ó Û ‰È¿ÊÔÚ· ÓÔÛ‹Ì·Ù·. Î·È ÌÈÎÚÔÛÎfiÈÔ ÊıÔÚÈÛÌÔ‡. ∞ÚÓËÙÈÎfi ¯·Ú·ÎÙËÚ›˙Â- √È Ï¤ÔÓ ‰È·‰Â‰Ô̤Ó˜ ̤ıÔ‰ÔÈ ÚÔÛ‰ÈÔÚÈ- Ù·È ÙÔ ·ÔÙ¤ÏÂÛÌ· fiÙ·Ó ÛÙ· ·ÙÙ·Ú· ‰ÂÓ ·Ú·ÙËÚ›- ÛÌÔ‡ ·ÓÙÈ-dsDNA ·ÓÙÈÛˆÌ¿ÙˆÓ Â›Ó·È: Ë RIA ˘ÁÚ‹˜ Ù·È ÊıÔÚÈÛÌfi˜, ÂÓÒ ıÂÙÈÎfi ¯·Ú·ÎÙËÚ›˙ÂÙ·È ÙÔ ·ÔÙ¤- Ê¿Û˘ (Farr assay) Ô˘ ıˆÚÂ›Ù·È Ì¤ıÔ‰Ô˜ ·Ó·ÊÔ- ÏÂÛÌ· fiÙ·Ó ÔÈ ˘Ú‹Ó˜ ÙˆÓ Î˘ÙÙ¿ÚˆÓ ‰›ÓÔ˘Ó Ú¿ÛÈ- Ú¿˜, Ô ¤ÌÌÂÛÔ˜ ·ÓÔÛÔÊıÔÚÈÛÌfi˜ (Crithidia luciliae) ÓÔ ÊıÔÚÈÛÌfi. ™ÙÔ ıÂÙÈÎfi ·ÔÙ¤ÏÂÛÌ· ı· Ú¤ÂÈ Ó· Ô˘ Â›Ó·È ÂȉÈ΋ ·ÏÏ¿ fi¯È Ôχ ¢·›ÛıËÙË Ì¤ıÔ‰Ô˜ ÚÔÛ‰ÈÔÚ›˙ÂÙ·È Ô Ù›ÙÏÔ˜, ‰ËÏ·‰‹ Ë ÌÂÁ·Ï‡ÙÂÚË ·Ú·›- Î·È Ë ·ÓÔÛÔÂÓ˙˘ÌÈ΋ ̤ıÔ‰Ô˜ (ELISA), Ë ÔÔ›· ¤¯ÂÈ ˆÛË ÙÔ˘ ÔÚÔ‡ ÙÔ˘ ·ÛıÂÓÔ‡˜ Ô˘ ‰›ÓÂÈ ıÂÙÈÎfi ·Ô- ÌÂÁ¿ÏË Â˘·ÈÛıËÛ›·, ÚÔÛ‰ÈÔÚ›˙ÂÈ Ì ·ÎÚ›‚ÂÈ· fiϘ Ù¤ÏÂÛÌ· Î·È Ó· ·Ó·ÁÓˆÚ›˙ÂÙ·È ÙÔ Â›‰Ô˜ ÙÔ˘ ÊıÔÚÈ- ÙȘ Ù¿ÍÂȘ ÙˆÓ ·ÓÙÈ-dsDNA ·ÓÙÈۈ̿وÓ, ·ÓȯÓ‡ÂÈ ÛÌÔ‡. ™‹ÌÂÚ· Ù· ÂÚÈÛÛfiÙÂÚ· ÂÚÁ·ÛÙ‹ÚÈ· ¯ÚËÛÈÌÔ- fï˜ Î·È ¯·ÌËÏ‹˜ Û˘ÁÁ¤ÓÂÈ·˜ (low avidity) ·ÓÙÈÛÒ- ÔÈÔ‡Ó ˆ˜ Ù›ÙÏÔ ·Ó·ÊÔÚ¿˜ ÙËÓ ·Ú·›ˆÛË 1:160 Ô˘ Ì·Ù· Ì Èı·Ó¤˜ ‰È·ÛÙ·˘ÚÔ‡ÌÂÓ˜ ·ÓÙȉڿÛÂȘ. ÂÍ·ÛÊ·Ï›˙ÂÈ ÂȉÈÎfiÙËÙ· ÂÚ›Ô˘ 90% ÁÈ· ÙË ‰È¿ÁÓˆÛË ÙˆÓ ∞ƒ¡6. ™Â ¤Ó· ıÂÙÈÎfi ·ÔÙ¤ÏÂÛÌ· ‰È·ÎÚ›ÓÔÓÙ·È ‰È¿ÊÔÚÔÈ Ù‡ÔÈ ÊıÔÚÈÛÌÔ‡ Î·È ·˘Ùfi ÂÍ·ÚÙ¿Ù·È ·fi Ù· ∞ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÓÔ˘ÎÏÂÔÛÒÌ·ÙÔ˜ ·ÓÙÈÁfiÓ· ¤Ó·ÓÙÈ ÙˆÓ ÔÔ›ˆÓ ηÙ¢ı‡ÓÔÓÙ·È Ù· ∞¡∞. ΔÔ ÓÔ˘ÎÏÂfiۈ̷ Â›Ó·È Ë ‚·ÛÈ΋ ‰ÔÌÈ΋ ÌÔÓ¿‰· Ù˘ √È Û˘ÓËı¤ÛÙÂÚÔÈ Ù‡ÔÈ ÊıÔÚÈÛÌÔ‡ ›ӷÈ: Ô ÔÌÔÈÔÁÂ- ¯ÚˆÌ·Ù›Ó˘. ∞ÔÙÂÏÂ›Ù·È ·fi ˙‡ÁË ÙˆÓ 4 ˘ÚËÓÈÎÒÓ Ó‹˜ (DNA, ÈÛÙfiÓ˜), Ô ÂÚÈÊÂÚÈÎfi˜ (ds-DNA, lamins), ÈÛÙÔÓÒÓ ∏2∞, ∏2μ, ∏3 Î·È ∏4 Ô˘ Û¯ËÌ·Ù›˙Ô˘Ó ÙÔ Ô ÛÙÈÎÙfi˜ (nRNP, Sm, Ro, La), Ô ˘ÚËÓÈÛÎÈÎfi˜ (RNA ÔÎÙ·ÌÂÚ¤˜ ÙˆÓ ÈÛÙÔÓÒÓ, Á‡Úˆ ·fi ÙÔ ÔÔ›Ô ÂÚÈÂ- ˘ÚËÓȉ›Ô˘), Ô ÎÂÓÙÚÔÌÂÚȉȷÎfi˜ (ÎÂÓÙÚÔÌÂÚ›‰ÈÔ) Î·È Ï›ÛÛÔÓÙ·È ‰‡Ô ÊÔÚ¤˜ 146 ˙‡ÁË ‚¿ÛÂˆÓ DNA8. Δ· Ô Î˘ÙÙ·ÚÔÏ·ÛÌ·ÙÈÎfi˜ Ô˘ Â›Ó·È ·Ó¿ÏÔÁÔ˜ ÙˆÓ Î˘ÙÙ·- ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙÔ˘ ÓÔ˘ÎÏÂÔÛÒÌ·ÙÔ˜ ·Ó·ÁÓˆÚ›- ÚÈÎÒÓ ÔÚÁ·ÓÈÏ›ˆÓ (ÌÈÙÔ¯fiÓ‰ÚÈ·, ÚÈ‚ÔÛÒÌ·Ù·) ‹ ÙˆÓ ˙Ô˘Ó ÔÏÏ·ÏÔ‡˜ ÂÈÙfiÔ˘˜ Ô˘ Â›Ó·È Î˘Ú›ˆ˜ ›ÙÔ- ÛÙÔȯ›ˆÓ ÙÔ˘ ΢ÙÙ·ÚÔÛÎÂÏÂÙÔ‡, Ô˘ ÙÔÓ ÚÔηÏÔ‡Ó ÔÈ ‰È·ÌfiÚʈÛ˘. ™Ù· ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙÔ˘ ÓÔ˘- (Û˘Û΢‹ Golgi, ·ÎÙ›ÓË, ‚ÈÌÂÓÙ›ÓË). ÎÏÂÔÛÒÌ·ÙÔ˜ ·Ô‰›‰ÂÙ·È Ë ·ÈÙÈÔ·ıÔÁ¤ÓÂÈ· ÙÔ˘ ™∂§. ¶Èı·ÓÒ˜ Û˘ÌϤÁÌ·Ù· ÓÔ˘ÎÏÂÔÛÒÌ·ÙÔ˜ Î·È ·ÓÙÈÛˆ- ∞ÓÙÈ-dsDNA ·ÓÙÈÛÒÌ·Ù· Ì¿ÙˆÓ ¤Ó·ÓÙÈ ·˘ÙÔ‡ ÂÓ·ÔÙ›ıÂÓÙ·È ÛÙË ‚·ÛÈ΋ ÌÂÌ- ΔÔ ÌfiÚÈÔ ÙÔ˘ DNA ‰È·ı¤ÙÂÈ ÔÏÏÔ‡˜ ÂÈÙfiÔ˘˜ ÁÈ’ ‚Ú¿ÓË ÙÔ˘ ÛÂÈÚ¿Ì·ÙÔ˜ Ì ·ÎfiÏÔ˘ıÔ ÙËÓ ÂÓÂÚÁÔ- ·˘Ùfi Î·È Ù· ·ÓÙÈ-DNA ·ÓÙÈÛÒÌ·Ù· ·ÔÙÂÏÔ‡Ó ÂÙÂÚÔ- Ô›ËÛË ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜. ŒÓ·˜ ¿ÏÏÔ˜ Ì˯·ÓÈÛÌfi˜ ÁÂÓ‹ ÔÌ¿‰· ·ÓÙÈÛˆÌ¿ÙˆÓ Ì ÔÏϤ˜ ÂȉÈÎfiÙËÙ˜ (ds- Â›Ó·È Ô in situ Û¯ËÌ·ÙÈÛÌfi˜ ·ÓÔÛÔÛ˘ÌÏÂÁÌ¿ÙˆÓ ÛÙÔ DNA, ss-DNA, ds-DNA Î·È ss-DNA). Δ· ÈÔ Û˘¯Ó¿ ÌÂÛÛ¿ÁÁÂÈÔ. Δ· ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙÔ˘ ÓÔ˘ÎÏÂÔÛÒÌ·- ·ÓÙÈ-DNA ·ÓÙÈÛÒÌ·Ù· Â›Ó·È ·˘Ù¿ ¤Ó·ÓÙÈ ·ÓÙÈÁÔÓÈÎÒÓ ÙÔ˜ ·ÓȯÓ‡ÔÓÙ·È ÛÙÔ 88% ÙˆÓ ·ÛıÂÓÒÓ Ì ™∂§ Î·È Ë Î·ıÔÚÈÛÙÒÓ ÛÙÔ ÌÔÓ‹˜ ¤ÏÈη˜ ss-DNA. Δ· ·ÓÙÈÛÒ- ·Ó¿Ù˘Í‹ ÙÔ˘˜ ÚÔËÁÂ›Ù·È ÙÔ˘ Û¯ËÌ·ÙÈÛÌÔ‡ ÙˆÓ ·ÓÙÈ- Ì·Ù· ·˘Ù¿ ··ÓÙÒÓÙ·È Û ÔÏÏ¿ ÚÂ˘Ì·ÙÈο ÓÔÛ‹Ì·- dsDNA Î·È ·ÓÙÈ-ÈÛÙÔÓÈÎÒÓ ·ÓÙÈۈ̿وÓ. A. ¶·˘Ï›ÙÔ˘-ΔÛÈfiÓÙÛË 45
∞ÓÙÈÎÂÓÙÚÔÌÂÚȉȷο ·ÓÙÈÛÒÌ·Ù· ÏË Ù¯ÓÈ΋. ∂¿Ó Ù· ANA Â›Ó·È ıÂÙÈο ÂÂȉ‹ ÔÈ Ù‡ÔÈ ÙÔ˘ ÊıÔÚÈÛÌÔ‡ ‰ÂÓ Â›Ó·È ÂȉÈÎÔ› ÁÈ· ÙÔ ·Óٛۈ̷ Δ· ·ÓÙÈÎÂÓÙÚÔÌÂÚȉȷο ·ÓÙÈÛÒÌ·Ù· ÛÙÚ¤ÊÔÓÙ·È (ÏËÓ ÙˆÓ ACA), Ô‡Ù ‰È·ÁÓˆÛÙÈÎÔ› ÁÈ· ÙË ÓfiÛÔ, ı· ¤Ó·ÓÙÈ Û˘ÛÙ·ÙÈÎÒÓ ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜ Ù˘ ÌÈÙˆÙÈ΋˜ Ú¤ÂÈ Ó· ÚÔÛ‰ÈÔÚÈÛı› Ë ÂȉÈÎfiÙËÙ·· ÙÔ˘ ·ÓÙÈÛÒ- ·ÙÚ¿ÎÙÔ˘ Ô˘ ÚÔ¿ÁÂÈ ÙÔÓ ‰È·¯ˆÚÈÛÌfi ÙˆÓ ¯ÚˆÌ·- Ì·ÙÔ˜, ‰ËÏ·‰‹ ÙÔ ·ÓÙÈÁfiÓÔ ¤Ó·ÓÙÈ ÙÔ˘ ÔÔ›Ô˘ ÛÙÚ¤- ÙÔÛˆÌ¿ÙˆÓ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ̛وÛ˘. ™Ùfi¯ÔÈ ÊÂÙ·È, Ì ¿ÏϘ ÌÂıfi‰Ô˘˜. °È· ÙÔÓ ÏfiÁÔ ·˘Ùfi ÛÙ· ıÂ- ÙÔ˘˜ Â›Ó·È Ù¤ÛÛÂÚ· ·ÓÙÈÁfiÓ· ÙÔ˘ ÎÂÓÙÚÔÌÂÚȉ›Ô˘/ÎÈ- ÙÈο ∞¡∞ ·ÎÔÏÔ˘ı› Ô ÚÔÛ‰ÈÔÚÈÛÌfi˜ ÙˆÓ ·ÓÙÈÛˆ- ÓËÙfi¯ˆÚÔ˘, Ù· ÔÏ˘ÂÙ›‰È· CENP-A, CENP-B, Ì¿ÙˆÓ Ô˘ ÛÙÚ¤ÊÔÓÙ·È ¤Ó·ÓÙÈ ÙˆÓ ENAs ·ÓÙÈÁfiÓˆÓ. CENP-C, CENP-D. Δ· ·ÓÙÈÎÂÓÙÚÔÌÂÚȉȷο ·ÓÙÈÛÒ- Δ· ·ÓÙÈÛÒÌ·Ù· ·˘Ù¿ ‰ÚÔ˘Ó ¤Ó·ÓÙÈ ÌÈÎÚÒÓ ˘ÚË- Ì·Ù· ¤Ó·ÓÙÈ ÙÔ˘ CENP-B Â›Ó·È Ù· Û˘¯ÓfiÙÂÚ· ··- ÓÈÎÒÓ Î·È Î˘ÙÙ·ÚÔÏ·ÛÌ·ÙÈÎÒÓ ÚÈ‚ÔÓÔ˘ÎÏÂÔÚˆÙÂ˚- ÓÙÒÌÂÓ· Î·È Ì ÙÔ˘˜ ˘„ËÏfiÙÂÚÔ˘˜ Ù›ÙÏÔ˘˜9. ∏ ·Ó›- ÓÒÓ (sn RNP/sc RNP), ‰ËÏ·‰‹ ÛÙfi¯ÔÈ ÙÔ˘˜ Â›Ó·È ÌË ¯ÓÂ˘Û‹ ÙÔ˘˜ Á›ÓÂÙ·È Ì ¤ÌÌÂÛÔ ·ÓÔÛÔÊıÔÚÈÛÌfi Û ÈÛÙÔÓÈΤ˜ ÚˆÙ½Ó˜ Ô˘ ‚Ú›ÛÎÔÓÙ·È Û ۇÌÏÔη Ì ÌÈÙˆÙÈο ·ÙÙ·Ú· ∏∂ƒ-2, ELISA Î·È ·ÓÔÛÔ·ÔÙ‡ˆ- ÌÈÎÚ¿ ÌfiÚÈ· RNA. ¶ÔÏÏ¿ ·fi Ù· ·ÓÙÈÁfiÓ· ·˘Ù¿ Â›Ó·È ÛË. ™ÙÔÓ ¤ÌÌÂÛÔ ·ÓÔÛÔÊıÔÚÈÛÌfi ÂÌÊ·Ó›˙Ô˘Ó ÛÙÈÎÙfi ‰È·Ï˘Ù¿ ηÈ, ÂÂȉ‹ Ï·Ì‚¿ÓÔÓÙ·È ·fi Âί‡ÏÈÛË ˘Ú‹- Ù‡Ô ÊıÔÚÈÛÌÔ‡ Ì ÙË ‰È·ÊÔÚ¿ fiÙÈ Ô ·ÚÈıÌfi˜ ÙˆÓ ÓˆÓ Î˘ÙÙ¿ÚˆÓ, ÔÓÔÌ¿˙ÔÓÙ·È Âί˘ÏÈ˙fiÌÂÓ· ˘ÚËÓÈο ÎÔÎΛˆÓ ·ÓÙÈÛÙÔȯ› ÛÙÔÓ ·ÚÈıÌfi ÙˆÓ ÎÂÓÙÚÔÌÂÚÈ- ·ÓÙÈÁfiÓ· (Extractable Nuclear Antigens, ENA). Δ· ‰›ˆÓ. ΔÔ ÎÂÓÙÚÔÌÂÚ›‰ÈÔ Â›Ó·È Ë ÂÚÈÔ¯‹ ÂÚ›ÛÊÈÁ͢ ENAs ·ÓÙÈÛÒÌ·Ù· Û¯ÂÙ›˙ÔÓÙ·È Ì ÙÔÓ ÛÙÈÎÙfi Ù‡Ô ÙÔ˘ ¯ÚˆÌ·ÙÔÛÒÌ·ÙÔ˜ Ô˘ Û˘ÁÎÚ·Ù› ÙȘ ‰˘Ô ¯Úˆ- ÊıÔÚÈÛÌÔ‡ Î·È Ù· ÈÔ ÁÓˆÛÙ¿ ·ÓÙÈÁfiÓ· ¤Ó·ÓÙÈ ÙˆÓ Ì·Ù›‰Â˜. ™Â ÌÈÙˆÙÈο ·ÙÙ·Ú· ÛÙË Ê¿ÛË Ù˘ ÌÂÙ¿Ê·- Û˘ Ù· ·ÓÙÈÎÂÓÙÚÔÌÂÚȉȷο ·ÓÙÈÛÒÌ·Ù· Ê·›ÓÔÓÙ·È Û ÔÔ›ˆÓ ÛÙÚ¤ÊÔÓÙ·È Â›Ó·È Ù·: Sm, U1nRNP, SS-A (Ro), ÛÂÈÚ¿ οıÂÙ· ÛÙÔÓ ÂÈÌ‹ÎË ¿ÍÔÓ· Ù˘ ÂÚÈÔ¯‹˜ ÙÔ˘ SS-B (La), Scl-70, Jo-1. √È Û˘Ó‹ıÂȘ ̤ıÔ‰ÔÈ ÁÈ· ÙËÓ ¯ÚˆÌ·ÙÔÛÒÌ·ÙÔ˜10,11. ΔÔ ·˘ÙÔ·Óٛۈ̷ ·˘Ùfi ıˆ- ·Ó›¯Ó¢ÛË ÙˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ·˘ÙÒÓ Â›Ó·È: 1) Ë ·ÓÔÛÔ- ÚÂ›Ù·È Î·Ïfi˜ ‰È·ÁÓˆÛÙÈÎfi˜ ‰Â›ÎÙ˘ ÛÙÔ ÂÚÈÔÚÈṲ̂ÓÔ ‰È¿¯˘ÛË (ID), 2) Ë ·ÓÙ›ıÂÙË ËÏÂÎÙÚÔÊfiÚËÛË (CIE), 3) ÛÎÏËÚfi‰ÂÚÌ· (CREST) 60-90%, ÂÓÒ ·ÓȯÓ‡ÂÙ·È Â›- ÔÈ Ú·‰ÈÔ˚ÛÔÙÔÈΤ˜ ̤ıÔ‰ÔÈ (RIA), 4) Ë ·ÓÔÛÔÂÓ˙˘- Û˘ ÛÙÔ ‰È¿¯˘ÙÔ ÛÎÏËÚfi‰ÂÚÌ· 12% Î·È ÛÙÔ Û‡Ó- ÌÈ΋ ̤ıÔ‰Ô˜ (ELISA), 5) Ë ·ÓÔÛÔ·ÔÙ‡ˆÛË (IB) ‰ÚÔÌÔ Raynaud 20%. Î·È 6) Ë ·ÓÔÛÔηı›˙ËÛË (πƒ).
∞ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÚÈ‚Ôۈ̷ÙÈÎÒÓ ∞ÓÙÈ-U1RNP Î·È ·ÓÙÈ-Sm ·ÓÙÈÛÒÌ·Ù· ÚˆÙÂ˚ÓÒÓ P (antiribosomal pho- Δ· ·˘ÙÔ·ÓÙÈÁfiÓ· ¤Ó·ÓÙÈ ÙˆÓ ÔÔ›ˆÓ ÛÙÚ¤ÊÔÓÙ·È Ù· sphoprotein P antibodies, anti-RPP) ·ÓÙÈÛÒÌ·Ù· ·˘Ù¿ Â›Ó·È ÌÈÎÚ¤˜ ˘ÚËÓÈΤ˜ ÚÈ‚ÔÓÔ˘ÎÏÂ- ÔÚˆÙ½Ó˜ snRNP. Δ· ·ÓÙÈ-U RNP ·ÓÙÈÛÒÌ·Ù· ·Ó·- Δ· anti-RPP ÛÙÚ¤ÊÔÓÙ·È ¤Ó·ÓÙÈ ÙˆÓ ÚˆÙÂ˚ÓÒÓ P (P0, 1 P1, P2, Ì MB 38, 19, 17 kDa ·ÓÙ›ÛÙÔȯ·) Ô˘ ‚Ú›- ÁÓˆÚ›˙Ô˘Ó Î·È ·ÓÙȉÚÔ‡Ó Î˘Ú›ˆ˜ Ì ٷ ÂȉÈο 70kD, ÛÎÔÓÙ·È ÛÙ· ÚÈ‚ÔÛÒÌ·Ù· ÙˆÓ Â˘Î·ÚȈÙÈÎÒÓ Î˘ÙÙ¿- 33kD (A) Î·È 20 kD (C) ÔÏ˘ÂÙ›‰È· Ô˘ ‚Ú›ÛÎÔ- ÚˆÓ. ∫ÔÈÓfi˜ ›ÙÔÔ˜ Î·È ÁÈ· ÙȘ ÙÚÂȘ ÚˆÙ½Ó˜ ›- ÓÙ·È Û ۇÌÏÂÁÌ· Ì ¤ÓÙ ÌÈÎÚ¿ ÌfiÚÈ· snRNA Ó·È ¤Ó· ÎÔÈÓfi ÂÙ›‰ÈÔ 22 ·ÌÈÓÔͤˆÓ. Δ· ·ÓÙÈÛÒÌ·Ù· (U1,U2,U4,U5,U6). Δ· ·ÓÙÈÛÒÌ·Ù· ·˘Ù¿ ·ÔÙÂÏÔ‡Ó ·˘Ù¿ ·ÓȯÓ‡ÔÓÙ·È ÛÙÔ 8-12% ÙˆÓ ·ÛıÂÓÒÓ Ì ™∂§, ‰È·ÁÓˆÛÙÈÎfi ‰Â›ÎÙË ÁÈ· ÙË MÈÎÙ‹ NfiÛÔ ÙÔ˘ ™˘Ó‰ÂÙÈ- ÛÙÔ 30% ÙˆÓ ·ÛıÂÓÒÓ Ì ™ÎÏËÚfi‰ÂÚÌ· Î·È ÂÈÎ¿Ï˘- ÎÔ‡ πÛÙÔ‡ (ª¡™π), ·ÓȯÓ‡ÔÓÙ·È fï˜ Î·È ÛÙÔ 30- „Ë §‡ÎÔ˘ Î·È ÛÙÔ 50-90% ÙˆÓ ·ÛıÂÓÒÓ Ì 懯ˆÛË 40% ÙˆÓ ·ÛıÂÓÒÓ Ì ™∂§ fiÔ˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ·- §‡ÎÔ˘ (˘„ËÏÔ› Ù›ÙÏÔÈ ÚÔÛ‰ÈÔÚ›˙ÔÓÙ·È ÚÈÓ Î·È Î·Ù¿ Ô˘Û›· ÓÂÊÚÈ΋˜ ‚Ï¿‚˘ Î·È Û˘ÌÙÒÌ·Ù· fiˆ˜ ·Ú- 13 ÙË ‰È¿ÚÎÂÈ· ÂÓÂÚÁÔ‡˜ ÓfiÛÔ˘)12. ıÚ·ÏÁ›Â˜, ·ıÚ›Ùȉ˜, Ê·ÈÓfiÌÂÓÔ Raynaud . Δ· ·ÓÙÈ-Sm ·ÓÙÈÛÒÌ·Ù· ·ÓÙȉÚÔ‡Ó Ì ٷ ÔÏ˘- ′ ∞ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÌË ÈÛÙÔÓÈÎÒÓ ˘- ÂÙ›‰È· B (28kD), B (29kD) Î·È D (16kD) Ô˘ ‚Ú›- ÚËÓÈÎÒÓ Î·È Î˘ÙÙ·ÚÔÏ·ÛÌ·ÙÈÎÒÓ ÛÎÔÓÙ·È Â›Û˘ Û ÚÈ‚ÔÓÔ˘ÎÏÂÔÚˆÙÂ˚ÓÈο Û‡ÌÏÔη ÚˆÙÂ˚ÓÒÓ (Extractable Nuclear An- Ì·˙› Ì ÌÈÎÚ¿ ÌfiÚÈ· sn RNA.. Δ· ·ÓÙÈ-Sm ·ÓÙÈÛÒÌ·- Ù· ıˆÚÔ‡ÓÙ·È ÂȉÈÎfi˜ ‰È·ÁÓˆÛÙÈÎfi˜ ‰Â›ÎÙ˘ ÛÙÔÓ tigens-ENAs) ™∂§ Î·È ·ÓȯÓ‡ÔÓÙ·È ÛÙÔ 30-40% ÙˆÓ ·ÛıÂÓÒÓ9,14. ŸÙ·Ó Ù· ANA Â›Ó·È ·ÚÓËÙÈο Ì ÙË Ì¤ıÔ‰Ô ÙÔ˘ IIF ™ÙÔÓ ÔÚfi Û˘Ó‹ıˆ˜ Û˘Ó˘¿Ú¯Ô˘Ó Ì ٷ ·ÓÙÈ-U1n ‰ÂÓ ·ÎÔÏÔ˘ı› ÂÚ·ÈÙ¤Úˆ ¤ÏÂÁ¯Ô˜ ÂÎÙfi˜ Â¿Ó Ë ÎÏÈÓÈ- RNP ·-ÓÙÈÛÒÌ·Ù·. ™ÙÔÓ ¤ÌÌÂÛÔ ·ÓÔÛÔÊıÔÚÈÛÌfi Î·È Î‹ ÂÈÎfiÓ· Û˘ÓËÁÔÚ› ÁÈ· οÔÈÔ APN, ÔfiÙÂ Ë ‰È·‰È- ÔÈ ‰‡Ô Ù‡ÔÈ ÙˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ‰›ÓÔ˘Ó ÏÂÙfi ÛÙÈÎÙfi ηۛ· ·ӷϷ̂¿ÓÂÙ·È Ì ¿ÏÏÔ ˘fiÛÙڈ̷ Î·È ¿Ï- ÊıÔÚÈÛÌfi. 46 ∂ÚÁ·ÛÙËÚȷ΋ ÚÔÛ¤ÁÁÈÛË ·˘ÙÔ¿ÓÔÛˆÓ ÚÂ˘Ì·ÙÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ
∞ÓÙÈ-SS/A (Ro) Î·È ·ÓÙÈ-SS/μ (La) ∞ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙÔ˘ ΢ÙÙ·ÚÔÏ¿- ·ÓÙÈÛÒÌ·Ù· ÛÌ·ÙÔ˜ ÙˆÓ Ô˘‰ÂÙÂÚÔÊ›ÏˆÓ (Anti- neutrophil cytoplasmic antibodies- Δ· ·ÓÙÈ-Ro ·ÓÙÈÛÒÌ·Ù· ÛÙÚ¤ÊÔÓÙ·È ¤Ó·ÓÙÈ ÙˆÓ Úˆ- ÙÂ˚ÓÒÓ 60 kD Î·È 52 kD Ô˘ ‚Ú›ÛÎÔÓÙ·È Û ۇÌÏÂÁ- ANCA) Ì· Ì ˘ÚËÓÈο Ôͤ· ÏÔ‡ÛÈ· Û ԢÚȉ›ÓË. ∞ÓȯÓ‡- Δ· ·˘ÙÔ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙÔ˘ ΢ÙÙ·ÚÔÏ¿ÛÌ·ÙÔ˜ ÔÓÙ·È Î˘Ú›ˆ˜ Û ·ÛıÂÓ›˜ Ì ۇӉÚÔÌÔ Sjögren (60 ÙˆÓ Ô˘‰ÂÙÂÚÔÊ›ÏˆÓ ·ÔÙÂÏÔ‡Ó ÂÙÂÚÔÁÂÓ‹ ÔÌ¿‰· 15 %) Î·È ™∂§ (35-50%) , ·ÏÏ¿ Î·È Û ¿ÏÏ· ∞ƒ¡.. ™˘Ó- ·ÓÙÈÛˆÌ¿ÙˆÓ Ô˘ ·ÓÙȉÚÔ‡Ó Ì ·ÓÙÈÁfiÓ·/ÚˆÙ½Ó˜ ‰¤ÔÓÙ·È Â›Û˘ Ì ÔÚÈṲ̂Ó˜ ÌÔÚʤ˜ Ù˘ ÓfiÛÔ˘ fi- ÙˆÓ ÚˆÙÔÁÂÓÒÓ Î·È ‰Â˘ÙÂÚÔÁÂÓÒÓ ÎÔÎΛˆÓ ÙˆÓ Ô˘- ˆ˜ Ì ÙÔÓ ˘Ô͇ ‰ÂÚÌ·ÙÈÎfi χÎÔ, ÙÔÓ ÓÂÔÁÓÈÎfi χ- ‰ÂÙÂÚÔÊ›ÏˆÓ ÔÏ˘ÌÔÚÊÔ˘Ú‹ÓˆÓ. ÎÔ Î·È ÙÔÓ Ï‡ÎÔ Ô˘ ÂÌÊ·Ó›˙ÂÙ·È ÛÙËÓ ÔÌfi˙˘ÁÔ ·ÓÂ- ªÂ ÙË Ì¤ıÔ‰Ô ÙÔ˘ ¤ÌÌÂÛÔ˘ ·ÓÔÛÔÊıÔÚÈÛÌÔ‡ ¿ÚÎÂÈ· ÙˆÓ ·Ú·ÁfiÓÙˆÓ ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ C2 Î·È Ì ˘fiÛÙڈ̷ Ô˘‰ÂÙÂÚfiÊÈÏ·, ÌÔÓÈÌÔÔÈË̤ӷ Î·È C4. Ì ·Èı˘ÏÈ΋ ·ÏÎÔfiÏË ‰È·ÎÚ›ÓÔÓÙ·È ÙÚÂȘ Ù‡ÔÈ ÊıÔÚÈ- Δ· ·ÓÙÈ-La ·ÓÙÈÛÒÌ·Ù· ÛÙÚ¤ÊÔÓÙ·È ¤Ó·ÓÙÈ Êˆ- ÛÌÔ‡ ÙˆÓ ANCA. √ ΢ÙÙ·ÚÔÏ·ÛÌ·ÙÈÎfi˜ (cyttopla- ÛÊÔÚˆÙ½Ó˘ 48kD Ë ÔÔ›· ‚Ú›ÛÎÂÙ·È Û ۇÌÏÂÁ- smic), Ì ÎÔÎÎÈÒ‰Ë ¯ÚÒÛË ÙÔ˘ ΢ÙÙ·ÚÔÏ¿ÛÌ·ÙÔ˜ Ì· Ì ·ÓÙ›ÁÚ·Ê· RNA ÔÏ˘ÌÂÚ¿Û˘ III. Δ· ·ÓÙÈ-La Ô˘ ·ÓÙÈÛÙÔȯ› ÛÙ· c-ANCA Ô˘ ·ÓÙȉÚÔ‡Ó Î˘Ú›ˆ˜ ·ÓÙÈÛÒÌ·Ù· ·ÔÙÂÏÔ‡Ó ÔÚÔÏÔÁÈÎfi ‰Â›ÎÙË ÁÈ· ÙÔ Û‡Ó- Ì ÙËÓ ÚˆÙÂ˚Ó¿ÛË–3 ÙˆÓ ·-ÎÔÎΛˆÓ20. √ ÂÚÈ˘ÚË- ‰ÚÔÌÔ Sjögren (40-60%), ·ÓȯÓ‡ÔÓÙ·È fï˜ Î·È ÛÙÔ ÓÈÎfi˜ ÊıÔÚÈÛÌfi˜ (perinuclear) Ì ÂÚÈ˘ÚËÓÈ΋ ¯ÚÒ- 16 ™∂§ (10-15%) . ∏ ·ÚÔ˘Û›· ÙˆÓ ·ÓÙÈ-Ro Î·È ·ÓÙÈ-La ÛË Ô˘ ·ÓÙÈÛÙÔȯ› ÛÙ· p-ANCA, Ù· ÔÔ›· ÛÙÔ ÌÂ- ·ÓÙÈÛˆÌ¿ÙˆÓ ÛÙÔ Û‡Ó‰ÚÔÌÔ Sjögren Û¯ÂÙ›˙ÂÙ·È Ì Á·Ï‡ÙÂÚÔ ÔÛÔÛÙfi ÙÔ˘˜ ‰ÚÔ˘Ó ¤Ó·ÓÙÈ Ù˘ Ì˘ÂÏÔ¸Â- Â͈·‰ÂÓÈΤ˜ ÂΉËÏÒÛÂȘ Ù˘ ÓfiÛÔ˘. ÚÔÍÂȉ¿Û˘21, Î·È Ô ¿Ù˘Ô˜ ÊıÔÚÈÛÌfi˜ Ì ‰È¿¯˘ÙË ¯ÚÒÛË ÙÔ˘ ΢ÙÙ·ÚÔÏ¿ÛÌ·ÙÔ˜ Ô˘ ·ÊÔÚ¿ Ù· a ‹ x- ∞ÓÙÈ-Scl-70 ‹ ·ÓÙÈ-ÙÔÔ˚ÛÔÌÂÚ¿ÛË π ANCA Ô˘ Â›Ó·È ÂȉÈο ¤Ó·ÓÙÈ Ù˘ Ï˘ÛÔ˙‡Ì˘, ÂÏ·- ·ÓÙÈÛÒÌ·Ù· ÛÙ¿Û˘, Ï·ÎÙÔÊÂÚ›Ó˘, ηı„›Ó˘-G, BPI (bacterial Δ· ·ÓÙÈ-ÙÔÔ˚ÛÔÌÂÚ¿ÛË π ·ÓÙÈÛÒÌ·Ù· ÛÙÚ¤ÊÔÓÙ·È permeability increasing protein), ‚-ÁÏ˘ÎÔ˘ÚÔÓȉ¿Û˘ ¤Ó·ÓÙÈ Ù˘ DNA ÙÔÔ˚ÛÔÌÂÚ¿Û˘ π Ô˘ ¤¯ÂÈ ªμ 100 Î·È ÂÓÔÏ¿Û˘. ∂¿Ó Ù· ANCA Â›Ó·È ıÂÙÈο ÛÙÔÓ ·ÓÔ- kD. ∏ ·Ú¯È΋ ÙÔ˘˜ ÔÓÔÌ·Û›· ‹Ù·Ó ·ÓÙÈ-Scl-70 ·ÓÙÈ- ÛÔÊıÔÚÈÛÌfi ·ÎÔÏÔ˘ı› Ë ‰È¢ÎÚ›ÓÈÛË Ù˘ ÂȉÈÎfiÙË- ÛÒÌ·Ù· ‰ÈfiÙÈ ıˆڋıËΠfiÙÈ ÛÙfi¯Ô˜ ÙÔ˘˜ ‹Ù·Ó ÌÈ· Ù¿˜ ÙÔ˘ Ì ELISA ΢ڛˆ˜ ¤Ó·ÓÙÈ ·ÓÙÈÁfiÓˆÓ fiˆ˜ Ë ÚˆÙ½ÓË ÙÔ˘ ˘Ú‹Ó· Ì ªμ 70 kD. Δ· ·ÓÙÈ-ÙÔÔ˚ÛÔ- Ì˘ÂÏÔ¸ÂÚÔÍÂȉ¿ÛË (MPO) Î·È Ë ÚˆÙÂ˚Ó¿ÛË 3 ÌÂÚ¿ÛË π ·ÓÙÈÛÒÌ·Ù· ·ÓȯÓ‡ÔÓÙ·È ÛÙÔ 70-75% ÙˆÓ (PR3). ∂›Û˘ fiÙ·Ó ÛÙÔÓ ·ÓÔÛÔÊıÔÚÈÛÌfi ˘¿Ú¯Ô˘Ó ·ÛıÂÓÒÓ Ì ‰È¿¯˘ÙÔ ÛÎÏËÚfi‰ÂÚÌ· Î·È ıˆÚÔ‡ÓÙ·È P-ANCA ıÂÙÈο Î·È ∞¡∞ ıÂÙÈο, ı· Ú¤ÂÈ Ó· Á›ÓÂÈ ÔÚÔÏÔÁÈÎfi˜ ‰Â›ÎÙ˘ Ù˘ ÓfiÛÔ˘9,17. ¶·Ú·ÙËÚÔ‡ÓÙ·È ·- ·ϋı¢ÛË Ù˘ ıÂÙÈÎfiÙËÙ·˜ ÙˆÓ P-ANCA Û ˘fi- ÎfiÌË ÛÙÔ 4-18% ÙˆÓ ·ÛıÂÓÒÓ Ì ÂÚÈÔÚÈṲ̂ÓÔ ÛÙڈ̷ Ô˘‰ÂÙÂÚÔÊ›ÏˆÓ ÌÔÓÈÌÔÔÈËÌ¤ÓˆÓ Ì ÊÔÚ- ÛÎÏËÚfi‰ÂÚÌ· (Û‡Ó‰ÚÔÌÔ CREST) ηıÒ˜ Î·È ÛÙÔ 5% Ì·Ï‰Â˛‰Ë, fiÔ˘ Ù· ·ÏËı‹ P-ANCA ‰›ÓÔ˘Ó ÎÔÎÎÈÒ‰Ë ÂÚ›Ô˘ ÙˆÓ ·ÛıÂÓÒÓ Ì ۇӉÚÔÌÔ Raynaud. ∏ ·Ó›- ΢ÙÙ·ÚÔÏ·ÛÌ·ÙÈÎfi ÊıÔÚÈÛÌfi. ¯ÓÂ˘Û‹ ÙÔ˘˜ Ê·›ÓÂÙ·È fiÙÈ ¤¯ÂÈ ÚÔÁÓˆÛÙÈ΋ ÛËÌ·Û›· ∏ ·Ó›¯Ó¢ÛË ÙˆÓ ANCA ¤¯ÂÈ ÛËÌ·ÓÙÈ΋ ·Í›· ÁÈ· ·ÊÔ‡ Ë ·ÚÔ˘Û›· ÙÔ˘˜ ÛÙÔÓ ÔÚfi Û ¿ÙÔÌ· ¢ÚÈÛÎfi- ÙË ‰È¿ÁÓˆÛË Î·È ÎÏÈÓÈ΋ ·Ú·ÎÔÏÔ‡ıËÛË ·ÛıÂÓÒÓ Ì ÌÂÓ· ÛÙ· ·Ú¯Èο ÛÙ¿‰È·, ¤‰ÂÈÍ fiÙÈ ÛÙËÓ ÔÚ›· ·Ó¤- ÓÂÎÚˆÙÈ΋ Û˘ÛÙËÌ·ÙÈ΋ ·ÁÁÂÈ›Ùȉ·, fiˆ˜ Ë ÎÔÎÎȈ̿- Ù˘Í·Ó Ï‹Ú˜ ÛÎÏËÚfi‰ÂÚÌ·. ™ÙÔÓ ¤ÌÌÂÛÔ ·ÓÔÛÔ- ÙˆÛË Wegener, Ë ÌÈÎÚÔÛÎÔÈ΋ ÔÏ˘·ÚÙËÚ›Ùȉ·, Î·È ÊıÔÚÈÛÌfi ·Ú·ÙËÚÂ›Ù·È ‰È¿¯˘ÙÔ˜ ÏÂÙfi˜ ÊıÔÚÈÛÌfi˜ ÙÔ Û‡Ó‰ÚÔÌÔ Churg-Strauss22,23. Δ· ANCA ·ÓȯÓ‡- ÙÔ˘ ˘Ú‹Ó· Î·È ÊıÔÚÈÛÌfi˜ ÙˆÓ ˘ÚËÓ›ÛΈÓ. ÔÓÙ·È Â›Û˘ Û ·ÛıÂÓ›˜ Ì ȉÈÔ·ı‹ ÓÂÎÚˆÙÈ΋ ÛÂÈÚ·Ì·ÙÔÓÂÊÚ›Ùȉ·, ÛÙÔÓ ™∂§, ÙË ÚÂ˘Ì·ÙÔÂȉ‹ ·Ú- ∞ÓÙÈ-Jo-1 ·ÓÙÈÛÒÌ·Ù· ıÚ›Ùȉ·, Û ¿ÏÏ· ÚÂ˘Ì·ÙÈο ÓÔÛ‹Ì·Ù· ηıÒ˜ Î·È Û ÊÏÂÁÌÔÓÒ‰Ë ÓÔÛ‹Ì·Ù· ‹·ÙÔ˜ Î·È ÂÓÙ¤ÚÔ˘24. Δ· ·ÓÙÈ- Jo-1 ·ÓÙÈÛÒÌ·Ù· ÛÙÚ¤ÊÔÓÙ·È ¤Ó·ÓÙÈ ÂÓfi˜ Ô- Ï˘ÂÙȉ›Ô˘ Ì ªμ 50kD Ô˘ ·Ó·ÁÓˆÚ›ÛıËΠfiÙÈ Â›Ó·È ƒÂ˘Ì·ÙÔÂȉ›˜ ·Ú¿ÁÔÓÙ˜ Ë Û˘ÓıÂÙ¿ÛË ÙÔ˘ t-RNA Ù˘ ÈÛÙȉ›Ó˘. Δ· ·ÓÙÈÛÒÌ·Ù· ·˘Ù¿ Â›Ó·È Ù· Û˘¯ÓfiÙÂÚ· ··ÓÙÒÌÂÓ· ÛÙË Ì˘ÔÛ›Ùȉ· √È ƒÂ˘Ì·ÙÔÂȉ›˜ ¶·Ú¿ÁÔÓÙ˜ (ƒ¶) Â›Ó·È ·˘ÙÔ·ÓÙÈ- Î·È ·ÓȯÓ‡ÔÓÙ·È ÂÚ›Ô˘ ÛÙÔ 25 % ÙˆÓ ·ÛıÂÓÒÓ18,19. ÛÒÌ·Ù· ¤Ó·ÓÙÈ ÂÈÙfiˆÓ ÙÔ˘ Fc ÙÌ‹Ì·ÙÔ˜ Ù˘ IgG ™ÙÔÓ ¤ÌÌÂÛÔ ·ÓÔÛÔÊıÔÚÈÛÌfi ·Ú·ÙËÚÂ›Ù·È ‰È¿¯˘ÙÔ˜ ·ÓÔÛÔÛÊ·ÈÚ›Ó˘ Î·È ‰È·ÎÚ›ÓÔÓÙ·È ÙÚÂȘ ΢ڛˆ˜ ÈÛfiÙ˘- ÏÂÙfi˜ ÊıÔÚÈÛÌfi˜ ÙÔ˘ ΢ÙÙ·ÚÔÏ¿ÛÌ·ÙÔ˜. ÔÈ (IgM, IgA, IgG). ™Ù· ÎÏÈÓÈο ÂÚÁ·ÛÙ‹ÚÈ· ÚÔÛ‰ÈÔ- A. ¶·˘Ï›ÙÔ˘-ΔÛÈfiÓÙÛË 47
Ú›˙ÂÙ·È Û˘Ó‹ıˆ˜ Ô IgM ƒ¶ Ô ÔÔ›Ô˜ ·ÔÙÂÏ› ‰È·- Δ· ∞º∞ Ô˘ ¤¯Ô˘Ó ·ÍÈÔÏÔÁËı› ÎÏÈÓÈο ̤¯ÚÈ ÁÓˆÛÙÈÎfi ÎÚÈÙ‹ÚÈÔ ÁÈ· ÙË ÚÂ˘Ì·ÙÔÂȉ‹ ·ÚıÚ›Ùȉ· Û‹ÌÂÚ· ˆ˜ ÈÛ¯˘Úfi˜ ·Ú¿ÁÔÓÙ·˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ıÚfiÌ- (ƒ∞) ·Ú¿ ÙÔ fiÙÈ ‰ÂÓ Â›Ó·È ÂȉÈÎfi˜ ‰Â›ÎÙ˘ Ù˘ ÓfiÛÔ˘ ‚ˆÛË Î·È ÂÈÏÔΤ˜ Ù˘ ·ËÛ˘, Â›Ó·È ÙÔ ·ÓÙÈËÎÙÈÎfi (¢·ÈÛıËÛ›· 60-80%, ÂȉÈÎfiÙËÙ· 70%), ·ÊÔ‡ ·ÓȯÓ‡- ÙÔ˘ χÎÔ˘ (Lupus Anticoagulant, LA), Ù· ·ÓÙÈηډÈÔ- ÂÙ·È Î·È Û ¿ÏÏ· ∞ƒ¡ ηıÒ˜ Î·È Û ˘ÁÈ‹ ¿ÙÔÌ·. ™Â ÏÈÈÓÈο (anti-cardiolipin, aCL) ·ÓÙÈÛÒÌ·Ù· Î·È Ù· ·ÓÙÈ- fi,ÙÈ ·ÊÔÚ¿ ÙËÓ ÚfiÁÓˆÛË, Û˘Ó‰¤ÂÙ·È Ì ÙË ÛÔ‚·Úfi- ÛÒÌ·Ù· ¤Ó·ÓÙÈ Ù˘ ‚2 ÁÏ˘ÎÔÚˆÙ½Ó˘ π (anti-‚2GPI, ÙËÙ· Ù˘ ÓfiÛÔ˘ Î·È ˘„ËÏÔ› Ù›ÙÏÔÈ ‰Â›¯ÓÔ˘Ó ‰È·‚ÚˆÙÈ- a‚2GPI). Δ· ·ÓÙÈÛÒÌ·Ù· Ì ‰Ú¿ÛË LA Â›Ó·È ÂÙÂÚÔÁÂ- Τ˜ ‚Ï¿‚˜ Î·È ÁÚ‹ÁÔÚË ÂͤÏÈÍË Ù˘ ÓfiÛÔ˘ Ì ¯ÂÈ- Ó‹˜ ÔÌ¿‰· ·ÓÙÈÛˆÌ¿ÙˆÓ Ô˘ ÛÙÚ¤ÊÔÓÙ·È ¤Ó·ÓÙÈ Úˆ- ÚfiÙÂÚË ¤Î‚·ÛË. £· Ú¤ÂÈ Ó· ÛËÌÂȈı› fiÙÈ Ô IgM ÙÂ˚ÓÒÓ ÙÔ˘ Ï¿ÛÌ·ÙÔ˜ (΢ڛˆ˜ ‚2GPI Î·È ÚÔıÚÔÌ- ƒ¶ ‰ÂÓ ·ÓȯÓ‡ÂÙ·È ÛÙÔ 30% ÙˆÓ ·ÛıÂÓÒÓ Û ÚÒÈ- ‚›ÓË) ÔÈ Ôԛ˜ Â›Ó·È Û˘Ó‰Â‰Â̤Ó˜ Ì ʈÛÊÔÏÈ›‰È· ÌË ƒ∞. Î·È Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙËÓ ‹ÍË30. Δ· ·ÓÙÈÛÒÌ·Ù· ·˘Ù¿ ·Ú·Ù›ÓÔ˘Ó ÙȘ ÂÍ·ÚÙÒÌÂÓ˜ ·fi Ù· ʈÛÊÔÏÈ›‰È· AÓÙÈ-CCP ·ÓÙÈÛÒÌ·Ù· (Anti-Cyclic ‰ÔÎÈ̷ۛ˜ ‹Í˘ (in vitro) ÁÈ’ ·˘Ùfi Î·È ·ÓȯÓ‡ÔÓÙ·È Citrullinated peptides Abs) Ì ÙȘ ‰ÔÎÈ̷ۛ˜ ·˘Ù¤˜ (aPTT, ∫CΔ, dRVVT). Δ· aCL ·ÓÙÈÛÒÌ·Ù· ‰È·ÎÚ›ÓÔÓÙ·È Û ÌË ÂÍ·ÚÙÒ- ∂›Ó·È ÁÓˆÛÙfi fiÙÈ Ë ÚÔÛ‚ÔÏ‹ Ù˘ ¿ÚıÚˆÛ˘ ÚÔË- ÌÂÓ· ·fi ÙË ‚2GPI, Ô˘ Û˘Ó‰¤ÔÓÙ·È Î˘Ú›ˆ˜ Ì ÏÔÈ- ÁÂ›Ù·È 1-2 ¯ÚfiÓÈ· ÚÈÓ ÙË ‰È¿ÁÓˆÛË Ù˘ ƒ∞, ηıÒ˜ ÌÒÍÂȘ, Î·È Û aCL ·ÓÙÈÛÒÌ·Ù· ÂÍ·ÚÙÒÌÂÓ· ·fi ÙË Â›Û˘ fiÙÈ ÙÔ 20-30% ·ÛıÂÓÒÓ Ì ƒ∞ ¯ˆÚ›˜ ıÂÚ·- ‚2GPI,, Ô˘ ¤¯Ô˘Ó Û¯¤ÛË Ì ıÚÔÌ‚ÒÛÂȘ Î·È ·Ô‚Ô- ›· ÂÌÊ·Ó›˙ÂÈ ÌfiÓÈÌË ÏÂÈÙÔ˘ÚÁÈ΋ ·Ó·ËÚ›· 2-3 ¯Úfi- Ϥ˜. ¶Ôχ ÛÔ‚·Úfi ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ ÁÈ· ıÚfiÌ‚ˆ- ÓÈ· ÌÂÙ¿ ÙË ‰È¿ÁÓˆÛË. Δ· ‰Â‰Ô̤ӷ ·˘Ù¿ ηıÈÛÙÔ‡Ó ÛË ·ÔÙÂÏÔ‡Ó Â›Û˘ Ù· ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ Ù˘ Âχ- ۷ʤ˜ ÙÔ fiÛÔ ÛËÌ·ÓÙÈ΋ Â›Ó·È Ë ÚÒÈÌË ‰È¿ÁÓˆÛË ıÂÚ˘ ‚2GPI31. ΔfiÛÔ Ù· aCL fiÛÔ Î·È Ù· a‚2GP ·ÓÙÈ- Ù˘ ƒ∞ Ë ÔÔ›· ·ÔÙÂÏ› ÚÔ¸fiıÂÛË ÁÈ· ÙËÓ ÚÒÈ- ÛÒÌ·Ù· ·ÓȯÓ‡ÔÓÙ·È Ì ÚÔÙ˘ÔÔÈË̤ÓË ELISA, ÌË ıÂڷ›·. ªÂ ÛÎÔfi ÏÔÈfiÓ ÙËÓ ÚÒÈÌË ‰È¿ÁÓˆ- fiˆ˜ ÔÚ›˙Ô˘Ó ÔÈ ‰ÈÂıÓ›˜ Ô‰ËÁ›Â˜32-34. ÛË Ù˘ ƒ∞ Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ÌÂÏÂÙ‹ıËÎ·Ó ÔÏÏ¿ ™‡Ìʈӷ Ì fiÏ· fiÛ· ·Ó·Ê¤ÚıËÎ·Ó Ê·›ÓÂÙ·È ·˘ÙÔ·ÓÙÈÛÒÌ·Ù· ÌÂٷ͇ ÙˆÓ ÔÔ›ˆÓ Î·È Ù· ·ÓÙÈÛÒ- fiÙÈ, Ù· ·˘ÙÔ·ÓÙÈÛÒÌ·Ù·, ·Ú¿ ÙÔ fiÙÈ Ù· ÂÚÈÛÛfiÙÂÚ· Ì·Ù· ¤Ó·ÓÙÈ Û˘ÓıÂÙÈÎÒÓ Î˘ÎÏÈÎÒÓ ÎÈÙÚÔ˘ÏÏÈÓˆÌ¤ÓˆÓ ‰Â ·›˙Ô˘Ó Ô˘ÛÈ·ÛÙÈÎfi ·ıÔÁÂÓÂÙÈÎfi ÚfiÏÔ ÛÙ· ∞ƒ¡, ÂÙ›‰ÈˆÓ (·ÓÙÈ-CCP)25. ™‹ÌÂÚ· Ù· ·ÓÙÈ-CCP ·ÓÙÈÛÒ- ÂÓÙÔ‡ÙÔȘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÛÙËÓ ÎÏÈÓÈ΋ Ú·ÎÙÈ΋ ˆ˜ Ì·Ù· ·ÓȯÓ‡ÔÓÙ·È Ì ELISA 2˘-3˘ ÁÂÓÈ¿˜ Î·È ¯ÚË- ‰È·ÁÓˆÛÙÈÎÔ› ‰Â›ÎÙ˜ Î·È ˆ˜ ‰Â›ÎÙ˜ ÚfiÁÓˆÛ˘ Î·È ÛÈÌÔÔÈÔ‡ÓÙ·È, ˆ˜ ‰Â›ÎÙ˘ ‰È¿ÁÓˆÛ˘ ÚÒÈÌ˘ ƒ∞ ÂÓÂÚÁfiÙËÙ·˜ Ù˘ ÓfiÛÔ˘ ·Ó¿ÏÔÁ· Ì ÙËÓ ÂȉÈÎfiÙËÙ¿ (·Ó›¯Ó¢ÛË ÚÈÓ ÙËÓ ¤Ó·ÚÍË ƒ∞) Î·È ˆ˜ ÚÔÁÓˆÛÙÈ- ÙÔ˘˜. ™Ùfi¯Ô˜ ‚¤‚·È· ·Ú·Ì¤ÓÂÈ Ë ‰˘Ó·ÙfiÙËÙ· Ó· Îfi˜ ‰Â›ÎÙ˘ Û ·ÛıÂÓ›˜ Ì ·‰È·ÊÔÚÔÔ›ËÙË ·ÚıÚ›- ÚÔÛ‰ÈÔÚÈÛÙ› ¤Ó· ‹ ÌÂÚÈο ·˘ÙÔ·ÓÙÈÛÒÌ·Ù· ˆ˜ ÂȉÈ- Ùȉ· Ô˘ ı· ·Ó·Ù‡ÍÔ˘Ó ƒ∞26. Δ· ·ÓÙÈ-CCP ·ÓÙÈÛÒ- ÎÔ› ‰Â›ÎÙ˜ ÁÈ· οı ∞ƒ¡ Î·È Ó· ·Ô‰Ôı› ÛÙÔ Î·ı¤- Ì·Ù· ·ÔÙÂÏÔ‡Ó Â›Û˘ Ôχ ηÏfi ‰Â›ÎÙË ‰È¿ÎÚÈÛ˘ Ó· ¤Ó·˜ ÎÂÓÙÚÈÎfi˜ ·ıÔÁÂÓÂÙÈÎfi˜ ÚfiÏÔ˜ ÁÈ· οı Ófi- ‰È·‚ÚˆÙÈ΋˜ ·fi ÌË ‰È·‚ÚˆÙÈ΋ ƒ∞, Ô˘ Á›ÓÂÙ·È Î·- ÛËÌ·. ª¤¯ÚȘ fiÙÔ˘ fï˜ Á›ÓÂÈ ·˘Ùfi ηÙÔÚıˆÙfi, Ë Ï‡ÙÂÚÔ˜ ·Ó Û˘Ó˘¿Ú¯ÂÈ Ì ıÂÙÈÎfi ƒ¶. ™ËÌ·ÓÙÈÎfi ›- ÂÎÙ›ÌËÛË Ù˘ ·ÚÔ˘Û›·˜ ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ Ú¤ÂÈ Ó·È ÙÔ fiÙÈ ·ÓȯÓ‡ÔÓÙ·È ÛÙÔ 38% ÙˆÓ ƒ∞ ·ÛıÂÓÒÓ Ó· Û˘Û¯ÂÙ›˙ÂÙ·È ¿ÓÙ· Ì ÙËÓ ÎÏÈÓÈ΋ ÂÈÎfiÓ·, Ù· ÛÙÔÈ- Ô˘ ¤¯Ô˘Ó ·ÚÓËÙÈÎfi IgM ƒ¶. ∏ ¢·ÈÛıËÛ›· Î·È Ë ÂÈ- ¯Â›· ·Ó¿ÚÎÂÈ·˜ ‹ ‚Ï¿‚˘ ÙÔ˘ ÔÚÁ¿ÓÔ˘-ÛÙfi¯Ô˘ Î·È ‰ÈÎfiÙËÙ· ÙˆÓ ·ÓÙÈ-CCP ·ÓÙÈÛˆÌ¿ÙˆÓ ÁÈ· ÙË ‰È¿ÁÓˆÛË ÙÔ˘˜ ÁÂÓÂÙÈÎÔ‡˜ Î·È Â›ÎÙËÙÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘. Ù˘ ƒ∞ Â›Ó·È 75-80% Î·È 98% ·ÓÙ›ÛÙÔȯ·27. μÈ‚ÏÈÔÁÚ·Ê›· ∞ÓÙÈʈÛÊÔÏÈȉÈο ·ÓÙÈÛÒÌ·Ù· 1. Tan EM. Autoantibodies to Nuclear Antigens (ANA): Their (∞º∞) Immunobiology and Medicine. Adv Immunol 1982; 32: 167-240. Δ· ∞º∞ Â›Ó·È ÌÈ· ÂÙÂÚÔÁÂÓ‹˜ ÔÌ¿‰· ·˘ÙÔ·ÓÙÈۈ̿- 2. Hargraves MM, Richamond H, Morton R. Presentation of ÙˆÓ Ù· ÔÔ›· ·ÓÙȉÚÔ‡Ó Î˘Ú›ˆ˜ Ì ڈÙ½Ó˜ ÙÔ˘ tow bone marrow elements: The “tart” cells and “L.E Ï¿ÛÌ·ÙÔ˜ Ô˘ Û˘Ó‰¤ÔÓÙ·È Ì ·ÚÓËÙÈο ÊÔÚÙÈṲ̂ӷ cells” Proc Staff Meet Mayo Clin 1948; 23: 25. ʈÛÊÔÏÈ›‰È·. ∏ ·ÚÔ˘Û›· ∞º∞ ÛÙÔÓ ÔÚfi, Û˘ÓÔ- 3. Friou GJ. Clinical application of Lupus serum-nucleoprotein ‰Â˘fiÌÂÓË ·fi ·ÚÙËÚȷΤ˜ ‹ ÊÏ‚ÈΤ˜ ıÚÔÌ‚ÒÛÂȘ ‹ reaction using the fluorescent antibody technique. J Clin Invest 1957, 36: 890-7. ·ÓÂÈÏËÌ̤Ó˜ ·˘ÙfiÌ·Ù˜ ·Ô‚ÔϤ˜, Û˘ÓÈÛÙ¿ ¤Ó· 4. Harmon CE. Antinuclear antibodies in autoimmun disease. ·˘ÙÔ¿ÓÔÛÔ ÎÏÈÓÈÎfi Û‡Ó‰ÚÔÌÔ Ô˘ ÔÓÔÌ¿˙ÂÙ·È «∞ÓÙÈ- Significance and pathogenicity. Symposium of Clinical Im- ʈÛÊÔÏÈȉÈÎfi ™‡Ó‰ÚÔÌÔ»28,29. munology 1. Medical Clinics of North America 1985; 48 ∂ÚÁ·ÛÙËÚȷ΋ ÚÔÛ¤ÁÁÈÛË ·˘ÙÔ¿ÓÔÛˆÓ ÚÂ˘Ì·ÙÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ
69(3): 547-563. with systemic vasculitis and idiopathic necrotizing and 5. Fritzler MJ. Immunofluororescent antinuclear antibody test: crecentic glomerulonephritis. N Engl J Med 1988; 318: In Manual of Clinical Laboratory Immunology, fourth 1651-7. edition American Society for Microbiology, Washington 22. Jennette JC, Falk RJ. Antineutrophil cytoplasmic and associa- DC, 1992; 724-9. ted diseases: a review. Am J Kidney Dis 1990; 15: 517-29. 6. Tan EM, Feltkamp TE, Smolen JS, et al. Range of antinuclear 23. Gross WL, Schmitt WH, Csemok E. ANCA and associa- antibodies in “healthy” individuals. Arthritis Rheum. ted diseases: immunodiagnostic and pathogenetic as- 1997; 40(9): 1601-11. pects. Clin Exp Immunol 1993; 91: 1-12. 7. Reeves WH, Satoh M, Jingson W, Chou C-H, Ajmani AK. 24. Halbwachs-Mecarelli L, Nubaum P, Noel LH, et al. Anti- Antibodies to DNA, DNA-binding proteins and histo- neutrophil cytoplasmic antibodies (ANCA) directed a- nes. Reum Dis Clin North Am 1994; 20 (1): 1-28. gainst cathepsin G in ulcera colitis, Chron’s disease and 8. Felsenfeld G. Cromatin as an essential part of the transcri- primary sclerosing cholangitis. Clin Exp Immunol 1992; ptional mechanism. Nature 1992; 355(6357): 219-24. 90: 79-84. 25. Schellekens GA, de Jong BA, van den Hoogen FH, van de 9. Peng SL, Hardin JA, Craft J. Antinuclear antibodies. In Kelley Putte LB, van Venrooij WJ. Citrulline is an essential con- WN, Harris ED, Ruddy S, Sledge CB (eds): Textbook of stituent of antigenic determinants recognized by rheu- Reumatology 5th ed. Philadelphia, WB, Saunders 1995; matoid arthritis-specific autoantibodies. J Clin Invest. 250-266. 1998; 101(1): 273-81. 10. Fritzler MJ, Kinsella D, Garbutt E. The CREST syndrome: A 26. Schellekens GA, Visser H, de Jong BAW, van den Hoogen distinct serologic entity with anticentromere antibodies. FH, Hazes JM, Breedveld FC, van Venrooij WJ. The Am J Med. 1980; 69: 520-6. diagnostic properties of rheumatoid arthritis antibodies 11. Moroi V, Peebles C, Fritzler M, Steigerwald J, Tan EM. Au- recognizing a cyclic citrullinated peptide. Arhtritis Rhe- toantibody to centromere (kinetochore) in scleroderma um. 2000; 43: 155-64. sera. Proc Natl Acad Sci USA 1980; 77: 1627-31. 27. Coenen D, Verschueren P, Westhovens R and Bossuyt X. 12. Toubi E, Shoenfeld Y. Clinical and biological aspects of Technical and Diagnostic Performance of 6 Assays for anti-ribosomal protein autoantibodies. Autoimmun Rev. the Measurement of Citrullinated Protein/Peptide An- 2007; 6(3): 119-25. tibodies in the Diagnosis of Rheumatoid Arthritis. Clin 13. Snowden N, Hay E, Holt PJ, Bernstein R. Clinical course of Chemistry 2007; 53: 498-504. patients with anti-RNP antibodies J Rheumatol. 1993; 20: 28. Hughes GRV. Thrombosis, abortion, cerebral disease and 1256-8. lupus anticoagulant. BMJ 1983; 287: 1088-9. 14. Moder KG. Use and interpretation of rheumatologic tests: 29. Asherson RA, Cervera R. Antiphospholipid Syndrome. In a guide for clinicians. Mayo Clin Proc 1996; 71: 391-396. Kelley WN, Harris ED, Ruddy S, Sledge CB (eds): Text- 15. Harley JB, Scofield RH, Reichlin M. Anti-Ro in Sjögren’s book of Reumatology 5th ed. Philadelphia, WB, Sa- syndrome and systemic lupus erythematosus. Rheum unders 1995; 1057-64. Dis Clin North Am 1992; 18: 337-358. 30. Galli M, Finazzi G, Bevers ∂ª, Barbui Δ. Caolin clotting time 16. St. Clair EW. Anti-La antibodies. Rheum Dis Clin North and dilute Russell’s viper venom time distinguish bet- Am 1992;18: 359-376. ween prothrombin-dependent and ‚2-glycoprotein I- dependent antiphospholipid antibodies. Blood 1995; 86 17. Reiter G, Steen V, Penning C. Correlates between autoan- (2): 617-23. tibodies to nucleolar antigens as clinical features in pa- tients with systemic sclerosis (scleroderma). Arthritis 31. Giannakopoulos μ, Passam F, Ioannou Y, Krilis SA. How we Rheum 1988; 31: 525-532. diagnose the antiphospholipid syndrome. Blood 2009; 113 (5): 985-94. 18. Tan EM. Antinuclear antibodies: Diagnostic markers for autoimmune diseases and probes for cell biology. Adv 32. Loizou, S, McCrae, JD, Ridge, AC, et al. Measurement of Immunol 1989; 44: 93-151. anti-cardiolipin antibodies by an enzyme-linked immu- nsorobent assay (ELISA): standardization and quantita- 19. Wilson RM, Sanders RD. Immunodiffusion assays for anti- tion of results. Clin. Exp. Immunol. 1985; 62: 738-45. bodies to small nuclear ribonucleoproteins and other cellular antigens: In Manual of Clinical Laboratory Immu- 33. Wong RC. Consensus guidelines for anticardiolipin antibody testing. Thromb Res. 2004; 114: 559-71. nology, 4th ed. American Society for Microbiology, Washington DC, 1992; 741. 34. Assi L. K, Taylor D, Vogt F. R, Hughes RG. The standardi- sation of antiphospholipid syndrome assays. 2008; Cli- 20. Nölle B, Specks U, Lüdemann G, Rohrbach M, Deremee online.com. R, Gross WL. Anticytoplasmic autoantibodies. Ann Int Med 1989; 111(1): 28-40. 21. Falk RJ, Jennette JC. Anti-neutrophil cytoplasmic autoanti- ∞ÏÏËÏÔÁÚ·Ê›·: bodies with specificity for myeloperoxidase in patients E-mail: [email protected] ∞Ó·ÛÎfiËÛË
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Δ· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· Á›ÓÂÙ·È ÏfiÁÔ˜ ÁÈ· ÙËÓ ·˘ÙÔÊÏÂÁÌÔÓ‹, ‰ËÏ·‰‹ ÙÔ ·ÔÙ¤ÏÂÛÌ· Ì›·˜ ·Ó·ÈÙÈÔÏfiÁËÙ˘ ‰È¤ÁÂÚÛ˘ Ù˘ ÌË ÂȉÈ΋˜ ·ÓÔÛ›·˜ ·Ô˘Û›· ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ Î·È ·˘ÙÔ·ÓÙȉڷÛÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ. √ ÎÏÈÓÈÎfi˜ ‰È·¯ˆÚÈÛÌfi˜ Û ‰È·ÎÚÈÙ¤˜ ÔÓÙfiÙËÙ˜ Î·È Ë ÌÔÚÈ·- ΋ Ù·˘ÙÔÔ›ËÛË Ù˘ ÁÂÓÂÙÈ΋˜ ‚Ï¿‚˘ Û οı ̛· ·fi ·˘Ù¤˜ Ô‰‹ÁËÛ ÛÙË ‰È¢ÎÚ›ÓÈÛË ÙˆÓ ˘ÔΛÌÂÓˆÓ ÌÔÓÔ·ÙÈÒÓ. ∏ ·ÚÔ‡Û· ·Ó·ÛÎfiËÛË ·ÔÛÎÔ› ÛÙÔ Ó· ·ÚÔ˘ÛÈ¿ÛÂÈ ÂÓ Û˘ÓÙÔÌ›· ÙȘ ¤ˆ˜ ÙÒÚ· ÁÓÒÛÂȘ ¿Óˆ ÛÙË ÌÔÚȷ΋ ·ıÔÏÔÁ›· Î·È ÙËÓ ÎÏÈÓÈ΋ Ú¿- ÍË Î·ıÒ˜ Î·È Ó· ·ÚÔ˘ÛÈ¿ÛÂÈ Ù· ÛËÌ·ÓÙÈÎfiÙÂÚ· ¤ˆ˜ ÙÒÚ· ÂÚˆÙ‹Ì·Ù· Ô˘ ΢ÚÈ·Ú¯Ô‡Ó ÛÙËÓ ÙÚ¤¯Ô˘Û· ¤Ú¢ӷ ÙÔ˘ ‰›Ô˘.
§¤ÍÂȘ-ÎÏÂȉȿ: ∞˘ÙÔÊÏÂÁÌÔÓ‹, oÈÎÔÁÂÓ‹˜ ÌÂÛÔÁÂÈ·Îfi˜ ˘ÚÂÙfi˜, ÈÓÙÂÚÏ¢ΛÓË-1‚.
√ÚÈÛÌfi˜ Î·È Ù·ÍÈÓfiÌËÛË ÛÈ¿˙Ô˘Ó ¤Ó·Ó ÎÔÈÓfi ˘Ú‹Ó· ÎÏÈÓÈÎÒÓ ÂΉËÏÒÛÂˆÓ Î·È ¤¯Ô˘Ó ˆ˜ › ÙÔ Ï›ÛÙÔÓ ¯·Ú·ÎÙËÚÈÛÙ› ÌÔÚȷο, √ fiÚÔ˜ «·˘ÙÔÊÏÂÁÌÔÓÒ‰Ë ÓÔÛ‹Ì·Ù·» ·Ó·Ê¤ÚÂÙ·È Û˘Ì‚¿ÏÏÔÓÙ·˜ ¤ÙÛÈ ÛÙË ÌÂϤÙË Ù˘ ÌÔÚȷ΋˜ ·ıÔ- Û ̛· ÔÌ¿‰· ·ÛıÂÓÂÈÒÓ Ô˘ ÔÊ›ÏÔÓÙ·È Û ‰È·Ù·Ú·- ÏÔÁ›·˜ Ù˘ ·˘ÙÔÊÏÂÁÌÔÓÒ‰Ô˘˜ ‰È·‰Èηۛ·˜. ™Ù· Û‡Ó- ¯‹ Ù˘ ÌË ÂȉÈ΋˜ ·ÓÔÛ›·˜ Î·È ¯·Ú·ÎÙËÚ›˙ÔÓÙ·È ·fi ‰ÚÔÌ· ·˘Ù¿ Û˘ÁηٷϤÁÔÓÙ·È ÓÔÛ‹Ì·Ù· ÂÚÈÛÛfiÙÂ- ÂÂÈÛfi‰È· Û˘ÛÙËÌ·ÙÈ΋˜ ÊÏÂÁÌÔÓÒ‰Ô˘˜ ·ÓÙ›‰Ú·Û˘, ÚÔ ÁÓˆÛÙ¿ Î·È Û¯ÂÙÈο Û˘¯Ó¿ ÛÙËÓ ∂ÏÏ¿‰·, fiˆ˜ Ô Ù· ÔÔ›· ÂÈÛ‚¿ÏÏÔ˘Ó Î·È ˘Ê›ÂÓÙ·È Î·Ù¿ ÙÚfiÔ ·ÚÔ- ÔÈÎÔÁÂÓ‹˜ ÌÂÛÔÁÂÈ·Îfi˜ ˘ÚÂÙfi˜ (FMF-Familial medi- ÂȉÔÔ›ËÙÔ Î·È Ê·ÈÓÔÌÂÓÈο ·ÓÂÍ‹ÁËÙÔ. ™ÙË ÊÏÂÁÌÔ- terranean fever), ·ÏÏ¿ Î·È Î¿ÔÈ· Û·ÓÈfiÙÂÚ·, fiˆ˜: Ó‹ ÎÈÓËÙÔÔÈÔ‡ÓÙ·È Ô˘‰ÂÙÂÚfiÊÈÏ· Î·È Ì·ÎÚÔÊ¿Á·, Ù· ÔÔ›· Ô‰ËÁÔ‡Ó Û ÈÛÙÈ΋ ‚Ï¿‚Ë. ∫‡ÚÈ· ÚÔ¸fiıÂÛË – ÙÔ ÂÚÈÔ‰ÈÎfi Û‡Ó‰ÚÔÌÔ Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ÙÔÓ ÁÈ· ÙË ıÂÒÚËÛË Ù˘ ·˘ÙÔÊÏÂÁÌÔÓ‹˜ Ï·Ì‚¿ÓÂÙ·È Ë ˘Ô‰Ô¯¤· ÙÔ˘ TNF (TRAPS–TNF–receptor associa- ·Ô˘Û›· ÂӉ›ÍÂˆÓ Û˘ÌÌÂÙÔ¯‹˜ ·ÓÙÈÁÔÓÔÂȉÈÎÒÓ Δ ted periodic syndrome), ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ ‹ ÛËÌ·ÓÙÈ΋˜ ·Ú·ÁˆÁ‹˜ ·˘ÙÔ·ÓÙÈ- – ÙÔ ÂÚÈÔ‰ÈÎfi Û‡Ó‰ÚÔÌÔ Ô˘ Û¯ÂÙ›˙ÂÙ·È ÌÂ ÛˆÌ¿ÙˆÓ ÛÙËÓ ·ıÔÏÔÁ›· ÙÔ˘ Ê·ÈÓÔ̤ÓÔ˘1. ·Ó¿ÚÎÂÈ· Ù˘ Ì‚·ÏÔÓÈ΋˜ ÎÈÓ¿Û˘ (MAPS–Meva- ∏ ·˘ÙÔÊÏÂÁÌÔÓ‹ ÌÔÚ› Ó· Â›Ó·È ÂΉ‹ÏˆÛË Ô˘ lonate kinase deficiency associated periodic syndro- ÂÚÈÔÚ›˙ÂÙ·È Û ¤Ó·Ó ÈÛÙfi ‹ Û‡ÛÙËÌ· ‹, Û˘ÓËı¤ÛÙÂ- me), Ì ÙȘ ‰‡Ô Û˘ÓÈÛÙÒÛ˜ ÙÔ˘: ·) ÙÔ ÂÚÈÔ‰ÈÎfi Ú·, Ó· Ù˘Á¯¿ÓÂÈ ÔÏ˘Û˘ÛÙËÌ·ÙÈ΋˜ ηٷÓÔÌ‹˜. Δ· Û‡Ó‰ÚÔÌÔ Ô˘ Û˘Óԉ‡ÂÙ·È ·fi ˘ÂÚÁ·ÌÌ·ÛÊ·ÈÚÈ- ÎÏËÚÔÓÔÌÔ‡ÌÂÓ· ˘ÔÙÚÔÈ¿˙ÔÓÙ· Â̇ÚÂÙ· Û‡Ó- Ó·ÈÌ›· D (HIDS–Hyperimmunoglobulinaemia D with ‰ÚÔÌ· (hereditary recurrent fever syndromes) ‹ Â- periodic fever syndrome) Î·È ‚) ÙË Ì‚·ÏÔÓÈ΋ Ô͢- ÚÈÔ‰Èο Û‡Ó‰ÚÔÌ· ıˆÚÔ‡ÓÙ·È ˆ˜ ÙÔ ÚˆÙfiÙ˘Ô Ô˘Ú›· (MA–Mevalonate aciduria) Î·È ÎÏÈÓÈÎfi ÌÔÓÙ¤ÏÔ Ù˘ ·˘ÙÔÊÏÂÁÌÔÓ‹˜, ηıÒ˜ ·ÚÔ˘- – ÙÔ ÎÚ˘Ô·ÁÒÌÂÓÔ ·˘ÙÔÊÏÂÁÌÔÓ҉˜ Û‡Ó- 50 ™˘ÛÙËÌ·ÙÈο ·˘ÙÔÊÏÂÁÌÔÓÒ‰Ë ÓÔÛ‹Ì·Ù·
‰ÚÔÌÔ (CAPS – Cold induced autoinflammatory syn- Û˘ÌϤÁÌ·ÙÔ˜ ÈÛÙÔÛ˘Ì‚·ÙfiÙËÙ·˜ Ô˘ ·Ú·ÙËÚÂ›Ù·È drome 1 [CIAS1] associated periodic syndrome) Ì Û ÔÏϤ˜ ÎÏÈÓÈΤ˜ ÔÓÙfiÙËÙ˜ Ì ·˘ÙÔηÙ¢ı˘ÓfiÌÂÓË ÙȘ ÙÚÂȘ Û˘ÓÈÛÙÒÛ˜ ÙÔ˘: ·) ™‡Ó‰ÚÔÌÔ Muckle-Wells ·ÓÔÛÔÏÔÁÈ΋ ‰Ú·ÛÙËÚÈfiÙËÙ·. ™Â ·¿ÓÙËÛË Û ·˘Ù‹Ó (MWS), ‚) √ÈÎÔÁÂÓ‹˜ ÎÚ˘Ô·ÁÒÌÂÓË Ô˘ÚÙÈοÚÈ· ÙËÓ ·Ó·ÎÔÏÔ˘ı›·, οو ·fi ÙËÓ ÔÔ›· ›¯Â ˆÚÈÌ¿ÛÂÈ (FCU – Familial cold urticaria)/√ÈÎÔÁÂÓ¤˜ ÎÚ˘Ô·- Î·È Ë È‰¤· Ù˘ ·˘ÙÔÊÏÂÁÌÔÓ‹˜, Ë Matzinger ·Ó¤Ù˘Í ÁÒÌÂÓÔ ·˘ÙÔÊÏÂÁÌÔÓ҉˜ Û‡Ó‰ÚÔÌÔ (FCAS – Fami- ÙË ıˆڛ· Ù˘ ·Ó›¯Ó¢Û˘ ÛËÌ¿ÙˆÓ ÎÈÓ‰‡ÓÔ˘ (dan- lial cold autoinflammatory syndrome) Î·È Á) ÃÚfiÓÈÔ ger signal theory), Û‡Ìʈӷ Ì ÙËÓ ÔÔ›· Ô ÔÚÁ·ÓÈ- Ó¢ÚÔ-‰ÂÚÌ·ÙÔ-·ÚıÚÈÎfi Û‡Ó‰ÚÔÌÔ ‚ÚÂÊÒÓ (CIN- ÛÌfi˜ ‰ÂÓ ÂӉȷʤÚÂÙ·È ÙfiÛÔ Ôχ ÁÈ· ÙË ‰È¿ÎÚÈÛË CA – Chronic infantile neurological cutaneous arti- ÌÂٷ͇ ›‰ÈÔ˘ Î·È ÌË ›‰ÈÔ˘, ·ÏÏ¿ ·ÓȯÓ‡ÂÈ Î·È ·ÍÈÔÔÈ- cular syndrome)/™‡Ó‰ÚÔÌÔ ÔÏ˘Û˘ÛÙËÌ·ÙÈ΋˜ ÊÏÂÁ- › Û‹Ì·Ù· Ô˘ ÚÔˆÓ›˙ÔÓÙ·È Î›Ó‰˘ÓÔ, ÚÔÂÚ¯fiÌÂÓ· ÌÔÓÒ‰Ô˘˜ ·¿ÓÙËÛ˘ ÓÂÔÁÓÒÓ (NOMID – Neonatal ›Ù ·fi ·ıÔÁfiÓ·, ΢ڛˆ˜ ‚·ÎÙ‹ÚÈ· (Â͈ÁÂÓ‹ Û‹- onset multisystem inflammatory disease). Ì·Ù·), ›Ù ·fi ηÙÂÛÙÚ·Ì̤ÓÔ˘˜ ÈÛÙÔ‡˜ (ÂÓ‰ÔÁÂÓ‹ ∂ÎÙfi˜ ·fi Ù· ÎÏËÚÔÓÔÌÔ‡ÌÂÓ· ˘ÔÙÚÔÈ¿˙ÔÓÙ· Û‹Ì·Ù·). ¶·ÚfiÏ· ·˘Ù¿ Î·È ÙÔ ÌÔÓÙ¤ÏÔ Ù˘ Matzinger, Â̇ÚÂÙ· Û‡Ó‰ÚÔÌ·, ÛÙ· ·˘ÙÔÊÏÂÁÌÔÓÒ‰Ë ÓÔÛ‹Ì·- ÂÓÒ ÂÍËÁ› ı·˘Ì¿ÛÈ· ÙËÓ ÎÏÈÓÈ΋ ÂÈÎfiÓ· Ù˘ ·˘ÙÔ- Ù· Û˘ÌÂÚÈÏ·Ì‚¿ÓÔÓÙ·È Î·È ·Ûı¤ÓÂȘ Ô˘ ‰ÂÓÓ ¯·- ÊÏÂÁÌÔÓ‹˜, ¯ˆÏ·›ÓÂÈ ÛÙËÓ ÂÚÈÁÚ·Ê‹ ÙˆÓ ·˘ÙÔ¿ÓÔ- Ú·ÎÙËÚ›˙ÔÓÙ·È ·fi Â̇ÚÂÙ· ÂÂÈÛfi‰È·, ·ÏÏ¿ ÔÈΛ- ÛˆÓ ÔÓÙÔًوÓ3. Ϙ Î·È Û ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ Ê·ÈÓÔÌÂÓÈο ·Û‡Ó- ∞ÎÔÏÔ˘ıÒÓÙ·˜ ÙË ÏÔÁÈ΋ fiÙÈ Î·Ó¤Ó· ·fi Ù· ‰‡Ô ‰ÂÙ˜ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ. ™ÙËÓ ÔÌ¿‰· ·˘Ù‹ ·Ó‹ÎÔ˘Ó ÌÔÓ٤Ϸ ‰ÂÓ Î·Ï‡ÙÂÈ ÙÔ Û‡ÓÔÏÔ ÙˆÓ ·ÓÔÛÔÏÔÁÈÎÒÓ ÙÔ Û‡Ó‰ÚÔÌÔ Blau, ÙÔ Û‡Ó‰ÚÔÌÔ PAPA, ÙÔ Û‡Ó‰ÚÔ- ‰È·Ù·Ú·¯ÒÓ Ô˘ ÂΉËÏÒÓÔÓÙ·È Ì ·˘ÙfiÓÔÌË, ÌË Î·- ÌÔ Majeed, Ë ¯ÚfiÓÈ· ˘ÔÙÚÔÈ¿˙Ô˘Û· ÔÏ˘ÂÛÙȷ΋ Ù¢ı˘ÓfiÌÂÓË ·ÓÔÛȷ΋ ·¿ÓÙËÛË, Ô McDermott ‰È·- ÔÛÙÂÔÌ˘ÂÏ›Ùȉ· (CRMO – chronic recurrent multifo- Ù‡ˆÛ ÙËÓ ˘fiıÂÛË ·Ó Î·È Î·Ù¿ fiÛÔ ÔÚÈṲ̂ӷ ÓÔ- cal ostemyelitis) Î·È ¿ÏÏ·. Û‹Ì·Ù· Ô˘ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ·˘ÙfiÌ·ÙË ÊÏÂÁÌÔÓÒ‰Ë √ ηٿÏÔÁÔ˜ ÙˆÓ ÓfiÛˆÓ Ì ·˘ÙÔÊÏÂÁÌÔÓÒ‰ÂȘ ·¿ÓÙËÛË Î·È Ô˘ ‰ÂÓ ÌÔÚÔ‡Ó Ó· Î·Ï˘ÊıÔ‡Ó Ï‹- Û˘ÓÈÛÙÒÛ˜ (ˆ˜ ·ÚȘ ‹ ‰Â˘ÙÂÚ‡ԢÛ˜ ÂΉËÏÒ- Úˆ˜ ·fi ÙËÓ ·Ú·‰ÔÛȷο ·Ô‰ÂÎÙ‹ ¢ڇÙÂÚË ¤Ó- ÛÂȘ) ÌÂÁ·ÏÒÓÂÈ ÔÏÔ¤Ó· Î·È ÂÚÈÛÛfiÙÂÚÔ, fiÛÔ ÈÔ ÓÔÈ· Ù˘ ·˘ÙÔ·ÓÔÛ›·˜, fiˆ˜, .¯., ÙÔ Û‡Ó‰ÚÔÌÔ Beh- ηٷÓÔËÙ‹ Á›ÓÂÙ·È Ë ÌÔÚȷ΋ ·ıÔÏÔÁ›· Ù˘ ·˘ÙÔ- cet, ÂÚÈÏ·Ì‚¿ÓÔ˘Ó Ù·˘Ùfi¯ÚÔÓ· Î·È Û˘ÓÈÛÙÒÛ· ·˘- ÊÏÂÁÌÔÓ‹˜. π‰È·›ÙÂÚ· ÛËÌ·ÓÙÈ΋ ıˆÚÂ›Ù·È Ë ÂÓۈ̿- ÙÔÊÏÂÁÌÔÓ‹˜. ™‡Ìʈӷ Ì ÙË ıˆڛ· ÙÔ˘ McDer- ÙˆÛË ÛÙȘ Ù¿ÍÂȘ ÙˆÓ ·˘ÙÔÊÏÂÁÌÔÓˆ‰ÒÓ ÓfiÛˆÓ mott, Ë ·˘ÙÔÊÏÂÁÌÔÓ‹ Î·È Ë ·˘ÙÔ·ÓÔÛ›· ·ÔÙÂÏÔ‡Ó ·ÛıÂÓÂÈÒÓ Ô˘ ÚÔηÏÔ‡ÓÙ·È ·fi ÌË Î˘ÙÙ·ÚÈο ÛÙÔÈ- ‰‡Ô ·ÎÚ·›Ô˘˜ fiÏÔ˘˜ ‰È·Ù·Ú·¯‹˜ ÙÔ˘ ·ÓÔÛÔÔÈËÙÈ- ¯Â›· Ô˘ Á›ÓÔÓÙ·È ·ÓÙÈÏËÙ¿ ˆ˜ «Û‹Ì·Ù· ÎÈÓ‰‡ÓÔ˘», ÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ Ô˘ ÂÎÊÚ¿˙ÔÓÙ·È Û¿ÓÈ· ÛÙËÓ Î·- fiˆ˜ ÔÈ ÎÚ˘ÛÙ·ÏÏÔÁÂÓ›˜ ·ÚıÚ›Ùȉ˜ (Ô˘ÚÈ΋ Î·È „¢‰ÔÔ˘ÚÈ΋) Î·È Ë ÛÈϛΈÛË. ∂ÈϤÔÓ, ÓÔÛ‹Ì·Ù· Ì ı·ÚfiÙËÙ· Ô˘ ÂÈÙ¿ÛÛÔ˘Ó ÔÈ ÛËÌÂÚÈÓÔ› ÔÚÈÛÌÔ› ·‰È¢ÎÚ›ÓÈÛÙË ·ıÔÏÔÁ›·, fiˆ˜ Ë ÓfiÛÔ˜ Crohn, ·Ô- ÙÔ˘˜. ∂ÎÙfi˜ ÏÔÈfiÓ ·fi ÙȘ Âη٤ڈıÂÓ ÎÏÈÓÈο ‰È·- ‰ÂÈÎÓ‡ÂÙ·È fiÙÈ ÂÓ Ì¤ÚÂÈ ÔÊ›ÏÔÓÙ·È Û ·˘ÙÔÊÏÂÁÌÔÓ‹. ÎÚÈÙ¤˜ ÌÔÚʤ˜ ÙÔ˘˜, Ô˘ ·ÓÙÈηÙÔÙÚ›˙Ô˘Ó Û˘ÁÎÂÎÚÈ- ™‡Ìʈӷ Ì ·˘Ù‹Ó ÙË ÏÔÁÈ΋, ¤Ó·˜ ˘ÂÚ¢·›ÛıËÙÔ˜ ̤Ó˜ ÁÔÓȉȷΤ˜ ‚Ï¿‚˜ (‚Ϥ ÁÈ· ÙËÓ ÂÚ›ÙˆÛË Ì˯·ÓÈÛÌfi˜ ·Ó›¯Ó¢Û˘ ÛËÌ¿ÙˆÓ Ô‰ËÁ› Û ‰˘Û·Ó¿- Ù˘ ·˘ÙÔ·ÓÔÛ›·˜ ÙÔ ·˘ÙÔ¿ÓÔÛÔ ÔÏ˘ÂÓ‰ÔÎÚÈÓÈÎfi ÏÔÁ· ¤ÓÙÔÓ˜ ÊÏÂÁÌÔÓÒ‰ÂȘ ·ÓÙȉڿÛÂȘ, ˆ˜ ·¿ÓÙË- Û‡Ó‰ÚÔÌÔ Î·È ÙÔ ·˘ÙÔ¿ÓÔÛÔ ÏÂÌÊÔ¸ÂÚÏ·ÛÙÈÎfi ÛË ·ÎfiÌË Î·È Û ÂÏ¿ÛÛÔÓÔ˜ ÛËÌ·Û›·˜ ÌÈÎÚԂȷο ΢- Û‡Ó‰ÚÔÌÔ, ÁÈ· ÙË ‰Â ÂÚ›ÙˆÛË Ù˘ ·˘ÙÔÊÏÂÁÌÔÓ‹˜ Ú›ˆ˜ ·ÓÙÈÁÔÓÈο ÂÚÂı›ÛÌ·Ù·. Yfi ÙÔ Ú›ÛÌ· ·˘Ùfi Ì›· fiÏ· Ù· ÂÚÈÔ‰Èο Û‡Ó‰ÚÔÌ· ÏËÓ ÙÔ˘ PFAPA – Â- ÌÂÁ¿ÏË ÔÈÎÈÏ›· Ê·ÈÓÔÌÂÓÈο ·Û‡Ó‰ÂÙˆÓ ÌÂٷ͇ ÙÔ˘˜ ÚÈÔ‰ÈÎfi Â̇ÚÂÙÔ Û‡Ó‰ÚÔÌÔ Ì ˘Ò‰Ë Ê·Ú˘ÁÁ›Ùȉ· ÎÏÈÓÈÎÒÓ ÔÓÙÔÙ‹ÙˆÓ (.¯., ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ ȉÈÔ- Î·È ·‰ÂÓÔ¿ıÂÈ·), fiϘ ÔÈ ·ÓÔÛÔÏÔÁÈΤ˜ ‰È·Ù·Ú·¯¤˜ ·ıÔ‡˜ ·ÚÙËÚȷ΋˜ ˘¤ÚÙ·Û˘ ‹ ۷ί·ÚÒ‰Ô˘˜ ‰È·- ÌÔÚÔ‡Ó Ó· Ù·ÍÈÓÔÌËıÔ‡Ó Î¿Ô˘ ÂӉȿÌÂÛ·, ÂÚÈ- ‚‹ÙË Ù‡Ô˘ ππ) ÂÓ‰¤¯ÂÙ·È Ó· ÂÓ¤¯Ô˘Ó ·˘ÙÔÊÏÂÁÌÔÓÒ- Ï·Ì‚¿ÓÔÓÙ·˜ ÏÈÁfiÙÂÚÔ ‹ ÂÚÈÛÛfiÙÂÚÔ ÛÙÔȯ›· ·˘- ‰ÂȘ Û˘ÓÈÛÙÒÛ˜2. ÙÔÊÏÂÁÌÔÓ‹˜ ‹ ·˘ÙÔ·ÓÔÛ›·˜. ™ÙËÓ Ù·ÍÈÓfiÌËÛË ·˘Ù‹ ª¤¯ÚÈ ÚÔ ÂÙÒÓ ˘‹Ú¯Â Ë Ù¿ÛË Ó· ‰ÈÂÚÂ˘Ó¿Ù·È ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È, ˆ˜ ÂӉȿÌÂÛ˜ ÎÏÈÓÈΤ˜ ÔÓÙfiÙËÙ˜, οı ·˘ÙfiÓÔÌË, ÌË Û˘Ó‰ÂfiÌÂÓË Ì ۯ¤ÛË ·ÈÙ›Ô˘-·È- ÔÏ˘ÁÔÓȉȷÎÒ˜ ηıÔÚÈ˙fiÌÂÓ˜ ÓfiÛÔÈ Ì ˘ÂÚÔ¯‹ ÙÈ·ÙÔ‡ ·ÓÔÛÔÏÔÁÈ΋ ‰Ú¿ÛË, ˘fi ÙÔ Ú›ÛÌ· Ù˘ ·˘- ¿ÏÏÔÙ Ù˘ ·˘Ù·ÓÔÛ›·˜ (.¯., Û˘ÛÙËÌ·ÙÈÎfi˜ ÂÚ˘ıËÌ·- ÙÔ·ÓÔÛ›·˜. ¶·ÚfiÏ· ·˘Ù¿, Ë ıˆڛ· Ù˘ ‰È¿ÎÚÈÛ˘ Ù҉˘ χÎÔ˜, ÚÂ˘Ì·ÙÔÂȉ‹˜ ·ÚıÚ›Ùȉ·, ·˘ÙÔ¿ÓÔÛË ÙÔ˘ ›‰ÈÔ˘ ·fi ÙÔ ÌË ›‰ÈÔ (self/non-self distinction ı˘ÚÂÔÂȉ›Ùȉ·, ۷ί·Ú҉˘ ‰È·‚‹Ù˘ Ù‡Ô˘ 1) Î·È theory) ‰ÂÓ ÌÔÚ› Ó· ÂÍËÁ‹ÛÂÈ Â˘Ú‹Ì·Ù· fiˆ˜ Ë ¿ÏÏÔÙ Ù˘ ·˘ÙÔÊÏÂÁÌÔÓ‹˜ (.¯., ÓfiÛÔ˜ Crohn, ÂÏ- ¤ÏÏÂÈ„Ë Û˘Û¯¤ÙÈÛ˘ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ Î·È Ì›˙ÔÓÔ˜ Î҉˘ ÎÔÏ›Ùȉ·, ÔÛÙÂÔ·ÚıÚ›Ùȉ·, Ô˘ÚÈ΋ ·ÚıÚ›Ùȉ·)4. °. ªËÙÚÔ‡Ï˘, μ. ¶··‰fiÔ˘ÏÔ˜ 51
∫ÏËÚÔÓÔÌÔ‡ÌÂÓ· ˘ÔÙÚÔÈ¿˙ÔÓÙ· ÓË ¤Ó·ÚÍË ÙˆÓ Û˘ÌÙˆÌ¿ÙˆÓ (ÌÂÙ¿ Ù· 30 ¤ÙË). Â̇ÚÂÙ· Û‡Ó‰ÚÔÌ·: Û˘ÁÎÚÈÙÈ΋ ·- √È ÎÚ›ÛÂȘ ˘ÚÔ‰ÔÙÔ‡ÓÙ·È ·fi ¤ÓÙÔÓË Ê˘ÛÈ΋ ÚÔ˘Û›·ÛË Ù˘ ÎÏÈÓÈ΋˜ ÂÈÎfiÓ·˜ ‰Ú·ÛÙËÚÈfiÙËÙ·, Û˘Ó·ÈÛıËÌ·ÙÈÎfi stress, ÏÔÈÌÒÍÂȘ, ¤Î- ıÂÛË ÛÙÔ ÎÚ‡Ô Î·È ¤ÌÌËÓÔ Ú‡ÛË Î·È ÂÚÈÏ·Ì‚¿ÓÔ˘Ó, √ ÎÏÈÓÈÎfi˜ ˘Ú‹Ó·˜ ÙˆÓ ÎÏËÚÔÓÔÌÔ‡ÌÂÓˆÓ ˘ÔÙÚÔ- ÂÎÙfi˜ ÙÔ˘ ˘ÚÂÙÔ‡, ÔÚÔÁÔÓ›Ùȉ˜ (Ì ÙË ÌÔÚÊ‹ ÂÚÈ- È·˙fiÓÙˆÓ Â̇ÚÂÙˆÓ Û˘Ó‰ÚfiÌˆÓ ··ÚÙ›˙ÂÙ·È ·fi ÙÔÓ›Ùȉ·˜, Ï¢ڛÙȉ·˜ ‹ ÂÚÈηډ›Ùȉ·˜), ·ÚıÚ›Ùȉ˜, ÔÚÈṲ̂ӷ ÛÙ·ıÂÚ¿ ÂÌÊ·ÓÈ˙fiÌÂÓ· ¯·Ú·ÎÙËÚÈÛÙÈο, Ì˘·ÏÁ›Â˜, ‰ÂÚÌ·ÙÈΤ˜ ÂΉËÏÒÛÂȘ Î·È ÈÔ Û¿ÓÈ· ÚÔ- ÛÙ· ÔÔ›· ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È: Û‚ÔÏ‹ ¿ÏÏˆÓ ÔÚÁ¿ÓˆÓ (fiگˆÓ, ·ÌÊÈ‚ÏËÛÙÚÔÂÈ- – ∏ ÂÌÊ¿ÓÈÛË Û ·È‰È΋ ËÏÈΛ· ‰Ô‡˜, ÛÏËÓfi˜ ηÈ, fiˆ˜ ˘ÔÛÙËÚ›˙ÂÙ·È ·fi ÔÚÈṲ̂- – √ ‰È·Ï›ˆÓ ¯·Ú·ÎÙ‹Ú·˜ ÙˆÓ Û˘ÌÙˆÌ¿ÙˆÓ ÓÔ˘˜ ÙÔ˘Ï¿¯ÈÛÙÔÓ, ÌËÓ›ÁÁˆÓ). √È ÎÚ›ÛÂȘ ‰È·ÚÎÔ‡Ó ÏÈ- – √È ‚ÈÔÏÔÁÈΤ˜ ÂӉ›ÍÂȘ ÊÏÂÁÌÔÓÒ‰Ô˘˜ ·¿- ÁfiÙÂÚÔ ·fi 3 Ë̤Ú˜ Î·È ÌÔÚÔ‡Ó Ó· ·ӷϷ̂¿- ÓÙËÛ˘ fiˆ˜ Ë ·ÚÔ˘Û›· Ô˘‰ÂÙÂÚÔÊ›ÏˆÓ ÛÙÔ˘˜ ÊÏÂ- ÓÔÓÙ·È, ¯ˆÚ›˜ ȉȷ›ÙÂÚË ÂÚÈÔ‰ÈÎfiÙËÙ·, ÌÂ Û˘¯ÓfiÙËÙ· ÁÌ·›ÓÔÓÙ˜ ÈÛÙÔ‡˜ Î·È Ë ·‡ÍËÛË Ù˘ CRP Ô˘ Î˘Ì·›ÓÂÙ·È ·fi ¿Óˆ ·fi Ì›· ÙÔÓ Ì‹Ó· ¤ˆ˜ Î·È – √ ÔÈÎÔÁÂÓ‹˜ ¯·Ú·ÎÙ‹Ú·˜ οو ·fi Ì›· ÙÔ ¯ÚfiÓÔ. ΔÔ Î·Ù¿ fiÛÔ Ë ·˘ÙÔÊÏÂÁ- – ∏ ·Ì˘ÏÔ›‰ˆÛË ˆ˜ ·ÒÙÂÚË ÂÈÏÔ΋ ÌÔÓ‹ ÂÚÈÔÚ›˙ÂÙ·È ÌfiÓÔ ÛÙȘ ÎÚ›ÛÂȘ ‹ Ì›· ·˘ÍË̤ÓË √È ‰È·ÊÔÚ¤˜ ÙˆÓ ‰È·ÎÚÈÙÒÓ ÔÓÙÔÙ‹ÙˆÓ Ô˘ ·- «··ÓÙËÙÈÎfiÙËÙ·» Û ÂÚÂı›ÛÌ·Ù· Ô˘ Ô‰ËÁ› Û ·ÚÙ›˙Ô˘Ó ÙËÓ ÔÌ¿‰· ÙˆÓ ÎÏËÚÔÓÔÌÔ‡ÌÂÓˆÓ ˘ÔÙÚÔ- ˘ÔÎÏÈÓÈ΋ ·˘ÙÔÊÏÂÁÌÔÓ‹ Û˘ÓÙËÚÂ›Ù·È ‰È·ÚÎÒ˜, Â›Ó·È È·˙fiÓÙˆÓ Â̇ÚÂÙˆÓ Û˘Ó‰ÚfïÓ, ‰ËÏ·‰‹ ÙÔ˘ FMF, ¤Ó· ı¤Ì· Ô˘ ‰ÈÂÚÂ˘Ó¿Ù·È. TRAPS, HIDS Î·È CAPS (MWS, FCU/FCAS, CINCA/ ΔÔ Â̇ÚÂÙÔ Â›Ó·È ‰È·ÚΛ·˜ <3 ËÌÂÚÒÓ, ÎÔÚ˘- NOMID), ·Ú·Ù›ıÂÓÙ·È ÂÚÈÏËÙÈο ÛÙÔÓ ›Ó·Î· 1. ÊÒÓÂÙ·È Û ϛÁ˜ ÒÚ˜ Î·È ÌÔÚ› Ó· ·ÁÁ›ÍÂÈ ÙÔ˘˜ 40Ô C. √ ˘ÚÂÙfi˜ χÂÙ·È ·˘ÙfiÌ·Ù·, ›Û˘ Û ۇÓÙÔÌÔ √ ÔÈÎÔÁÂÓ‹˜ ÌÂÛÔÁÂÈ·Îfi˜ ˘ÚÂÙfi˜ ‰È¿ÛÙËÌ· ÔÏ›ÁˆÓ ˆÚÒÓ, Û˘Ó‹ıˆ˜ ÚÔ Ù˘ Ï‹ÚÔ˘˜ ˆ˜ ÚfiÙ˘Ô ÎÏËÚÔÓÔÌÔ‡ÌÂÓÔ˘ ˘Ô- ·Ô‰ÚÔÌ‹˜ ÙˆÓ ˘ÔÏÔ›ˆÓ ÎÏÈÓÈÎÒÓ ÂΉËÏÒ-ÛˆÓ. ÙÚÔÈ¿˙ÔÓÙÔ˜ ÂÌ˘Ú¤ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ŸÛÔÓ ·ÊÔÚ¿ ÙȘ ÔÚÔÁÔÓ›Ùȉ˜, Ë ÂÚÈÙÔÓ›Ùȉ· – ∏ ∂ÏÏËÓÈ΋ ÂÌÂÈÚ›· ÂΉËÏÒÓÂÙ·È ÛÙÔ 96% ÙˆÓ ÂÚÈÙÒÛÂˆÓ Î·È Î˘ÚÈ·Ú- ¯Â› Û 4 ·fi ÙÔ˘˜ 5 ·ÛıÂÓ›˜. ∫·ıÒ˜ ÚÔÛÔÌÔÈ¿˙ÂÈ O ÔÈÎÔÁÂÓ‹˜ ÌÂÛÔÁÂÈ·Îfi˜ ˘ÚÂÙfi˜ ·ÓȯÓ‡ÂÙ·È Î˘- Ì ÙË ¯ÂÈÚÔ˘ÚÁÈ΋ ÎÔÈÏ›·, ¤Ó· ÔÛÔÛÙfi ÂÚ›Ô˘ 30% Ú›ˆ˜ ÛÙÔ˘˜ ÏËı˘ÛÌÔ‡˜ Ô˘ ¢ڛÛÎÔÓÙ·È ÂÚ› ÙË ÙˆÓ ·ÛıÂÓÒÓ ˘Ô‚¿ÏÏÂÙ·È Û ÛΈÏËÎÔÂȉÂÎÙÔÌ‹, ȉÈ- ªÂÛfiÁÂÈÔ, fiˆ˜ ‰ËÏÒÓÂÈ Î·È ÙÔ fiÓÔÌ¿ ÙÔ˘. ∂ÓÙÔ‡- ·›ÙÂÚ· ÛÙËÓ ÂÚ›Ô‰Ô ÚÔ Ù˘ Û·ÊÔ‡˜ (ÌÔÚȷ΋˜) ÙÔȘ, Ë ÌÂٷΛÓËÛË ÏËı˘ÛÌÒÓ, ȉȷ›ÙÂÚ· ¤ÓÙÔÓÔ Ê·È- ‰È·ÁÓÒÛˆ˜. ∏ Ï¢ڛÙȉ· Â›Ó·È Â›Û˘ Û˘¯Ó‹ (ÂÈÛË- ÓfiÌÂÓÔ ÙˆÓ ÙÂÏÂ˘Ù·›ˆÓ ‰ÂηÂÙÈÒÓ, ¤¯ÂÈ Ô‰ËÁ‹ÛÂÈ Û ̷›ÓÂÙ·È Û 25-80% ÙˆÓ ÂÚÈÙÒÛˆÓ) Î·È ÂÌÊ·Ó›˙Â- Ì›· ÏÈÁfiÙÂÚÔ ÔÚÈÔıÂÙË̤ÓË ÁÂÓÂÙÈ΋ ÂȉËÌÈÔÏÔÁ›· Ù·È Ì ¤ÓÙÔÓÔ ıˆÚ·ÎÈÎfi fiÓÔ Ô˘ ÌÈÌÂ›Ù·È ÔÚÈṲ̂Ó˜ ÙÔ˘ ÓÔÛ‹Ì·ÙÔ˜. ÊÔÚ¤˜ Ó¢ÌÔÓÈ΋ ÂÌ‚ÔÏ‹, ÂÓ›ÔÙ ‰Â ·Ó·Ù‡ÛÛÂÙ·È ¶ÚfiÎÂÈÙ·È ÁÈ· ¤Ó· ÓfiÛËÌ· Ô˘ Û ·Ú·¿Óˆ Î·È ÂÍ›‰ÚˆÌ·. ∏ ÂÚÈηډ›Ùȉ· Â›Ó·È Û¯ÂÙÈο Û¿ÓÈ· ·fi ÙȘ ÌÈÛ¤˜ ÂÚÈÙÒÛÂȘ ¤¯ÂÈ ÍÂÎÈÓ‹ÛÂÈ ‹‰Ë ηٿ ÙË (<1%), ·ÏÏ¿ ÌÔÚ› Ó· ÂÍÂÏȯı› Û ηٿÛÙ·ÛË ·ÂÈ- ‰È¿ÚÎÂÈ· Ù˘ ÚÒÙ˘ ‰ÂηÂÙ›·˜ Ù˘ ˙ˆ‹˜. ªfiÓÔ 4% ÏËÙÈ΋ ÁÈ· ÙË ˙ˆ‹ ÏfiÁˆ Ê·ÈÓÔÌ¤ÓˆÓ Û˘Ì›ÂÛ˘. ÙˆÓ ·ÛıÂÓÒÓ ·Ó·Ì¤ÓÂÙ·È Ó· ÂÌÊ·Ó›˙ÂÈ Î·ı˘ÛÙÂÚË̤- √È ·ÚıÚ›Ùȉ˜ Â›Ó·È ÛÔ‚·Ú¤˜, ·ÈÊÓ›‰È˜, ÎÔÚ˘-
¶›Ó·Î·˜ 1. ¢È·ÊÔÚ¤˜ ÛÙȘ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ÎÏËÚÔÓÔÌÔ‡ÌÂÓˆÓ ˘ÔÙÚÔÈ·˙fiÓÙˆÓ Â̇ÚÂÙˆÓ Û˘Ó‰ÚfïÓ. ∞À= ·˘ÙÔÛˆÌÈ- ΋ ˘ÔÏÂÈfiÌÂÓË, ∞∂= ·˘ÙÔÛˆÌÈ΋ ÂÈÎÚ·ÙÔ‡Û·, ™= Û˘ÌÙÒÌ·Ù·. † ÂÚ˘ÛÈÂÏ·ÙÔÂȉ¤˜ ÂÍ¿ÓıËÌ·, # ÔÈΛϷ Û˘ÌÙÒÌ·Ù·10
FMF TRAPS HIDS CAPS ∫ÏËÚÔÓÔÌÈÎfiÙËÙ· ∞À ∞∂ ∞∂ ∞À °ÂÓÂÙÈ΋ ‚Ï¿‚Ë MEFV TNFRSF1A MVK CIAS1/NALP3 ¢È¿ÚÎÂÈ· ÎÚ›Û˘ <3 Ë̤Ú˜ >7 Ë̤Ú˜ 3-7 Ë̤Ú˜ ÔÈΛÏÏÂÈ ∫ÔÈÏȷο ™. + + + - ∞ÚıÚ›Ùȉ˜ + + + + £ˆÚ·ÎÈο ™. + + + - ¢ÂÚÌ·ÙÈο ™. <40% † ~70% >90% Ô˘ÚÙÈοÚÈ· ‘∞ÏÏ· ™. ÂÚÈÎÔÁ¯ÈÎfi Ô›‰ËÌ· ÏÂÌÊ·‰ÂÓÔ¿ıÂÈ· ÎÒʈÛË, Ô›‰ËÌ· ıËÏ‹˜ ∞Ì˘ÏÔ›‰ˆÛË + + + + 52 ™˘ÛÙËÌ·ÙÈο ·˘ÙÔÊÏÂÁÌÔÓÒ‰Ë ÓÔÛ‹Ì·Ù·
ΤLRs
Σήματα κινδύνου (ΜSU, ATP, PAMPs) NF-κβ
pro-IL-1β Kρυοπυρίνη
Κασπάση
IL-1β ΑSC Πυρίνη
Πρωτεολυτική Επαγωγή
™¯. 1. ™¯ËÌ·ÙÈ΋ ·fi‰ÔÛË Ù˘ Ô‰Ô‡ ‰È¤ÁÂÚÛ˘ ÙÔ˘ ÊÏÂÁÌÔÓÔÛÒÌ·ÙÔ˜ ÎÚ˘Ô˘Ú›Ó˘/ASC Î·È Ù˘ ·Ú·ÁˆÁ‹˜ ÈÓÙÂÚÏ¢ΛÓ˘-1‚.
ÊÒÓÔÓÙ·È Û 24-48 ÒÚ˜, ‰È·ÚÎÔ‡Ó 3-7 Ë̤Ú˜ Î·È ·- ÈÓˆ‰ÔÁfiÓÔ˘. Ô‰Ú¿ÌÔ˘Ó Ï‹Úˆ˜. ∂ÎÙfi˜ ÙˆÓ ÔͤˆÓ ÚÔÛ‚ÔÏÒÓ, ∏ ÌÔÓ·‰È΋ ¤ˆ˜ ÙÒÚ· ÂÁÎÂÎÚÈ̤ÓË Ê·Ú̷΢ÙÈ- Û ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ ·Ú·ÙËÚÂ›Ù·È ¯ÚfiÓÈ· η- ΋ ıÂڷ›· Â›Ó·È Ë ¯ÔÚ‹ÁËÛË ÎÔϯÈΛÓ˘, Ë ÔÔ›· ‰›- Ù·ÛÙÚÔÊÈ΋ ·ÚıÚ›Ùȉ· Ô˘ ·ÊÔÚ¿ Ù· ÈÛ¯›· Î·È Ù· Áfi- ‰ÂÙ·È Â› ÎÚ›ÛÂˆÓ ˆ˜ ÊfiÚÙÈÛË ÌÂ Û˘ÓÔÏÈ΋ ‰fiÛË Ì¤- Ó·Ù· Î·È Û˘ÌÂÚÈÏ·Ì‚¿ÓÂÈ ·ÚÓËÙÈ΋ ˆ˜ ÚÔ˜ ÙÔ ·ÓÙÈ- ¯ÚÈ 6 mg ‹ ̤¯ÚÈ Â›Ù¢Í˘ ‡ÊÂÛ˘ Î·È Â› Û˘ÓÙ‹ÚË- ÁfiÓÔ HLA B27 ÈÂÚÔÏ·ÁÔÓ›Ùȉ·. Û˘ Û ‰fiÛÂȘ Ô˘ Î˘Ì·›ÓÔÓÙ·È ·fi 0,5 ¤ˆ˜ Î·È 3 mg √È Ì˘·ÏÁ›Â˜ (Ô˘ ÂÌÊ·Ó›˙ÔÓÙ·È Û ÔÛÔÛÙfi ËÌÂÚËÛ›ˆ˜. ∏ ÙÈÙÏÔÔ›ËÛË Ù˘ ‰fiÛ˘ ÌÔÚ› Ó· Á›ÓÂÈ 25% ÙˆÓ ·ÛıÂÓÒÓ) Â›Ó·È ÙÚÈÒÓ ‰È·ÎÚÈÙÒÓ Î·ÙËÁÔÚÈÒÓ: Ì ‚‹Ì·Ù· ÙÔ˘ 0,5 mg οı ÙÚ›ÌËÓÔ ¤ˆ˜ ÂÍ¿ÌËÓÔ, ·) ∞˘ÙfiÌ·Ù˜ ηٿ ÙË ‰È¿ÚÎÂÈ· ÙˆÓ ÎÚ›ÛÂˆÓ (8%), ·Ó¿ÏÔÁ· Ì ÙË Û˘¯ÓfiÙËÙ· Î·È ÙË ‚·Ú‡ÙËÙ· ÙˆÓ ÎÚ›- Ô˘ ·ÊÔÚÔ‡Ó Î˘Ú›ˆ˜ Ù· ¿ÎÚ·, ‚) ∂·ÁfiÌÂÓ˜ ·fi ÛˆÓ. ŒÓ· ÔÛÔÛÙfi 5-10% ÙˆÓ ·ÛıÂÓÒÓ Â›Ó·È ÂÍ·Ú- ¿ÛÎËÛË, ·ÎfiÌË Î·È ÛÙÔ ÌÂÛԉȿÛÙËÌ· ÌÂٷ͇ ÙˆÓ ¯‹˜ ‹ ηı›ÛÙ·Ù·È Î·Ù¿ ÙË ‰È·‰ÚÔÌ‹ Ù˘ ÓfiÛÔ˘ ·ÓıÂ- ÎÚ›ÛÂˆÓ (81%) Î·È Á) ªÂ ÙË ÌÔÚÊ‹ ·Ú·ÙÂٷ̤Ó˘ ÎÙÈÎfi ÛÙË ıÂڷ›· Ì ÙËÓ ¤ÓÓÔÈ· Ù˘ ÌË ·ÓÙ·fiÎÚÈ- Â̇ÚÂÙ˘ Ì˘·ÏÁ›·˜ (protracted febrile myalgia) ÛÙ· Û˘ ÛÙËÓ ÔÍ›· Î·È Ù˘ ÌË ·Ó·¯·›ÙÈÛ˘ ÙˆÓ ÎÚ›ÛˆÓ. Ï·›ÛÈ· Èı·Ó‹˜ ·ÁÁÂÈ›Ùȉ·˜ (11%), Ô˘ ··ÓÙ¿ ÛÙ· ¶ÚfiÛÊ·Ù· ¤¯ÂÈ ‰ÔÎÈÌ·ÛÙ› Û ·Ó¿ÏÔÁÔ˘˜ ·ÛıÂÓ›˜ ÛÙÂÚÔÂȉ‹. ÛÙËÓ ∂ÏÏ¿‰· Ë ¯ÔÚ‹ÁËÛË ÙÔ˘ anakinra ¿Óˆ ÛÙȘ ø˜ ‰ÂÚÌ·ÙÈ΋ Û˘ÌÌÂÙÔ¯‹ ÂÓ‰¤¯ÂÙ·È Ó· ÂÌÊ·Ó›- ÎÚ›ÛÂȘ, ¯ˆÚ›˜ ‰È·ÎÔ‹ Ù˘ ÎÔϯÈΛÓ˘, Ì ÂÓı·ÚÚ˘- ˙ÂÙ·È ÂÚ˘ÛÈÂÏ·ÙÔÂȉ¤˜ ÂÍ¿ÓıËÌ· ̤¯ÚÈ Î·È ÛÙÔ 40% ÓÙÈο ·ÔÙÂϤÛÌ·Ù·5. ∂Ó·ÏÏ·ÎÙÈΤ˜ ÚÔÙ¿ÛÂȘ ÛÂ ÙˆÓ ·ÛıÂÓÒÓ, ÂÓ‰¤¯ÂÙ·È ‰Â Ó· Â›Ó·È Î·È Ë ÌÔÓ·‰È΋ ·ÛıÂÓ›˜ ·ÓıÂÎÙÈÎÔ‡˜ ÛÙËÓ ÎÔϯÈΛÓË ·ÔÙÂÏÔ‡Ó ·Îfi- ÂΉ‹ÏˆÛË Ù˘ ÓfiÛÔ˘ Û ·È‰È¿. ÌË Ë ÈÓÙÂÚÊÂÚfiÓË-·, ·ÓÙÈ-TNF Î·È Ë ı·ÏȉÔÌ›‰Ë. μ‚·›ˆ˜, Ë ÛÔ‚·ÚfiÙÂÚË Î·È ÈÔ ·ÂÈÏËÙÈ΋ ÁÈ· ÙË ŸÛÔÓ ·ÊÔÚ¿ ÙËÓ ∂ÏÏ¿‰·, Ô ÔÈÎÔÁÂÓ‹˜ ÌÂÛÔÁÂÈ- ˙ˆ‹ ÂΉ‹ÏˆÛË ÙÔ˘ FMF ·ÔÙÂÏ› Ë Ù‡Ô˘ ∞∞ ·Ì˘- ·Îfi˜ ˘ÚÂÙfi˜, ·ÎÚˆÓ˘Ìȷο ÊÂÚfiÌÂÓÔ˜ Î·È ÛÙË ¯ÒÚ· ÏÔ›‰ˆÛË, Ë ÔÔ›· ÂÈÛ‡‰ÂÙ·È ·Ô˘Û›· ıÂڷ›·˜ Ì·˜ ˆ˜ FMF, ·ÔÙÂÏ› ÙÔ ÈÔ Û˘¯Ófi Î·È Î·Ï¿ ÌÂÏÂÙË- Î·È Ô‰ËÁ› Û‡ÓÙÔÌ· Û ÌË ·Ó·ÛÙÚ¤„ÈÌË ÓÂÊÚÈ΋ ·ÓÂ- ̤ÓÔ ÎÏËÚÔÓÔÌÔ‡ÌÂÓÔ ˘ÔÙÚÔÈ¿˙ÔÓ Â̇ÚÂÙÔ Û‡Ó- ¿ÚÎÂÈ·, ·ÏÏ¿ Î·È ‰˘Û·ÔÚÚfiÊËÛË. ∏ ÚԤϢÛË ‰ÚÔÌÔ. Δ· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·, ÙÚÂȘ ÌÂÁ¿Ï˜ ÌÂϤÙ˜, ÙˆÓ ÈÓȉ›ˆÓ ÙÔ˘ ∞∞ ·Ì˘ÏÔÂȉԇ˜ Â›Ó·È ¯·Ú·ÎÙËÚÈÛÙÈ- Ô˘ Û˘Ó‰‡·Û·Ó ÛÙÔȯ›· ·fi ÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË Î·È ÙË Î¿ Ë ˘ÂÚ·Ú·ÁfiÌÂÓË Î·Ù¿ ÙË ÊÏÂÁÌÔÓ‹ ÚˆÙ½ÓË ÁÂÓÂÙÈ΋ ·Ó¿Ï˘ÛË ÙÔ˘ ÊÂÚfiÌÂÓÔ˘ ˆ˜ ˘Â‡ı˘ÓÔ˘ ÁÔÓÈ- ÔÍ›·˜ Ê¿Û˘ SAA. ‰›Ô˘ MEFV, ¤ıÂÛ·Ó ÙȘ ‚¿ÛÂȘ ÁÈ· ÙËÓ Î·Ï‡ÙÂÚË Î·Ù·- ¢Â›ÎÙ˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ Ù˘ ÎÏÈÓÈ΋˜ ÔÚ›·˜ ÓfiËÛË Ù˘ ÎÏÈÓÈ΋˜ ·˘Ù‹˜ ÔÓÙfiÙËÙ·˜6-8. ø˜ Û˘ÌÂÚ¿- Ù˘ ÓfiÛÔ˘, ÂÎÙfi˜ ÙÔ˘ ∞∞ ·Ì˘ÏÔÂȉԇ˜ ÙÔ˘ ÔÚÔ‡, ÛÌ·Ù· ÌÔÚ› Ó· ·Ó·Ê¤ÚÂÈ Î·Ó›˜ fiÙÈ Ô FMF: ·ÔÙÂÏ› Ë C-·ÓÙȉÚÒÛ· ÚˆÙ½ÓË (CRP), Ù· ›‰· – ‰ÂÓ Â›Ó·È Û¿ÓÈ· ÓfiÛÔ˜ ÛÙËÓ ·ÙÚ›‰· Ì·˜, ΢- Ù˘ ÔÔ›·˜ Û˘Û¯ÂÙ›˙ÔÓÙ·È Ôχ ηϿ Ì ÙȘ ÂÍ¿ÚÛÂȘ Ú›ˆ˜ ÏfiÁˆ ÙÔ˘ ÌÂÙ·Ó·ÛÙ¢ÙÈÎÔ‡ Ú‡̷ÙÔ˜, Î·È ÂȉÈ- Î·È ÙȘ ˘Ê¤ÛÂȘ Ù˘ ÓfiÛÔ˘. ΔÔ ÂÚÁ·ÛÙËÚÈ·Îfi ÚÔÊ›Ï ÎfiÙÂÚ· ÙˆÓ ·ÙfiÌˆÓ Ì ηٷÁˆÁ‹ ·fi ÙËÓ ∞ÚÌÂÓ›·, Û˘ÌÏËÚÒÓÂÙ·È ·fi Ï¢ÎÔ΢ÙÙ¿ÚˆÛË Ì ÔÏ˘ÌÔÚ- – ηı˘ÛÙÂÚ› Ó· ‰È·ÁÓˆÛÙ› ÂÚ›Ô˘ 11 ¤ÙË, ΢- ÊÔ˘Ú‹ÓˆÛË, ¿ÓÔ‰Ô Ù˘ Ù·¯‡ÙËÙ·˜ ηı›˙ËÛ˘ ÙˆÓ Ú›ˆ˜ ÏfiÁˆ Ù˘ ¤ÏÏÂȄ˘ ÎÏÈÓÈ΋˜ ÂÁÚ‹ÁÔÚÛ˘ Î·È ‰˘- ÂÚ˘ıÚÒÓ (Δ∫∂) Î·È ·˘ÍË̤ӷ ›‰· ÊÂÚÚÈÙ›Ó˘ Î·È Ó·ÙfiÙËÙ·˜ ÁÂÓÂÙÈÎÔ‡ ÂϤÁ¯Ô˘, °. ªËÙÚÔ‡Ï˘, μ. ¶··‰fiÔ˘ÏÔ˜ 53
– Û˘Û¯ÂÙ›˙ÂÙ·È È‰È·›ÙÂÚ· ÛÙÂÓ¿ Ì ÙȘ ÌÂÙ·ÏÏ¿- te kinase deficiency associated periodic syndrome). ÍÂȘ ÛÙÔ ÁÔÓ›‰ÈÔ MEFV, ÙÔ ÔÔ›Ô Îˆ‰ÈÎÔÔÈ› ÁÈ· ÙËÓ ∏ ÎÚ›ÛË ÙÔ˘ HIDS x·Ú·ÎÙËÚ›˙ÂÙ·È Î˘Ú›ˆ˜ ·fi ˘Ú›ÓË, ·ÊÔ‡ ÛÙËÓ ∂ÏÏ¿‰· ·ÓȯÓ‡ÂÙ·È ÙÔ ÌÈÎÚfiÙÂÚÔ Â̇ÚÂÙÔ (100%), ÏÂÌÊ·‰ÂÓÔ¿ıÂÈ· (94%), ‰ÂÚÌ·ÙÈ- ÔÛÔÛÙfi ˘ÁÈÒÓ ÊÔÚ¤ˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ ÛÙÔ MEFV Τ˜ ÂΉËÏÒÛÂȘ (82%), ‰È¿ÚÚÔÈ· (82%), ·ÚıÚ·ÏÁ›Â˜ (<1,5%). (80%), ÊÚ›ÎÈ· (76%), ÎÔÈÏÈ·Îfi ¿ÏÁÔ˜ (72%), ·ÚıÚ›Ùȉ· (64%), Â̤ÙÔ˘˜ (56%) Î·È ÛÏËÓÔÌÂÁ·Ï›· (48%). ™Ë- ¶ÂÚÈÔ‰ÈÎfi Û‡Ó‰ÚÔÌÔ Ô˘ Û¯ÂÙ›˙ÂÙ·È ÌÂÈÒÓÔÓÙ·È ·ÎfiÌË ÔÈ ÛÙÔÌ·ÙÈΤ˜ ¿Êı˜ Î·È Ë Ó¤ÎÚˆ- Ì ÙÔÓ ˘Ô‰Ô¯¤· ÙÔ˘ TNF (TRAPS – ÛË ÙÔ˘ ‰¤ÚÌ·ÙÔ˜ ÌÂÙ¿ ·fi ‰ÈÂÓ¤ÚÁÂÈ· ‰ÔÎÈÌ·Û›·˜ TNF-receptor associated periodic Mantoux. ø˜ ÂÎÏ˘ÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ ıˆÚÔ‡ÓÙ·È Ë Â›- 1,10,12 syndrome) ÎÙËÙË ·ÓÔÛÔÔ›ËÛË Î·È ÔÈ ÈÔÁÂÓ›˜ ÏÔÈÌÒÍÂȘ . √È ÎÚ›ÛÂȘ ‰È·ÚÎÔ‡Ó ÂÚ›Ô˘ Ì›· ‚‰ÔÌ¿‰·. ∏ ΔÔ TRAPS Â›Ó·È ÙÔ ·Ì¤Ûˆ˜ Û˘¯ÓfiÙÂÚÔ ÎÏËÚÔÓÔÌÔ‡- Û˘¯ÓfiÙËÙ¿ ÙÔ˘˜ ÌÔÚ› Ó· Â›Ó·È ·ÚÎÂÙ¿ ÌÂÁ¿ÏË, ·Îfi- ÌÂÓÔ ˘ÔÙÚÔÈ¿˙ÔÓ Â̇ÚÂÙÔ Û‡Ó‰ÚÔÌÔ ÌÂÙ¿ ÙÔÓ ÌË Î·È ¿Óˆ ·fi Ì›· ÊÔÚ¿ ÙÔÓ Ì‹Ó·. §Â˘ÎÔ΢ÙÙ¿- FMF. ÷ڷÎÙËÚ›˙ÂÙ·È Î˘Ú›ˆ˜ ·fi Â̇ÚÂÙÔ (100%), ÚˆÛË Î·È ÎÈÓËÙÔÔ›ËÛË ÚˆÙÂ˚ÓÒÓ ÔÍ›·˜ Ê¿Û˘ Û˘- ÎÔÈÏÈ·Îfi ¿ÏÁÔ˜ (88%), ‰ÂÚÌ·ÙÈΤ˜ ÂΉËÏÒÛÂȘ (88%), ÓÔ‰Â‡Ô˘Ó ÙȘ ÎÚ›ÛÂȘ. ΔÔ Î˘ÚÈfiÙÂÚÔ ¯·Ú·ÎÙËÚÈÛÙÈÎfi Ì˘·ÏÁ›Â˜ (80%), ÎÂÊ·Ï·ÏÁ›· (68%), ·ÚıÚ·ÏÁ›Â˜ (52%), fï˜ Ù˘ ÓfiÛÔ˘ Â›Ó·È Ù· ˘„ËÏ¿ ›‰· ÔÏ˘ÎψÓÈ- ÂÓıÂÛÔ¿ıÂÈ· (44%) Î·È Ï¢ÚÈÙÈÎfi ¿ÏÁÔ˜ (40%)9,10. ΋˜ IgD, Ô˘ ·Ó¢ڛÛÎÔÓÙ·È ÛÙÔ˘˜ ÂÚÈÛÛfiÙÂÚÔ˘˜ √È ÎÚ›ÛÂȘ ‰È·ÚÎÔ‡Ó ÔˆÛ‰‹ÔÙ ¿Óˆ ·fi Ì›· ·ÛıÂÓ›˜, ¯ˆÚ›˜ ˆÛÙfiÛÔ Ó· ·ÔÙÂÏÔ‡Ó ‰Â›ÎÙË ÂÓÂÚ- ‚‰ÔÌ¿‰·Ø Û ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ Ù· Û˘ÌÙÒÌ·- ÁfiÙËÙ·˜ Ù˘ ÓfiÛÔ˘1,10. Ù· ÌÔÚÔ‡Ó Ó· ·Ú·Ù·ıÔ‡Ó Ì¤¯ÚÈ Î·È ÙÚÂȘ ‹ Î·È Â- ™ÙË ıÂڷ›· ¤¯Ô˘Ó ‰ÔÎÈÌ·ÛÙ› ÂÎÙfi˜ ·fi Ù· ÚÈÛÛfiÙÂÚ˜ ‚‰ÔÌ¿‰Â˜, ÂÌÊ·Ó›˙ÔÓÙ·˜ ¤ÙÛÈ ÙËÓ ÂÈÎfi- ÛÙÂÚÔÂȉ‹ Î·È Ë ÛÈÌ‚·ÛÙ·Ù›ÓË (˘ÂÓı˘Ì›˙ÂÙ·È fiÙÈ Ô Ó· ÂÌ˘Ú¤ÙÔ˘ ·ÁÓÒÛÙÔ˘ ·ÈÙÈÔÏÔÁ›·˜ Û ·‰È¿ÁÓˆÛÙ· Û¯ËÌ·ÙÈÛÌfi˜ ÙÔ˘ Ì‚·ÏÔÓÈÎÔ‡ Â›Ó·È ¤Ó· ‚‹Ì·-ÎÏÂȉ› ÂÚÈÛÙ·ÙÈο. ∏ ·ӿÏË„Ë ÙˆÓ ÎÚ›ÛÂˆÓ ‰ÂÓ ÌÔÚ› ÛÙË ‚ÈÔÛ‡ÓıÂÛË Ù˘ ¯ÔÏËÛÙÂÚfiÏ˘). ¶ÚfiÛÊ·Ù˜ ‰Ô- Ó· ÚÔ‚ÏÂÊı› ¯ÚÔÓÈο, Û˘Ó‹ıˆ˜ fï˜ ·˘Ùfi Û˘Ì- ÎÈ̤˜ Ì etanercept Î·È anakinra ¤¯Ô˘Ó ‰ÒÛÂÈ Â˘ÓÔ˚- ‚·›ÓÂÈ Î¿ı 6 ¤ˆ˜ 12 Ì‹Ó˜. ο ·ÔÙÂϤÛÌ·Ù·13,14. ø˜ ÂÚÁ·ÛÙËÚȷο Â˘Ú‹Ì·Ù· ·Ó·Ì¤ÓÔÓÙ·È ÂÎÛÂ- ÛËÌ·Ṳ̂ÓË Ï¢ÎÔ΢ÙÙ¿ÚˆÛË Î·È ·‡ÍËÛË ÚˆÙÂ˚ÓÒÓ ∫Ú˘Ô·ÁÒÌÂÓÔ ·˘ÙÔÊÏÂÁÌÔÓ҉˜ ÔÍ›·˜ Ê¿Û˘. ø˜ ‰Â›ÎÙ˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ Ù˘ Û‡Ó‰ÚÔÌÔ (CAPS – Cold induced au- 1 ÂÓÂÚÁfiÙËÙ·˜ Ù˘ ÓfiÛÔ˘ Ï·Ì‚¿ÓÂÙ·È Û˘Ó‹ıˆ˜ Ë CRP . toinflammatory syndrome 1 [CIAS1] ∏ ıÂڷ›· ÙÔ˘ TRAPS ÂÚÈÏ·Ì‚¿ÓÂÈ ÛÙÂÚÔÂȉ‹ associated periodic syndrome) Î·È Î·Ù¿ ÂÚ›ÙˆÛË ·ÓÙÈ-TNF ‚ÈÔÏÔÁÈο ·Ó¿ÏÔÁ·. ¶·ÚfiÏÔ Ô˘ ıˆÚËÙÈο Ë ·Ó·ÛÙÔÏ‹ Ù˘ ‰Ú¿Û˘ ÙÔ˘ ¶ÚfiÎÂÈÙ·È ÁÈ· ¤Ó· Û‡Ó‰ÚÔÌÔ Ì ÙÚÂȘ ‰È·ÎÚÈÙ¤˜ Û˘ÓÈ- TNF ı· ÌÔÚÔ‡Û ӷ ÂÍ·ÛÊ·Ï›ÛÂÈ ¤Ó· ÏÂÔÓ¤ÎÙËÌ· ÛÙÒÛ˜: ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì TRAPS, Û ÔÏϤ˜ ÂÚÈÙÒÛÂȘ Ë ·) ™‡Ó‰ÚÔÌÔ Muckle-Wells (MWS), Ô˘ ÂÚÈ- ¯ÔÚ‹ÁËÛË ÙÔ˘ etanercept ‰ÂÓ Û˘Óԉ‡ÙËΠ·fi ·Ó¿- Ï·Ì‚¿ÓÂÈ ÎÒʈÛË, ‰˘ÛÌÔÚÊ›· ÎÚ·Ó›Ô˘, ·ۂÂÛÙÒ- ÏÔÁÔ fiÊÂÏÔ˜, ÂÓÒ ÂÈϤÔÓ ˘¿Ú¯Ô˘Ó ·Ó¤Î‰ÔÙ˜ ÛÂȘ ÌËÓ›ÁÁˆÓ, Ô›‰ËÌ· ıËÏ‹˜ Î·È ÂΉËÏÒÛÂȘ ·fi ÙȘ ·Ó·ÊÔÚ¤˜ fiÙÈ ÙÔ infliximab Ô‰‹ÁËÛ ·ÎfiÌË Î·È Û ·ÚıÚÒÛÂȘ Î·È ÙÔ ‰¤ÚÌ·, Âȉ›ӈÛË ÔÚÈṲ̂ӷ ÂÚÈÛÙ·ÙÈο9,11. ‚) √ÈÎÔÁÂÓ‹˜ ÎÚ˘Ô·ÁÒÌÂÓË Ô˘ÚÙÈοÚÈ· (FCU – Familial cold urticaria)/√ÈÎÔÁÂÓ¤˜ ÎÚ˘Ô·ÁÒÌÂÓÔ ¶ÂÚÈÔ‰ÈÎfi Û‡Ó‰ÚÔÌÔ Ô˘ Û˘Óԉ‡Â- ·˘ÙÔÊÏÂÁÌÔÓ҉˜ Û‡Ó‰ÚÔÌÔ (FCAS – Familial cold Ù·È ·fi ·Ó¿ÚÎÂÈ· Ù˘ Ì‚·ÏÔÓÈ΋˜ autoinflammatory syndrome), Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÎÈÓ¿Û˘ (MAPS – Mevalonate kinase ¤ÎÏ˘ÛË ÂÍ·Óı‹Ì·ÙÔ˜, ·ÚıÚ·ÏÁÈÒÓ Î·È ·ÚıÚ›Ùȉ·˜ ÌÂÙ¿ ·fi deficiency associated periodic syn- ¤ÎıÂÛË Û ÎÚ‡Ô Î·È drome) Á) ÃÚfiÓÈÔ Ó¢ÚÔ-‰ÂÚÌ·ÙÔ-·ÚıÚÈÎfi Û‡Ó‰ÚÔÌÔ ‚ÚÂÊÒÓ (CINCA – Chronic infantile neurological cu- ΔÔ ÂÚÈÔ‰ÈÎfi Û‡Ó‰ÚÔÌÔ Ô˘ Û˘Óԉ‡ÂÙ·È ·fi ˘ÂÚ- taneous articular syndrome)/™‡Ó‰ÚÔÌÔ ÔÏ˘Û˘ÛÙË- Á·ÌÌ·ÛÊ·ÈÚÈÓ·ÈÌ›· D (HIDS – Hyperimmunoglobuli- Ì·ÙÈ΋˜ ÊÏÂÁÌÔÓÒ‰Ô˘˜ ·¿ÓÙËÛ˘ ÓÂÔÁÓÒÓ (NO- naemia D with periodic fever syndrome), Ì·˙› Ì ÙË ÌÂ- MID – Neonatal onset multisystem inflammatory di- ‚·ÏÔÓÈ΋ Ô͢Ԣڛ· (MA – mevalonic aciduria), ··ÚÙ›- sease), Ô˘ ÂΉËÏÒÓÂÙ·È Î·Ù¿ ÙË ÓÂÔÁÓÈ΋ ËÏÈΛ· Î·È ˙Ô˘Ó ÙÔ ÂÚÈÔ‰ÈÎfi Û‡Ó‰ÚÔÌÔ Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ·ÓÂ- ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ·ÓÂͤÏÂÁÎÙË ÊÏÂÁÌÔÓÒ‰Ë ·ÓÙ›- ¿ÚÎÂÈ· Ù˘ Ì‚·ÏÔÓÈ΋˜ ÎÈÓ¿Û˘ (MAPS – Mevalona- ‰Ú·ÛË Û ÔÏÏ·Ï¿ fiÚÁ·Ó· Î·È ÈÛÙÔ‡˜, Ì ·ÚÈ· 54 ™˘ÛÙËÌ·ÙÈο ·˘ÙÔÊÏÂÁÌÔÓÒ‰Ë ÓÔÛ‹Ì·Ù·
ÂÓÙfiÈÛË ÙÔ ‰¤ÚÌ·, ÙȘ ·ÚıÚÒÛÂȘ Î·È ÙȘ Ì‹ÓÈÁÁ˜, ÚfiÏÔ˜ Ù˘ ÔÌÔ˙˘ÁˆÙ›·˜ R202Q, Ô˘ ÂıˆÚ›ÙÔ Ì¤- ·fi fiÔ˘ Î·È ÚÔ·ÙÔ˘Ó ÔÈ ¯·Ú·ÎÙËÚÈÛÙÈΤ˜ ÁÈ· ÙÔ ¯ÚÈ ÚfiÙÈÓÔ˜ ÌË Û˘ÓÒÓ˘ÌÔ˜ ÔÏ˘ÌÔÚÊÈÛÌfi˜, ˆ˜ Û‡Ó‰ÚÔÌÔ Ó¢ÚÔÏÔÁÈΤ˜ ‚Ï¿‚˜1,10. Û¯ÂÙÈ˙fiÌÂÓ˘ Ì FMF, Ë ·ÚÔ˘Û›· ÌÂÙ·ÏÏ¿ÍÂˆÓ ‹ ¿Ï- ™ÙË ıÂڷ›· ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ÛÙÂÚÔÂȉ‹ Î·È a- ÏˆÓ ÂÈÁÂÓÂÙÈÎÒÓ ÙÚÔÔÔÈ‹ÛˆÓ, ÎÔÓÙ¿ ‹ Ì·ÎÚÈ¿ nakinra, Ì ı·̷ÙÈο ·ÔÙÂϤÛÌ·Ù· fiÛÔÓ ·ÊÔÚ¿ ÙË ·fi ÙÔ MEFV, Ô˘ Ó· Ô‰ËÁÔ‡Ó Â›Û˘ Û ʷÈÓfiÙ˘Ô ¯Ú‹ÛË ÙÔ˘ ÙÂÏÂ˘Ù·›Ô˘ Û ·ÂÈÏËÙÈΤ˜ ÁÈ· ÙË ˙ˆ‹ Â- FMF, ‰ÂÓ ÌÔÚ› Ó· ·ÔÎÏÂÈÛÙ›8. ÚÈÙÒÛÂȘ CINCA/NOMID15. ¶ÚfiÛÊ·Ù· ‰ÔÎÈÌ¿˙Â- ŒÓ· ·ÚfiÌÔÈÔ Ê·ÈÓfiÌÂÓÔ ‰ÈÂÚ¢ӋıËΠ·fi ÂÏ- Ù·È (Û ʿÛË πππ) ÙÔ canakinumab, ¤Ó· Ï‹Úˆ˜ ·Ó- ÏËÓÈ΋ ÔÌ¿‰· Û ·ÛıÂÓ›˜ Ì ÂÏÎÒ‰Ë ÎÔÏ›Ùȉ·, fiÔ˘ ıÚÒÈÓÔ ÌÔÓÔÎψÓÈÎfi ·Óٛۈ̷ ÂÓ·ÓÙ›ÔÓ Ù˘ ÈÓÙÂÚ- ‚Ú¤ıËΠfiÙÈ ÔÈ ¿Û¯ÔÓÙ˜ ·fi ÙË ÓfiÛÔ, ÔÈ ÔÔ›ÔÈ Ù·˘- Ï¢ΛÓ˘-1‚16. ÙÔ¯ÚfiÓˆ˜ ÂÌÊ¿ÓÈ˙·Ó Â͈ÂÓÙÂÚÈΤ˜ ÂΉËÏÒÛÂȘ (΢- Ú›ˆ˜ ·ÚıÚ›Ùȉ·), ›¯·Ó Û ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈÎfi ‚·ıÌfi √ ÚfiÏÔ˜ ÙÔ˘ «Ê˘ÛÈÎÔ‡ ÂÈÚ¿Ì·ÙÔ˜» ·˘ÍË̤ӷ ÔÛÔÛÙ¿ ÌÂÙ·ÏÏ¿ÍÂˆÓ ÛÙÔ MEFV24. ∫·È ÛÙËÓ ÛÙË ‰È·Ï‡ηÓÛË ÌÔÚÈ·ÎÒÓ Ì˯·ÓÈ- ÂÚ›ÙˆÛË ·˘Ù‹ ‰ÂÓ ÌÔÚ› Ó· ˘ÔÛÙËÚȯı› Ì ‚‚·È- ÛÌÒÓ: ÙÔ ·Ú¿‰ÂÈÁÌ· ÙˆÓ ·˘ÙÔÊÏÂÁ- fiÙËÙ· fiÙÈ ÔÈ ÌÂÙ·ÏÏ¿ÍÂȘ Ù˘ ˘Ú›Ó˘ ÂÈ‚·Ú‡ÓÔ˘Ó ÙÔÓ ÌÔÓˆ‰ÒÓ ÓÔÛËÌ¿ÙˆÓ Ê·ÈÓfiÙ˘Ô Ù˘ ÂÏÎÒ‰Ô˘˜ ÎÔÏ›Ùȉ·˜, ÌÔÏÔÓfiÙÈ Ì›· Ù¤- ÙÔÈ· ˘fiıÂÛË Â›Ó·È ·fiÏ˘Ù· ‰ÈηÈÔÏÔÁË̤ÓË. ∞Ó¿ÏÔÁ˜ ·) ªÂÙ·ÏÏ¿ÍÂȘ ÙÔ˘ MEFV ÌÂϤÙ˜ Ì ıÂÙÈο Â˘Ú‹Ì·Ù· ¤¯Ô˘Ó Á›ÓÂÈ Î·È ÁÈ· ÙË Ófi- ÛÔ Crohn, ÚÈÓ ·ÎfiÌË ‚ÚÂı› fiÙÈ ¤Ó· ̤ÚÔ˜ ÙˆÓ ·ÛıÂ- ∏ ηٿ‰ÂÈÍË Ù˘ ÌÔÚȷ΋˜ ‚Ï¿‚˘ ÔÚÈṲ̂ӈÓ, ÙÔ˘- ÓÒÓ ·˘ÙÒÓ ·ÚÔ˘ÛÈ¿˙ÂÈ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ NOD2, ¤Ó·· Ï¿¯ÈÛÙÔÓ, ·fi Ù· ·˘ÙÔÊÏÂÁÌÔÓÒ‰Ë ÓÔÛ‹Ì·Ù·, ¤¯ÂÈ ÁÔÓ›‰ÈÔ Ô˘ Έ‰ÈÎÔÔÈ› ÁÈ· ¤Ó·Ó ÂÓ‰Ô΢ÙÙ¿ÚÈÔ ˘Ô- ‰ÒÛÂÈ Ì›· Ó¤· ÒıËÛË ÛÙË ‰È·Ï‡ηÓÛË ÙˆÓ ÌÔÚÈ·ÎÒÓ ‰Ô¯¤· ÛËÌ¿ÙˆÓ ÎÈÓ‰‡ÓÔ˘ Û¯ÂÙÈ˙fiÌÂÓÔ Ì ÌÈÎÚÔÔÚÁ·- ÌÔÓÔ·ÙÈÒÓ Ù˘ ÊÏÂÁÌÔÓ‹˜ Î·È Ù˘ Û‡Ó‰ÂÛ‹˜ ÙÔ˘˜ ÓÈÛÌÔ‡˜, Î·È ¿Ú· Û˘Ó‰¤ÂÙ·È ¿ÌÂÛ· Ì ‰È·Ù·Ú·¯¤˜ Ù˘ Ì ÙÔ ÂÓ‰ÔÁÂÓ¤˜ Û‡ÛÙËÌ· ·ÓÔÛ›·˜1,17-19. ÂÓ‰ÔÁÂÓÔ‡˜ ·ÓÔÛ›·˜. ΔÔ NOD2 ÂÌÊ·Ó›˙ÂÈ Â›Û˘ ÌÂ- ø˜ ÚÒÙÔ˜ ÎÚ›ÎÔ˜ ÛÙËÓ ·Ï˘Û›‰· ÙˆÓ ÁÂÁÔÓfiÙˆÓ Ù·ÏÏ¿ÍÂȘ (Û ¿ÏϘ ÂÚÈÔ¯¤˜ ÙÔ˘ ÁÔÓȉ›Ô˘) ÛÙÔ Û‡Ó- Ô˘ ¤ÌÂÏÏ ӷ ÂÍÂÏȯıÔ‡Ó, ‹ÚıÂ Ë Ù·˘ÙÔÔ›ËÛË ÙÔ˘ ‰ÚÔÌÔ Blau, Ì›· ÔÓÙfiÙËÙ· Ô˘ ÂÚÈÏ·Ì‚¿ÓÂÈ, fiˆ˜ Î·È MEFV, ÙÔ˘ ÁÔÓȉ›Ô˘ Ô˘ Έ‰ÈÎÔÔÈ› ÁÈ· ÙËÓ ÚˆÙ½- Ë ÓfiÛÔ˜ Crohn, ÎÔÎÎȈ̷ÙÒ‰Ë ÊÏÂÁÌÔÓ‹. ÓË ˘Ú›ÓË, ˆ˜ ÙÔ˘ ΢ڛԢ ˘fiÙÔ˘ ÁÈ· ÙÔÓ FMF: ªÂ- ∂ȉÈο ÛÙËÓ ÂÚ›ÙˆÛË ÙÔ˘ FMF, Ë ¤ÏÏÂÈ„Ë ÁÂÓÂ- Ù·‚ÔϤ˜ Û ÔÚÈṲ̂Ó˜ ı¤ÛÂȘ Ù˘ Έ‰ÈÎÔÔÈÔ‡Û·˜ ÙÈ΋˜ ÈÛÔÚÚÔ›·˜ ‚¿ÛÂÈ Ù˘ ·Ú¯‹˜ Hardy-Weinberg, ÂÚÈÔ¯‹˜ (΢ڛˆ˜ ÂÍfiÓÈ· 2 Î·È 10) Ô‰ËÁÔ‡Û·Ó Ì ¿Ï- ÂΉËÏÔ‡ÌÂÓË ˆ˜ ÌË ÂÍ·Ê¿ÓÈÛË ÙˆÓ ÌÂÙ·ÏÏ·ÁÌ¤ÓˆÓ ÏÔÙ ¿ÏÏË ‰ÈÂÈÛ‰˘ÙÈÎfiÙËÙ· Û ¿ÏÏÔÙ ¿ÏÏ˘ ‚·Ú‡ÙË- ·ÏÏËÏÔÌfiÚÊˆÓ ÙÔ˘ MEFV, ÌÔÚ› Ú·ÎÙÈο Ó· ÂÍËÁË- Ù·˜ Ê·ÈÓfiÙ˘Ô20,21. ΔÔ ÁÂÁÔÓfi˜ ·˘Ùfi ¤Ù˘¯Â ȉȷ›ÙÂÚ˘ ı› ÌfiÓÔ Ì¤Ûˆ Ù˘ Û˘ÓÙ‹ÚËÛ˘ ÏÂÔÓÂÎÙ‹Ì·ÙÔ˜ ¤Ú¢ӷ˜: ∞ԉ›¯ıËΠfiÙÈ ÔÈ ÌÂÙ·ÏÏ¿ÍÂȘ, Ô˘ Ô- ÛÙÔ˘˜ ÂÙÂÚÔ˙˘ÁÒÙ˜23. ¶ÔÈÔ ı· ÌÔÚÔ‡Û fï˜ Ó· ‰ËÁÔ‡Û·Ó Û ÈÔ ÛÔ‚·Ú‹ ÎÏÈÓÈ΋ ÂÈÎfiÓ·, ‰ڿ˙ÔÓÙ·Ó Â›Ó·È ·˘Ùfi ÙÔ ÏÂÔÓ¤ÎÙËÌ·; Œ¯ÂÈ ˘ÔÛÙËÚȯı›, fi¯È ¿- ΢ڛˆ˜ ÛÙÔ ÂÍfiÓÈÔ 10, Ô˘ ·ÊÔÚÔ‡Û·Ó Ì›· ÂÚÈÔ¯‹ ÓÙ· ¯ˆÚ›˜ ÂÈÛÙÈΤ˜ ÂӉ›ÍÂȘ, fiÙÈ Ô FMF ÚÔÛٷهÂÈ ÙÔ˘ ηڂÔ͢ÙÂÏÈÎÔ‡ ¿ÎÚÔ˘ Ù˘ ˘Ú›Ó˘, Ô˘ ηÏÂ›Ù·È ·fi ÔÚÈṲ̂Ó˜ ÏÔÈÌÒÍÂȘ, ›Ù ÂÓ‰Ô΢ÙÙ¿ÚȘ ÌÈÎÚÔ- B30.2 (SPRY) Î·È ·ÔÙÂÏ› ÂÚÈÔ¯‹ Û‡Ó‰ÂÛ˘ ‹ ÌÂ- ‚ȷΤ˜ (.¯., Ê˘Ì·Ù›ˆÛË, ‚ÚԢΤÏψÛË), ›Ù ÈÔÁÂÓ›˜ Ù¿‰ÔÛ˘ Û‹Ì·ÙÔ˜. ø˜ ·ÔÙ¤ÏÂÛÌ·, ÔÈ ÌÂÙ·ÏÏ¿ÍÂȘ (¢ÏÔÁÈ¿). ∂›Û˘, Û˘˙ËÙÂ›Ù·È Ë Èı·ÓfiÙËÙ· Ë ÌÂÙ·Ï- Û ·˘Ù‹Ó ÙËÓ Î·ıÔÚÈÛÙÈ΋˜ ÛËÌ·Û›·˜ ÂÚÈÔ¯‹ Ô‰Ë- Ï·Á̤ÓË ˘Ú›ÓË Ó· ·ÔÙÂÏ› Ò˜ ¤Ó·Ó ‚·ıÌfi ¤Ó· ÊÚ¤- ÁÔ‡Ó Û ηı˘ÛÙÂÚË̤ÓË ·fiÙˆÛË Î·È ÊÏÂÁÌÔÓ‹ ̤- ÓÔ ÛÙËÓ ˘ÂÚ‚ÔÏÈ΋ Th2 ·ÓÙ›‰Ú·ÛË Ô˘ Û˘Óԉ‡ÂÈ ÙÔ Ûˆ Ù˘ ·‰˘Ó·Ì›·˜ Ù˘ ÌË ÏÂÈÙÔ˘ÚÁÈ΋˜ ˘Ú›Ó˘ Ó· ·- ¿ÛıÌ·, Î·È ¤ÙÛÈ Ë ‡·ÚÍË ÛËÌ·ÓÙÈ΋˜ ÂÚÈ‚·ÏÏÔÓÙÈ΋˜ Ó·ÛÙ›ÏÂÈ ÙËÓ ·Ú·ÁˆÁ‹ IL-1‚22. ›ÂÛ˘ (·˘ÍË̤ÓË ¤ÎıÂÛË Û ·ÏÏÂÚÁÈÔÁfiÓ·) Ó· ·ÔÙÂ- Δ· ÁÂÓÈο Û˘ÌÂÚ¿ÛÌ·Ù· ·fi ÙË Ì¤¯ÚÈ ÙÒÚ· Ï› ¤Ó·Ó ÎÈÓËÙ‹ÚÈÔ Ì˯·ÓÈÛÌfi Û˘ÓÙ‹ÚËÛ˘ Ù˘ Û˘¯Ófi- ·ÁÎfiÛÌÈ· ÂÌÂÈÚ›· ‰Â›¯ÓÔ˘Ó fiÙÈ ¤ÓÙ ÙÔ˘Ï¿¯ÈÛÙÔÓ ÙËÙ·˜ ÙˆÓ «·ıÔÏÔÁÈÎÒÓ» ·ÏÏËÏÔÌfiÚʈÓ25. ÌÂÙ·ÏÏ¿ÍÂȘ (M694V, V726A, M680I, E148Q Î·È M694I) ÂÍËÁÔ‡Ó ¿Óˆ ·fi ÙÔ 70% ÙÔ˘ Û˘Ì‚·ÙÔ‡ Ì FMF Ê·ÈÓÔÙ‡Ô˘23. ΔÈ Á›ÓÂÙ·È fï˜ Ì ÙÔ ˘fiÏÔÈÔ ‚) ªÂÙ·ÏÏ¿ÍÂȘ ÙÔ˘ CIAS1/NALP3 30%; ¶ÂÚ›Ô˘ ÔÈ ÌÈÛÔ› ·fi ·˘ÙÔ‡˜ ÙÔ˘˜ ·ÛıÂÓ›˜ ∂ÎÙfi˜ Ù˘ ˘Ú›Ó˘, ¤Ó· ¿ÏÏÔ ÌfiÚÈÔ, Ë ÎÚ˘Ô˘Ú›ÓË, ·ÚÔ˘ÛÈ¿˙Ô˘Ó ¿ÏϘ, Û·ÓÈfiÙÂÚ˜ Î·È ÂӉ¯Ô̤ӈ˜ ÚÔ˚fiÓ ÙÔ˘ ÁÔÓȉ›Ô˘ CIAS1/NALP3, Ô˘ ¢ڛÛÎÂÙ·È ‰ËψÙÈΤ˜ ηٷÁˆÁ‹˜ ÌÂÙ·ÏÏ¿ÍÂȘ ¿Óˆ ÛÙÔ MEFV. ÌÂÙ·ÏÏ·Á̤ÓÔ ÛÙÔ ÎÚ˘Ô·ÁÒÌÂÓÔ ·˘ÙÔÊÏÂÁÌÔÓÒ- √È ˘fiÏÔÈÔÈ ‰ÂÓ ¤¯Ô˘Ó η̛· ‚Ï¿‚Ë ÛÙÔ MEFV. ¶·- ‰Â˜ Û‡Ó‰ÚÔÌÔ, Ê·›ÓÂÙ·È Ó· ·ÔÙÂÏ› ¤Ó· ‚·ÛÈÎfi Û˘- ÚfiÏÔ Ô˘ ÛÙËÓ ÙÂÏÂ˘Ù·›· ÔÌ¿‰· ¤¯ÂÈ ˘ÔÛÙËÚȯı› Ô ÛÙ·ÙÈÎfi Ù˘ Ú‡ıÌÈÛ˘ Ù˘ ÊÏÂÁÌÔÓÒ‰Ô˘˜ ‰ÈÂÚÁ·- °. ªËÙÚÔ‡Ï˘, μ. ¶··‰fiÔ˘ÏÔ˜ 55
Û›·˜. √ ÚfiÏÔ˜ Ù˘ ÎÚ˘Ô˘Ú›Ó˘, ȉȷ›ÙÂÚ· Û ۯ¤ÛË ‰) ∞fi ÙË ÌÔÚȷ΋ ‚Ï¿‚Ë ÛÙÔÓ ıÂڷ¢ÙÈÎfi Ì ÙËÓ ˘Ú›ÓË, ‰ÂÓ ¤¯ÂÈ ‰È¢ÎÚÈÓÈÛÙ› Ï‹Úˆ˜, ·Ó Î·È ÛÙfi¯Ô Ê·›ÓÂÙ·È fiÙÈ Î·È Ù· ‰‡Ô ÌfiÚÈ· ¤¯Ô˘Ó ˆ˜ ÛÙfi¯Ô ÙËÓ ¶·ÚfiÏÔ Ô˘ Û ÔÏϤ˜ ÂÚÈÙÒÛÂȘ Ë ÌÔÚȷ΋ ·ıÔ- ηۿÛË-1, ̤ۈ ÔÏ˘ÌÂÚÈÛÌÔ‡ ÙÔ˘ ASC (apo- ÏÔÁ›· ‰ÂÓ ¤¯ÂÈ Ï‹Úˆ˜ ‰È·Ï¢ηÓı›, ÂÌÊ·Ó›˙ÂÙ·È Ó· ptosis-associated speck-like protein containing a ¿Û¯ÂÈ Â›ÙÂ Ë Ô‰fi˜ ÛÙËÓ ÔÔ›· ÂÌϤÎÂÙ·È Ë Ì¤Ûˆ Ô- CARD)26,27. ¶ÚfiÛÊ·Ù· Ë ÔÌ¿‰· ÙÔ˘ Kastner ·¤- Ï˘ÌÔÚÈ·ÎÒÓ Û˘ÌÏÂÁÌ¿ÙˆÓ, Û˘ÏÏ‹‚‰ËÓ Î·ÏÔ‡ÌÂÓˆÓ ‰ÂÈÍ fiÙÈ Ë ˘Ú›ÓË Ú˘ıÌ›˙ÂÈ ÙËÓ ÂÓÂÚÁÔÔ›ËÛË Ù˘ ˆ˜ ÊÏÂÁÌÔÓÔۈ̿وÓ, ÂÓÂÚÁÔÔ›ËÛË Ù˘ IL-1‚ Î·È ·- ηۿÛ˘-1 Î·È ÂÓ Û˘Ó¯›· Ù˘ ÈÓÙÂÚÏ¢ΛÓ˘-1‚. ÂÏ¢ı¤ÚˆÛË ÙÔ˘ TNF, ›Ù ٷ ÌfiÚÈ· Ô˘ ¤¯Ô˘Ó Û¯¤- ∂ÎÙfi˜ ÙÔ‡ÙÔ˘, Ë ›‰È· Ë ˘Ú›ÓË ·ÔÙÂÏ› ˘fiÛÙڈ̷ ÛË Ì ÙËÓ ·Ó›¯Ó¢ÛË ÛËÌ¿ÙˆÓ ÎÈÓ‰‡ÓÔ˘. ŸÛÔÓ ·ÊÔÚ¿ ÁÈ· ÙËÓ Î·Û¿ÛË-1, ̤ۈ Ù˘ ÔÔ›·˜ ·ÔÎfiÙÂÙ·È ÙË Û‡Ó‰ÂÛË Ù˘ ÌË ÂȉÈ΋˜ ·ÓÔÛ›·˜ Ì ÙË ÊÏÂÁÌÔÓÒ‰Ë ÙÔ ·ÌÈÓÔÙÂÏÈÎfi ¿ÎÚÔ, Ô˘ Ì ÙË ÛÂÈÚ¿ ÙÔ˘ ‰ÈÂÁ›ÚÂÈ ·¿ÓÙËÛË, ‰ÈÂÚÂ˘Ó¿Ù·È Ô ÚfiÏÔ˜ ÙˆÓ Toll-like ˘Ô‰Ô- 28 ÙÔ ÌÔÓÔ¿ÙÈ ÙÔ˘ ÌÂÙ·ÁÚ·ÊÈÎÔ‡ ·Ú¿ÁÔÓÙ· nF-Îμ . ¯¤ˆÓ (TLRs)31. ∫˘Ú›ˆ˜ Ì ·ÊÔÚÌ‹ ÙËÓ ÚÒÙË Î·ÙËÁÔ- ∞fi ÙËÓ ¿ÏÏË, Ë ÎÚ˘Ô˘Ú›ÓË, Û˘ÌÌÂÙ¤¯ÂÈ Ì·˙› Ì ڛ· ÌÔÚÈ·ÎÒÓ ·ıÔÁÂÓÂÙÈÎÒÓ Ì˯·ÓÈÛÌÒÓ, ¤¯Ô˘Ó ÚÔ- ÙÔÓ ASC Û ¤Ó· ÌÔÚÈ·Îfi Û‡ÌÏÂÁÌ· Ô˘ ηÏÂ›Ù·È Ù·ı› Î·È ‰ÔÎÈÌ·ÛÙ› ÂÈÙ˘¯Ò˜ ıÂڷ›˜ Ì ‚ÈÔÏÔÁÈ- ÊÏÂÁÌÔÓfiۈ̷ (inflammasome), Ô˘ ˆ˜ ÙÂÏÈ΋ ÙÔ˘ ÎÔ‡˜ ·Ú¿ÁÔÓÙ˜, fiˆ˜ ÔÈ ·ÓÙÈ-TNF ·Ú¿ÁÔÓÙ˜ eta- ·ÔÛÙÔÏ‹ ¤¯ÂÈ ÙËÓ ÂÓÂÚÁÔÔ›ËÛË Ù˘ ÚÔηۿ- nercept (Enbrel®), infliximab (Remicade®) Î·È ada- Û˘-1 Û ÂÓÂÚÁfi ηۿÛË-1. ªÂ ÙË ÛÂÈÚ¿ Ù˘, Ë Î·- limumab (Humira®), ηıÒ˜ Î·È Ô ·ÓÙ·ÁˆÓÈÛÙ‹˜ ÙÔ˘ Û¿ÛË-1 ÂÓÂÚÁÔÔÈ› ÙËÓ ÚÔ-IL-1‚ Û ÂÓÂÚÁfi IL- ˘Ô‰Ô¯¤· Ù˘ IL-1‚ anakinra (Kineret®)11,32. ¶ÂÚÈÛÛfi- 1‚, ̤ۈ ÙÔ˘ ÔÏ˘ÌÂÚÈÛÌÔ‡ (ÔÚÁ¿ÓˆÛË Û ÙÚÈÌÂ- ÙÂÚ˜ ÌÂϤÙ˜ Ì ÔÏ˘ÏËı¤ÛÙÂÚ˜ ÔÌ¿‰Â˜ Ú¤ÂÈ Ó· Ú¤˜) ÙÔ˘ ASC, Ì ·ÔÙ¤ÏÂÛÌ· ÙË ÊÏÂÁÌÔÓÒ‰Ë ‰ÈÂÚ- ‰ÈÂÍ·¯ıÔ‡Ó ÒÛÙ ӷ ÂÍ¿ÁÔ˘Ì ·ÛʷϤÛÙÂÚ· Û˘ÌÂ- Á·Û›·17,27. ΔÔ ·Ó ÙÔ Û‡ÌÏÔÎÔ ASC-˘Ú›ÓË ‰ËÌÈ- Ú¿ÛÌ·Ù· ÁÈ· ÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Î·È ÙËÓ ·ÛÊ¿- Ô˘ÚÁ› ¤Ó· ȉȷ›ÙÂÚÔ ÊÏÂÁÌÔÓfiۈ̷, ·ÚfiÌÔÈÔ Ì ÏÂÈ· ÙˆÓ Ó¤ˆÓ ·˘ÙÒÓ ·Ú·ÁfiÓÙˆÓ. ·˘Ùfi Ù˘ ÎÚ˘Ô˘Ú›Ó˘, ‹ ·Ó Ë ˘Ú›ÓË ·ÓÙ·ÁˆÓ›˙ÂÙ·È ¿ÌÂÛ· ÙËÓ ÎÚ˘Ô˘Ú›ÓË ˆ˜ ÚÔ˜ ÙË Û‡Ó‰ÂÛË Ì ÙÔÓ Abstract ASC ‹ ·Ó ˘¿Ú¯ÂÈ ¿ÏÏÔ ¤ÌÌÂÛÔ Â›Â‰Ô Ú‡ıÌÈÛ˘, ªitroulis G, Papadopoulos V. Anosia 2009; 1: 49-56. ‰ÂÓ ¤¯ÂÈ Ï‹Úˆ˜ ‰È¢ÎÚÈÓÈÛÙ›. There is an ongoing interest regarding autoinflammation, namely Á) °ÂÓÂÙÈΤ˜ ‚Ï¿‚˜ Û ¿ÏÏ· ›‰· ÏËÓ the result of the unreasoned stimulation of the innate immunity ÙÔ˘ MEFV Î·È ÙÔ˘ CIAS1/ NALP3 in the absence of autoantibodies and T-autoreactive cells. The discrimination between different clinical entities involving autoim- ™ÙËÓ ÂÚ›ÙˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ƒ∞ƒ∞, Ì›·˜ ÎÏÈÓÈ΋˜ munity enabled the determination of the subsequent genetic de- ÔÓÙfiÙËÙ·˜ Ô˘ Û˘ÌÂÚÈÏ·Ì‚¿ÓÂÈ Á·ÁÁÚ·ÈÓ҉˜ ˘fi- fects and thus elucidated the underlying molecular pathways. The ‰ÂÚÌ·, ÛÔ‚·ÚÔ‡ ‚·ıÌÔ‡ ΢ÛÙÈ΋ ·ÎÌ‹ Î·È ÈÓÛÔ˘ÏÈ- present review concerns with the presentation of the current ÓÔÂÍ·ÚÙÒÌÂÓÔ Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË Ì ηı˘ÛÙÂÚË- knowledge and the ongoing concerns in the research field. ̤ÓË ¤Ó·ÚÍË, ‰È·ÈÛÙÒıËΠ‚Ï¿‚Ë ÛÙÔ ÁÔÓ›‰ÈÔ Key words: Autoinflammation, Familial Mediterranean fever, inter- PSTPIP1. ΔÔ ÁÔÓ›‰ÈÔ ·˘Ùfi Έ‰ÈÎÔÔÈ› ÁÈ· ÙËÓ Úˆ- leukin-1‚. Ù½ÓË PSTPIP1 (proline-serine-threonine phosphatase- interacting protein 1), Ë ÔÔ›·, ÛÙË ÌÂÙ·ÏÏ·Á̤ÓË Ù˘ BÈ‚ÏÈÔÁÚ·Ê›· ÌÔÚÊ‹, ˘ÂÚʈÛÊÔÚ˘ÏÈÒÓÂÙ·È. ∫·ıÒ˜ Ë PSTPIP1 Û˘Ó‰¤ÂÙ·È Ì ÙËÓ ˘Ú›ÓË, ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙËÓ PSTPIP1 1. Kastner DL. Hereditary periodic fever syndromes. Hema- tology Am Soc Hematol Educ Program 2005; 74-81. ÌÂÈÒÓÔ˘Ó ÙË Ú˘ıÌÈÛÙÈ΋ ÈηÓfiÙËÙ· Ù˘ ˘Ú›Ó˘ ˆ˜ 29 2. McDermott MF, Tschopp J. From autoinflammation to ÚÔ˜ ÙËÓ ·Ú·ÁˆÁ‹ IL-1‚ . fevers, crystals and hypertension: how basic research ex- ΔÔ Û‡Ó‰ÚÔÌÔ Majeed, Ô˘ ÂÌÊ·Ó›˙ÂÙ·È ˆ˜ Ô- plains inflammatory diseases. Trends Mol Med 2007; Ï˘ÂÛÙȷ΋ ÔÛÙÂÔÌ˘ÂÏ›Ùȉ·, Û˘ÁÁÂÓ‹˜ ‰˘ÛÂÚ˘ıÚÔÔÈ- 13(9): 381-8. ËÙÈ΋ ·Ó·ÈÌ›· Î·È ÊÏÂÁÌÔÓ¤˜ ‰¤ÚÌ·ÙÔ˜, ÚÔηÏÂ›Ù·È 3. Matzinger P. The danger model: a renewed sence of self. ·fi ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ ÁÔÓ›‰ÈÔ LPIN2. H CRMO, Ô˘ Science 2002; 296(5566): 304301-5. Û˘ÌÌÂÚ›˙ÂÙ·È ÙËÓ ÔÏ˘ÂÛÙȷ΋ ÔÛÙÂÔÌ˘ÂÏ›Ùȉ·, ·ÏÏ¿ 4. McGonagle, D, McDermott MF. A proposed classification of the immunological diseases. PLOS medicine 2006; 3(8): ‰ÂÓÓ Û˘Óԉ‡ÂÙ·È ·fi ·Ó·ÈÌ›· Î·È ‰ÂÚÌ·ÙÈΤ˜ ÂΉË- 1242-8e297. ÏÒÛÂȘ, ʤÚÂÈ ¿ÏÏ· ÁÂÓÂÙÈο ¯·Ú·ÎÙËÚÈÛÙÈο: ÌÂÙ·Ï- 5. Mitroulis I, Papadopoulos VP, Konstantinidis T, Ritis K. Ï¿ÍÂȘ ÛÙÔ ÁÔÓ›‰ÈÔ PSTPIP230. Anakinra suppresses familial Mediterranean fever crises 56 ™˘ÛÙËÌ·ÙÈο ·˘ÙÔÊÏÂÁÌÔÓÒ‰Ë ÓÔÛ‹Ì·Ù·
in a colchicine-resistant patient. Neth J Med 2008; 19. Δunca M. Ozdogan H. Molecular and genetic characteri- 66(11): 489-91. stics of hereditary autoinflammatory diseases. Curr Drug 6. Konstantopoulos K, Kanta A, Deltas C, et al. Familial Medi- Targ 2005; 4(1): 77-80. terranean fever associated pyrin mutations in Greece. 20. French FMF. Consortium. A candidate gene for familial Me- Ann Rheum Dis 2003; 62(5): 479-481. diterranean fever. Nat Genet 1997; 17(1): 25-31. 7. Ritis K, Giaglis S, Spathari N, et al. Non-isotopic RNase clea- 21. Centola M, Chen X, Sood R, et al. Construction of an ap- vage assay for mutation detection in MEFV, the gene re- proximately 700-kb transcript map around the familial sponsible for familial Mediterranean fever, in a cohort of Mediterranean fever locus on human chromosome 16p Greek patients. Ann Rheum Dis 2004; 63(4): 438-443. 13.3. Genome Res 1998; 8(11): 1172-91. 8. Giaglis S, Papadopoulos V, Kambas K, et al. MEFV alterations 22. Papin S, Cuenin S, Agostini L, et al. The SPRY domain of Py- and population genetics analysis in a large cohort of rin, mutated in familial Mediterranean fever patients, inte- Greek patients with familial Mediterranean fever. Clin racts with inflammasome components and inhibits proIL- Genet 2007; 71(5): 458-467. 1beta processing. Cell Death Differ 2007; 14(8): 1457-66. 9. Masson C, Simon V, Hoppé E, Insalaco P, Cissé I, Audran M. 23. Papadopoulos VP, Giaglis S, Mitroulis I, Ritis K. The po- Tumor necrosis factor receptor-associated periodic syn- pulation genetics of familial mediterranean fever: a meta- drome (TRAPS): definition, semiology, prognosis, patho- analysis study. Ann Hum Genet 2008; 72(Pt 6): 752-761. genesis, treatment, and place relative to other periodic 24. Giaglis S, Mimidis K, Papadopoulos V, et al. Increased fre- joint diseases. Joint Bone Spine. 2004; 71(4): 284-90. quency of mutations in the gene responsible for familial 10. Kastner DL, Aksentijevich I. Intermittent and periodic ar- Mediterranean fever (MEFV) in a cohort of patients with thritis syndromes. In: Koopman WJ, Moreland LW, eds. ulcerative colitis: evidence for a potential disease- Arthritis and Allied Conditions (15th ed). Philadelphia: modifying effect? Dig Dis Sci 2006; 51(4): 687-92. Lippincott Williams and Wilkins; 2005: 1411-61. 25. Cattan D. MEFV mutation carriers and diseases other than 11. Church LD, Churchman SM, Hawkins PN, McDermott MF. familial Mediterranean fever: Proved and non-proved as- Hereditary auto-inflammatory disorders and biologics. sociations; putative biological advantage. Curr Drug Targ Springer Semin Immun 2006; 27(4): 494-508. 2005; 4(1): 105-12. 12. Scolozzi R, Boccafogli A, Vicentini L. Hyper-IgD syndrome 26. Stehlic Stehlik C. Reed JC. The pyrin connection: Novel and other hereditary periodic fever syndromes. Reuma- players in innate immunity and inflammation. J Exp Med tismo 2004; 56(3): 147-55. 2004; 200(5): 551-8. 13. Van der Hilst JC, Bodar EJ, Barron KS, et al. Long-term fol- 27. Yu JW, Wu J, Zhang Z, et al. Cryopyrin and pyrin activate low-up, clinical features, and quality of life in a series of caspase-1, but not NF-kappaB, via ASC oligomerization. 103 patients with hyperimmunoglobulinemia D syndro- Cell Death Differ 2006; 13(2): 236-49. me. Medicine (Baltimore) 2008; 87(6): 301-10. 28. Chae JJ, Wood G, Richard K, Jaffe H, Colburn NT, Masters 14. Cailliez M, Garaix F, Rousset-Rouvière C, et al. Anakinra is SL, Gumucio DL, Shoham NG, Kastner DL, et al. The safe and effective in controlling hyperimmunoglobulinae- familial Mediterranean fever protein, pyrin, is cleaved by mia D syndrome-associated febrile crisis. J Inherit Metab caspase-1 and activates NF-kappaB through its N-ter- Dis 2006; 29(6): 763. minal fragment. Blood 2008; 112(5): 1794-803. 15. Ramos E, Arfistegui JI, Campuzano S, Rius J, Bousoño C, 29. Arfistegui JI, Yagüe J. Hereditary systemic autoinflamma- Yagüe J. Positive clinical and biochemical responses to tory diseases. Part II: cryopyrin-associated periodic syn- anakinra in a 3-yr-old patient with cryopyrin-associated dromes, pediatric systemic granulomatosis and PAPA periodic syndrome (CAPS). Rheumatology (Oxford) syndrome. Med Clin (Barc) 2008; 130(11): 429-38. 2005 Aug; 44(8): 1072-3. 30. El-Shanti HI, Ferguson PJ. Chronic recurrent multifocal 16. Church LD, McDermott MF. Canakinumab, a fully-human osteomyelitis: a concise review and genetic update. Clin mAb against IL-1beta for the potential treatment of in- Orthop Relat Res 2007; 462: 11-9. flammatory disorders. Curr Opin Mol Ther 2009; 11(1): 31. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and 81-9. innate immunity. Cell 2006; 124(4): 783-801. 17. ªartinon F, Burns K, Tschopp J. The inflammasome: a mo- 32. Gattorno M. Diagnosis and management of autoinflamma- lecular platform triggering activation of inflammatory cas- tory diseases in childhood. J Clin Immunol 2008; 28 pases and processing of proIL-1‚. Mol Cell 2002; 10(2): (Suppl 1): S73-S83. 417-26. 18. ªartinon F. Tschopp J. Inflammatory caspases: Linking an intracellular innate immune system to autoinflammatory ∞ÏÏËÏÔÁÚ·Ê›·: diseases. Cell 2004; 117(5): 561-74. E-mail: [email protected] ∞Ó·ÛÎfiËÛË
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¶ÔÏ˘¿ÚÈı̘ ÂȉËÌÈÔÏÔÁÈΤ˜ ¤Ú¢Ó˜ ·ÏÏ¿ Î·È ÂÈÚ·Ì·ÙÈΤ˜ ÌÂϤÙ˜ ˘Ô‰ÂÈÎÓ‡Ô˘Ó fiÙÈ Ë ‰È·‰Èηۛ· Ù˘ ·ıËڈ̿وÛ˘ ·ÔÙÂ- Ï› ÙË ÊÏÂÁÌÔÓÒ‰Ë ·¿ÓÙËÛË Û ϋıÔ˜ ‚Ï·ÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ, ÌÂٷ͇ ÙˆÓ ÔÔ›ˆÓ Ë ·ÚÙËÚȷ΋ ˘¤ÚÙ·ÛË Î·È Ô Û·Î¯·Ú҉˘ ‰È·‚‹Ù˘. ∏ ‡·ÚÍË ˘¤ÚÙ·Û˘ Î·È ‰È·‚‹ÙË ·˘Í¿ÓÂÈ ÛËÌ·ÓÙÈο ÙË ÓÔÛËÚfiÙËÙ· Î·È ÙË ıÓËÙfiÙËÙ· ·fi ηډȷÁÁÂȷ΋ ÓfiÛÔ. ™ÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜ Â›Ó·È ·˘ÍË̤ÓË ÙfiÛÔ Ë ÈÛÙÈ΋ ¤ÎÊÚ·ÛË fiÛÔ Î·È ÔÈ Û˘ÁÎÂÓÙÚÒÛÂȘ ÛÙÔ Ï¿ÛÌ· ÙˆÓ ‰ÂÈÎÙÒÓ Ù˘ ÊÏÂÁÌÔÓ‹˜. ªÔÏÔ- ÓfiÙÈ ÔÏϤ˜ ΢ÙÙ·ÚÔΛÓ˜, ÚˆÙ½Ó˜ ÔÍ›·˜ Ê¿Û˘, ÌfiÚÈ· ÚÔÛÎfiÏÏËÛ˘, ÊÏÂÁÌÔÓÒ‰Ë ÂÚÂı›ÛÌ·Ù· ÌÔÚÔ‡Ó Ó· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó ˆ˜ ‰Â›ÎÙ˜ ÛÙË ‰È¿ÁÓˆÛË Î·È ÙËÓ ÚfiÁÓˆÛË Ù˘ ÂͤÏÈ͢ Ù˘ ÊÏÂÁÌÔÓ‹˜, ˆÛÙfiÛÔ ˘¿Ú¯Ô˘Ó Û˘ÁÎÂÎÚÈ̤ÓÔÈ ÂÚÈÔÚÈÛÌÔ› Ô˘ ·ÊÔ- ÚÔ‡Ó ÙËÓ Â˘·ÈÛıËÛ›· Î·È ÙËÓ ÂȉÈÎfiÙËÙ¿ ÙÔ˘˜, ηıÒ˜ Î·È ÙËÓ ·ÎÚ›‚ÂÈ· Î·È ÛÙ·ıÂÚfiÙËÙ· Ù˘ ÌÂıfi‰Ô˘ ̤ÙÚËÛ‹˜ ÙÔ˘˜ ÛÙËÓ ÎÏÈÓÈ΋ Ú¿- ÍË. ªÂ ‚¿ÛË Ù· ˘¿Ú¯ÔÓÙ· ‰Â‰Ô̤ӷ ÌfiÓÔ Ë hs-CRP ÌÔÚ› Ó· ·ÔÙÂϤÛÂÈ ·ÍÈfiÈÛÙÔ ‰Â›ÎÙË Î·Ú‰È·ÁÁÂÈ·ÎÔ‡ ÎÈÓ‰‡ÓÔ˘.
§¤ÍÂȘ-ÎÏÂȉȿ: ۷ί·Ú҉˘ ‰È·‚‹Ù˘, ·ÚÙËÚȷ΋ ˘¤ÚÙ·ÛË, C-·ÓÙȉÚÒÛ· ÚˆÙ½ÓË.
∂ÈÛ·ÁˆÁ‹ ∏ Û˘¯ÓfiÙËÙ· Ù˘ ˘¤ÚÙ·Û˘ ÛÙÔÓ ÁÂÓÈÎfi ÏËı˘ÛÌfi, ·˘ÙÔ‡˜ Ì ˘„ËÏfi ΛӉ˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ηډȷÁÁÂÈ·ÎÒÓ Û‡Ìʈӷ Ì ÙȘ ÙÂÏÂ˘Ù·›Â˜ ÌÂÙÚ‹ÛÂȘ, ÍÂÂÚÓ¿ ÙÔ Û˘Ì‚·Ì¿ÙˆÓ. ¶Ú¿ÁÌ·ÙÈ, Ë ‡·ÚÍË ‰È·‚‹ÙË ÛÙÔ˘˜ ˘- 25%, ÂÓÒ ÛÙȘ ËÏÈ˘ ¿Óˆ ÙˆÓ 60 ÂÙÒÓ ¤Ó·˜ ÛÙÔ˘˜ ÂÚÙ·ÛÈÎÔ‡˜ ‰ÈÏ·ÛÈ¿˙ÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ηÚ- ‰‡Ô Â›Ó·È ˘ÂÚÙ·ÛÈÎfi˜. ∞fi ÙËÓ ¿ÏÏË, Ë Û˘¯ÓfiÙËÙ· ‰È·ÁÁÂÈ·ÎÔ‡ ÂÂÈÛÔ‰›Ô˘2. ™ÙÔ˘˜ ·ÛıÂÓ›˜ Ì ‰È·‚‹ÙË ÙÔ˘ ۷ί·ÚÒ‰Ô˘˜ ‰È·‚‹ÙË ·˘Í¿ÓÂÙ·È Ú·Á‰·›·, ȉȷ›- Ù‡Ô˘ 2 Î·È ˘¤ÚÙ·ÛË Ë Î·Ú‰È·ÁÁÂȷ΋ ÓfiÛÔ˜ Â›Ó·È ÙÂÚ· ÛÙȘ ·Ó·Ù˘ÛÛfiÌÂÓ˜ ¯ÒÚ˜. ∏ ˘¤ÚÙ·ÛË Û˘- ÔÏ˘·Ú·ÁÔÓÙÈ΋ Î·È Ë Û˘Ó˘¿Ú¯Ô˘Û· ÂÓ‰ÔıËÏȷ΋ ¯Ó¿ Û˘Ó˘¿Ú¯ÂÈ Ì ÙÔÓ ‰È·‚‹ÙË, ¤ÙÛÈ, ÙÔ 60% ÙˆÓ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·, ·ÁÁÂȷ΋ ÊÏÂÁÌÔÓ‹ Î·È Ë ·˘ÍË̤ÓË ‰È·‚ËÙÈÎÒÓ Â›Ó·È ˘ÂÚÙ·ÛÈÎÔ› Î·È ¿Óˆ ·fi ÙÔ 20% ÏÂ˘ÎˆÌ·ÙÔ˘Ú›· Ì ÙËÓ ¿ÚÔ‰Ô ÙÔ˘ ¯ÚfiÓÔ˘ Â›Ó·È ·- ÙˆÓ ·ÛıÂÓÒÓ Ì ˘¤ÚÙ·ÛË Â›Ó·È ‰È·‚ËÙÈÎÔ›1. √È ÓÂÍ¿ÚÙËÙÔÈ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ·˘ÍË̤Ó˘ ıÓËÙfi- ·ÛıÂÓ›˜ Ì ˘¤ÚÙ·ÛË Î·È ‰È·‚‹ÙË Î·Ù·Ù¿ÛÛÔÓÙ·È Û ÙËÙ·˜3. 58 ∞ÁÁÂȷ΋ ÊÏÂÁÌÔÓ‹ ÛÙËÓ ˘¤ÚÙ·ÛË Î·È ÙÔÓ Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË
ºÏÂÁÌÔÓ‹ ÛÙËÓ ˘¤ÚÙ·ÛË Î·È ÙÔÓ ÛÙÈÎfi ÚfiÏÔ ÛÙËÓ ·ıÔÁ¤ÓÂÛ‹ Ù˘10 Î·È Ô˘ Û˘ÌÌÂÙ¤- ‰È·‚‹ÙË ¯Ô˘Ó ÛÙËÓ ·ıÔÊ˘ÛÈÔÏÔÁ›· ·ÁÁÂȷ΋˜ ‚Ï¿‚˘ Î·È ¿Ï- ÏˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ ·Ú·ÁfiÓÙˆÓ fiˆ˜ Ô Û·Î¯·ÚÒ- √ ÚfiÏÔ˜ Ù˘ ÊÏÂÁÌÔÓ‹˜ ¤¯ÂÈ Î·ıÈÂÚˆı› ÙËÓ ÚÔË- ‰Ë˜ ‰È·‚‹Ù˘11. ¶Ú¿ÁÌ·ÙÈ, Ë ÊÏÂÁÌÔÓ‹ ·Ó·ÁÓˆÚ›˙Â- ÁÔ‡ÌÂÓË ‰ÂηÂÙ›· ÛÙË ‰È·‰Èηۛ· Ù˘ ·ıËڈ̷ÙÈ΋˜ Ù·È Û‹ÌÂÚ· ˆ˜ Ô ÎÂÓÙÚÈÎfi˜ Ì˯·ÓÈÛÌfi˜ Ô˘ Û˘Ì‚¿Ï- 4 ‚Ï¿‚˘ . ŒÙÛÈ, ·fi ·ıÔÏÔÁÔ·Ó·ÙÔÌÈ΋˜ ÛÎÔÈ¿˜, ÏÂÈ ÛÙËÓ ÂͤÏÈÍË Ù˘ ηډȷÁÁÂȷ΋˜ ÓfiÛÔ˘ ÁÂÓÈο, fiÏ· Ù· ÛÙ¿‰È·, ·fi ÙËÓ ¤Ó·ÚÍË, ÙËÓ ·Ó¿Ù˘ÍË Î·È ÙȘ Î·È Èı·ÓfiÓ ÂÓ¤¯ÂÙ·È ÛÙËÓ ˘ÚÔ‰fiÙËÛË Ù˘ ÈÛ¯·ÈÌ›·˜ ÂÈÏÔΤ˜ Ù˘ ·ıËڈ̷ÙÈ΋˜ Ͽη˜, ÌÔÚ› Ó· ıÂ- Î·È ÙÔ˘ ÂÌÊÚ¿ÁÌ·ÙÔ˜ ÙÔ˘ Ì˘Ôηډ›Ô˘12. ™ÙÔ˘˜ ˆÚËıÔ‡Ó ÊÏÂÁÌÔÓ҉˘ ·¿ÓÙËÛË Û ‚Ï·ÙÈÎÔ‡˜ ·- ·ÛıÂÓ›˜ Ì ηډȷÁÁÂȷ΋ ÓfiÛÔ Â›Ó·È ·˘ÍË̤ÓË Ùfi- Ú¿ÁÔÓÙ˜, fiˆ˜ Ë ˘¤ÚÙ·ÛË Î·È Ô ‰È·‚‹Ù˘. ∏ ȉÈÔ- ÛÔ Ë ÈÛÙÈ΋ ¤ÎÊÚ·ÛË fiÛÔ Î·È Û˘ÁÎÂÓÙÚÒÛÂȘ ÛÙÔ ·ı‹˜ ˘¤ÚÙ·ÛË ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ·˘ÍË̤ÓË ÂÚÈ- Ï¿ÛÌ· ÙˆÓ ‰ÂÈÎÙÒÓ Ù˘ ÊÏÂÁÌÔÓ‹˜13. ™Ù· ÌfiÚÈ· ·˘- ÊÂÚÈ΋ ·ÓÙ›ÛÙ·ÛË ÛÙË ÚÔ‹ ÙÔ˘ ·›Ì·ÙÔ˜. ∏ ·ÓÙ›ÛÙ·ÛË Ù¿ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È Ë C-·ÓÙȉÚÒÛ· ÚˆÙ½ÓË (CRP), ·˘Ù‹ ÚÔ¤Ú¯ÂÙ·È Î˘Ú›ˆ˜ ·fi ÙËÓ ›ÂÛË Ô˘ ·ÛΛٷÈ, Ù· ÌfiÚÈ· ÚÔÛÎfiÏÏËÛ˘ fiˆ˜ ÙˆÓ ·ÁÁÂÈ·ÎÒÓ Î˘ÙÙ¿- ÙË ÏÂÁfiÌÂÓË ‰È·ÙÌËÙÈ΋ Ù¿ÛË, ÛÙȘ ÌÈÎÚ¤˜ ·ÚÙËڛ˜ ÚˆÓ (vascular cell adhesion molecule-1, VCAM-1) Î·È Î·È Ù· ·ÚÙËÚÈfiÏÈ·, Ô˘ ·ÔηÏÔ‡ÓÙ·È Î·È ·ÚÙËڛ˜ ÙÔ ÂÓ‰Ô΢ÙÙ¿ÚÈÔ (intracellular adhesion molecule-1, 5 ·ÓÙ›ÛÙ·Û˘ . √È ·ÚÙËڛ˜ ·ÓÙ›ÛÙ·Û˘ ‰È·‰Ú·Ì·Ù›- ICAM-1), ΢ÙÙ·ÚÔΛÓ˜ fiˆ˜ Ë ¯ËÌÂÈÔÙ·ÎÙÈ΋ Úˆ- ˙Ô˘Ó Èı·ÓfiÓ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÙfiÛÔ ÛÙËÓ ·Ó¿Ù˘ÍË Ù½ÓË ÙˆÓ ÌÔÓÔ΢ÙÙ¿ÚˆÓ (monocyte chemoattractant Ù˘ ˘¤ÚÙ·Û˘ fiÛÔ Î·È ÛÙË ‰ËÌÈÔ˘ÚÁ›· ÙˆÓ ÂÈÏÔ- protein-1, MCP-1), ηıÒ˜ Î·È ·ÓÙÈ-ÈÓˆ‰ÔÏ˘ÙÈÎÔ› ·- 6,7 ÎÒÓ Ù˘ . ªÈÎÚ¤˜ ÌÂÈÒÛÂȘ ÙÔ˘ ·˘ÏÔ‡ ÙˆÓ ÌÈÎÚÒÓ Ú¿ÁÔÓÙ˜ fiˆ˜ Ô ·Ó·ÛÙÔϤ·˜ ÙÔ˘ ÂÓÂÚÁÔÔÈËÙ‹ ÙÔ˘ ·ÚÙËÚÈÒÓ ·˘Í¿ÓÔ˘Ó ÛËÌ·ÓÙÈο ÙËÓ ·ÓÙ›ÛÙ·ÛË. ™ÙËÓ Ï·ÛÌÈÓÔÁfiÓÔ˘ (plasminogen activator inhibitor-1, ˘¤ÚÙ·ÛË, ÔÈ ·ÚÙËڛ˜ ·ÓÙ›ÛÙ·Û˘ ˘Ê›ÛÙ·ÓÙ·È ·ÁÁÂÈ- PAI-1). ™Â ÂÈÚ·Ì·ÙÈΤ˜ ˘ÂÚÙ¿ÛÂȘ ¤¯ÂÈ ·Ô‰Âȯı› ·Î‹ ·Ó·‰È·ÌfiÚʈÛË (vascular remodeling) Ô˘ Û˘Ó›- ·˘ÍË̤ÓË Ú‡ıÌÈÛË ÙˆÓ ÈÛÙÈÎÒÓ ‰È·‚È‚·ÛÙÒÓ Ù˘ ÛÙ·Ù·È ÛÙÔÓ ÂÚÈÔÚÈÛÌfi ÙÔ˘ ·˘ÏÔ‡ Î·È ÙËÓ ¿¯˘ÓÛË ÊÏÂÁÌÔÓ‹˜, fiˆ˜ ÙÔ˘ ˘ÚËÓÈÎÔ‡ ·Ú¿ÁÔÓÙ· Îμ (nu- ÙÔ˘ ̤ÛÔ˘ ¯ÈÙÒÓ·, Ë ÔÔ›· ÌÔÚ› Ó· Â›Ó·È ‰ÔÌÈ΋, clear factor-Îμ, NF-Îμ), Ë ÚˆÙ½ÓË ÂÓÂÚÁÔÔÈËÙ‹˜ Ì˯·ÓÈ΋ ‹ ÏÂÈÙÔ˘ÚÁÈ΋. ™ÙËÓ ·ÁÁÂȷ΋ ·˘Ù‹ ·Ó·‰È·- (activator protein-1, AP-1), Ù· ÌfiÚÈ· ÚÔÛÎfiÏÏËÛ˘ ÌfiÚʈÛË ÂÌϤÎÔÓÙ·È Î·ıÔÚÈÛÙÈο Ë ·˘ÍË̤ÓË ÂÓ·- (VCAM-1, ICAM-1, platelet endothelial cell adhesion fiıÂÛË ÂÍˆÎ˘ÙÙ¿ÚÈ·˜ ıÂ̤ÏÈ·˜ Ô˘Û›·˜ Î·È Ë ÊÏÂÁÌÔ- molecule) Î·È Ô ÈÛÙÈÎfi˜ ·Ú¿ÁˆÓ13-17. Ó‹. ∏ ¯ÚfiÓÈ· ·ÁÁÂÈÔÛ‡Û·ÛË ÙˆÓ ·ÁÁ›ˆÓ, Ô˘ ÔÊ›- ÏÂÙ·È ÛÙËÓ Â›‰Ú·ÛË ÙÔ˘ ·˘ÍË̤ÓÔ˘ ·ÁÁÂÈ·ÎÔ‡ Ùfi- ΔÔ Û‡ÛÙËÌ· ÚÂÓ›Ó˘-·ÁÁÂÈÔÙÂÓÛ›Ó˘- ÓÔ˘, ÛÙÔ Û‡ÛÙËÌ· ÚÂÓ›Ó˘-·ÁÁÂÈÔÙÂÓÛ›Ó˘-·Ï‰ÔÛÙÂ- ·Ï‰ÔÛÙÂÚfiÓ˘: Ô ÛËÌ·ÓÙÈÎfiÙÂÚÔ˜ ÚfiÓ˘ (RAAS), ÛÙȘ ηÙ¯ÔϷ̛Ә Î·È Û ·˘ÍËÙÈÎÔ‡˜ Ì˯·ÓÈÛÌfi˜ Ù˘ ·ÁÁÂȷ΋˜ ‚Ï¿‚˘ ·Ú¿ÁÔÓÙ˜, ÌÔÚ› Ó· Ù· ·Áȉ‡ÛÂÈ ÏfiÁˆ Ù˘ ·Ó·- ‰È·ÌfiÚʈۋ˜ ÙÔ˘˜ ·fi ÙËÓ ·˘ÍË̤ÓË ·Ú·ÁˆÁ‹ Ù˘ ∏ ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ ™˘ÛÙ‹Ì·ÙÔ˜ ƒÂÓ›Ó˘-∞ÁÁÂÈÔÙÂÓ- ÂÍˆÎ˘ÙÙ¿ÚÈ·˜ ıÂ̤ÏÈ·˜ Ô˘Û›·˜, Û ÌfiÓÈÌË Î·È ÌË ·Ó·- Û›Ó˘-∞ωÔÛÙÂÚfiÓ˘ (™ƒ∞∞) ¤¯ÂÈ ÚfiÏÔ-ÎÏÂȉ› ÛÙËÓ ÛÙÚ¤„ÈÌË ·ÁÁÂÈÔÛ‡Û·ÛË8. ·Ó¿Ù˘ÍË Î·È ÛÙËÓ ·ıÔÊ˘ÛÈÔÏÔÁ›· Ù˘ ηډȷÁÁÂÈ·- ∏ ÌÂÌÔӈ̤ÓË Û˘ÛÙÔÏÈ΋ ˘¤ÚÙ·ÛË ÙˆÓ ËÏÈÎȈ- ΋˜ ÓfiÛÔ˘18. ∏ ·ÁÁÂÈÔÙÂÓÛ›ÓË ππ, ¤Ó· ÙÂÏÈÎfi ÚÔ˚fiÓ Ì¤ÓˆÓ ÔÊ›ÏÂÙ·È ÛÙË ÏfiÁˆ Ù˘ ËÏÈΛ·˜ ·ÁÁÂȷ΋ ‰˘- Î·È Î‡ÚÈÔ˜ ‰È·‚È‚·ÛÙ‹˜ ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜, ÂÓÂÚÁÔÔÈ› Ûη̄›· Î·È ÛÙËÓ ÂÚÈÔÚÈṲ̂ÓË ·ÁÁÂÈÔ¯·Ï·ÛÙÈ΋ ÏÂÈ¿‰· Ì˯·ÓÈÛÌÒÓ Ô˘ Ô‰ËÁÔ‡Ó ÛÙËÓ ·ÁÁÂȷ΋ ·¿ÓÙËÛË ÙˆÓ ·ÁÁ›ˆÓ9. ∏ ·ÚÙËÚȷ΋ ‰˘Ûη̄›· ·˘- ·Ó·‰È·ÌfiÚʈÛË Î·È ·ÁÁÂȷ΋ ‚Ï¿‚Ë. ™’ ·˘Ù¤˜ ÂÚÈ- Í¿ÓÂÙ·È Ì ÙËÓ ÚfiÔ‰Ô Ù˘ ËÏÈΛ·˜ Î·È ÙË Û˘Ó‡·ÚÍË Ï·Ì‚¿ÓÔÓÙ·È Ë ·ÁÁÂÈÔÛ‡Û·ÛË, Ë ·‡ÍËÛË ÙˆÓ Î˘ÙÙ¿- Î·È ¿ÏÏˆÓ ·Ú·ÁfiÓÙˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÔ‡ ÎÈÓ‰‡ÓÔ˘, ÚˆÓ, Ë Â·ÁˆÁ‹ ÔÍÂȉˆÙÈÎÔ‡ stress Î·È Ë ÊÏÂÁÌÔÓ‹ fiˆ˜ Ë ˘¤ÚÙ·ÛË, Ô Û·Î¯·Ú҉˘ ‰È·‚‹Ù˘, Ë ‰˘ÛÏÈ- (™¯. 1). ∏ ·ÁÁÂÈÔÙÂÓÛ›ÓË ππ ηْ ·Ú¯¿˜ ÂÌϤÎÂÙ·È ÛÙË È‰·ÈÌ›·, Ë ·¯˘Û·ÚΛ· Î·È ÙÔ Î¿ÓÈÛÌ·. √È ·ÎÚȂ›˜ ÚÔÊÏÂÁÌÔÓÒ‰Ë ‰È·‰Èηۛ· ÙÚÔÔÔÈÒÓÙ·˜ ÙËÓ ·Â- Ì˯·ÓÈÛÌÔ› Ù˘ ·ÚÙËÚȷ΋˜ ‰˘Ûη̄›·˜ ›Ù ÏfiÁˆ Ï¢ı¤ÚˆÛË Î˘ÙÙ·ÚÔÎÈÓÒÓ19 Î·È ÙˆÓ ÚÔ-ÊÏÂÁÌÔÓˆ- ËÏÈΛ·˜ ›Ù ÏfiÁˆ ·ıÔÏÔÁÈÎÒÓ Î·Ù·ÛÙ¿ÛÂˆÓ ‰ÂÓ ‰ÒÓ ÌÂÙ·ÁÚ·ÊÈÎÒÓ ·Ú·ÁfiÓÙˆÓ, fiˆ˜ ÙÔ˘ NF-Îμ20, ¤¯Ô˘Ó Ï‹Úˆ˜ ‰È¢ÎÚÈÓÈÛı›. Ô ÔÔ›Ô˜ Ì ÙË ÛÂÈÚ¿ ÙÔ˘ Ú˘ıÌ›˙ÂÈ ÙËÓ ¤ÎÊÚ·ÛË ÙˆÓ Δ· ·˘ÍË̤ӷ ›‰· ·ÚÙËÚȷ΋˜ ›ÂÛ˘ ÌÔ- ÌÔÚ›ˆÓ ÚÔÛÎfiÏÏËÛ˘ (ICAM-1 Î·È VCAM-1)18,21. ÚÔ‡Ó Ó· ÚÔηϤÛÔ˘Ó ÚÔ-ÊÏÂÁÌÔÓÒ‰Ë ·¿ÓÙËÛË. ŸÏ· Ù· ·Ú·¿Óˆ ÌÔÚÔ‡Ó Ó· ÚÔηϤÛÔ˘Ó ÊÏÂÁ- ∏ ˘¤ÚÙ·ÛË ÂÈÙ›ÓÂÈ ÙËÓ ÂͤÏÈÍË Ù˘ ·ıËÚÔÛÎÏ‹Úˆ- ÌÔÓ‹ ̤۷ ÛÙÔ ·ÁÁÂÈ·Îfi ÙÔ›¯ˆÌ·, Ì ·ÎfiÏÔ˘ıË Û˘ Ë ÔÔ›· ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÙËÓ ·ÚÔ˘Û›· ÚÔ- ÂÓ·fiıÂÛË ÂÍˆÎ˘ÙÙ¿ÚÈ·˜ ıÂ̤ÏÈ·˜ Ô˘Û›·˜ Î·È ˘ÂÚ- ÊÏÂÁÌÔÓˆ‰ÒÓ ÌÔÚ›ˆÓ Ô˘ ‰È·‰Ú·Ì·Ù›˙Ô˘Ó Î·ıÔÚÈ- ÙÚÔÊ›· ηÈ/‹ ˘ÂÚÏ·Û›· ÙˆÓ Ï›ˆÓ Ì˘˚ÎÒÓ Î˘ÙÙ¿- ∫. ¶·Ï¤Ù·˜ 59
BP Λεμφοκύτταρα IL-6, TNFα, MCP-1 VCAM-1, ICAM-1 PAI-1 ET CAM ΕΤa CD40 Ang II Ενεργό ROS NF-κB AT 1
ET-1 AT Αλδοστερόνη PAI-1 1 vWF TPA Ang II
CRP
Αθηρωματική Ενδοθήλιο πλάκα
Λείες μυικές ίνες
Αφθώδη κύτταρα Αng II Μακροφάγα EGFR IGFR AT Πρωτεΐνες 1 PDGFR στρώματος ΝΑD(P)H c-SRC c-SRC Ερυθροκύτταρα οξειδάση Ang II Αιμοπετάλια ROS Protein tyrosine PLCI phosphatases 1 Λιπίδια AT PLD PKC 2 AA MAPK Src, Ras PLA JAK/STAT, PI3K ETa I-κΒ Αλδοστερόνη ET Ανενεργός NF-κΒ TNFα Ενεργός IL-6 NF-κΒ MCP-1 VCAM-1 ICAM-1
™¯. 1. ªÔÚÈ·ÎÔ› Ì˯·ÓÈÛÌÔ› ·ÁÁÂȷ΋˜ ÊÏÂÁÌÔÓ‹˜.
ÚˆÓ22. ∂ÈÚfiÛıÂÙ·, Ë ·ÁÁÂÈÔÙÂÓÛ›ÓË ππ ‰ÈÂÁ›ÚÂÈ ÙËÓ Ù·Ú·, ÛÙ· Ï›· Ì˘˚ο ·ÙÙ·Ú·, ÛÙÔ˘˜ ÈÓÔ‚Ï¿ÛÙ˜ Î·È ·Ú·ÁˆÁ‹ ÙÔ˘ ƒ∞π-1 Ô˘ Û˘Ì‚¿ÏÏÂÈ ÙfiÛÔ ÛÙË ‰ËÌÈ- ÛÙ· ÌÔÓÔ·ÙÙ·Ú·/Ì·ÎÚÔÊ¿Á·. ∏ ·ÁÁÂÈÔÙÂÓÛ›ÓË ππ Î·È Ô˘ÚÁ›· ÚÔ-ıÚÔÌ‚ˆÙÈ΋˜ ‰È¿ıÂÛ˘ fiÛÔ Î·È ÛÙË Ú‹- Ë ÂÓ‰ÔıËÏ›ÓË-1, Ù˘ ÔÔ›·˜ Ë ·Ú·ÁˆÁ‹ ‰ÈÂÁ›ÚÂÙ·È ÍË Ù˘ ·ıËڈ̷ÙÈ΋˜ Ͽη˜23. ∂ÈϤÔÓ, ‰ÈÂÁ›ÚÂÈ ·fi ÙËÓ ÚÒÙË, ÙÚÔÔÔÈÔ‡Ó ÙË ‚·ÛÈ΋ ·Ú·ÁˆÁ‹ 26 ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ ÌÂÙ·ÏÏÔÚˆÙ·ÛÒÓ Ù˘ ıÂ̤- ˘ÂÚÔÍÂȉ›ˆÓ . ÏÈ·˜ Ô˘Û›·˜, Ô˘ ÚÔηÏÔ‡Ó ÙËÓ ·Ô‰fiÌËÛË ÙÔ˘ ÈÓÒ‰Ô˘˜ ¯ÈÙÒÓ· Ù˘ Ͽη˜ Û˘Ì‚¿ÏÏÔÓÙ·˜ ÛÙË Ú‹ÍË C-∞ÓÙȉÚÒÛ· ÚˆÙ½ÓË: ‰Â›ÎÙ˘ ‹ ÌÂ- Ù˘24. √È ÂÓÂÚÁ›˜ Ú›˙˜ Ô͢ÁfiÓÔ˘ (ROS) ‰ÚÔ˘Ó ˆ˜ ÛÔÏ·‚ËÙ‹˜ Ù˘ ÊÏÂÁÌÔÓ‹˜ ÛÙËÓ ˘¤Ú- ÛËÌ·ÙÔ‰ÔÙÈο ÌfiÚÈ· ÙÚÔÔÔÈÒÓÙ·˜ ÙÔÓ ·ÁÁÂÈ·Îfi Ù·ÛË Î·È ÙËÓ Î·Ú‰È·ÁÁÂȷ΋ ÓfiÛÔ; ÙfiÓÔ, ÚÔηÏÒÓÙ·˜ ÌÂÙ·‚ÔϤ˜ ÛÙË ÌÈÎÚÔ΢ÎÏÔÊÔÚ›· ∏ CRP, ÚˆÙ½ÓË ÔÍ›·˜ Ê¿Û˘, ÂÎÊÚ¿˙ÂÙ·È Û¯Â‰fiÓ Î·È ÂÈÙ·¯‡ÓÔÓÙ·˜ ÙËÓ ÂͤÏÈÍË Ù˘ ·ÚÙËÚÈÔÛÎÏ‹Úˆ- ·ÔÎÏÂÈÛÙÈο ÛÙ· Ë·ÙÔ·ÙÙ·Ú· ˆ˜ ̤ÚÔ˜ Ù˘ ·¿- Û˘25. ∏ NAD(P)H ÔÍÂȉ¿ÛË Â›Ó·È Ë ÛËÌ·ÓÙÈÎfiÙÂÚË ÓÙËÛ˘ Û ÈÛÙÈ΋ ‚Ï¿‚Ë, Ïԛ̈ÍË, ÊÏÂÁÌÔÓ‹ Î·È Î·- ËÁ‹ ÙˆÓ ROS Î·È ÂÎÊÚ¿˙ÂÙ·È ÛÙ· ÂÓ‰ÔıËÏȷο ·Ù- ÎÔ‹ıÂȘ ÓÂÔϷۛ˜27. ∞fi ÔÏ˘¿ÚÈı̘ ÂȉËÌÈÔÏÔ- 60 ∞ÁÁÂȷ΋ ÊÏÂÁÌÔÓ‹ ÛÙËÓ ˘¤ÚÙ·ÛË Î·È ÙÔÓ Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË
Προφλεγμονώδεις παράγοντες κινδύνου
Πρωτογενείς προφλεγμονώδεις κυτταροκίνες (eg, IL-1, TNF-α)
IL-6 ICAM-1 «Αγγελιοφόρος» κυτταροκίνη Selectins, HSPs, etc. CRP SAA Ενδοθήλιο και Liver λοιπά κύτταρα
Κυκλοφορία
™¯. 2. ∏ ‰È·‰Èηۛ· Ù˘ ÊÏÂÁÌÔÓ‹˜ ÙˆÓ ·ÁÁ›ˆÓ Î·È ÔÈ Èı·ÓÔ› ˘Ô„‹ÊÈÔÈ ‰Â›ÎÙ˜ ÁÈ· ÚÔÛ‰ÈÔÚÈÛÌfi ÛÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË.
ÁÈΤ˜ ÌÂϤÙ˜ ¤¯ÂÈ ‰Âȯı› fiÙÈ Ù· ·˘ÍË̤ӷ ›‰¿ Ù˘ ٷ͇ ÙˆÓ ÔÔ›ˆÓ Ë ˘¤ÚÙ·ÛË Î·È Ô Û·Î¯·Ú҉˘ ‰È·- ÛÙÔ Ï¿ÛÌ· ÚÔ‰Èο˙Ô˘Ó Ì ·ÎÚ›‚ÂÈ· ÈÛ¯·ÈÌÈο ηÚ- ‚‹Ù˘, ÔÈ ÔÔ›ÔÈ ÂÓÂÚÁÔÔÈÔ‡Ó ‰È·‰Èηۛ˜ ÊÏÂÁÌÔ- ‰È·ÁÁÂȷο ÂÂÈÛfi‰È· (·ÁÁÂÈ·Îfi ÂÁÎÂÊ·ÏÈÎfi ÂÂÈÛfi‰ÈÔ, Ó‹˜. ∂Ô̤ӈ˜, ·fi ·ıÔÊ˘ÛÈÔÏÔÁÈ΋˜ ÛÎÔÈ¿˜, ˘- ÂÚÈÊÂÚÈ΋ ·ÁÁÂȷ΋ ÓfiÛÔ, ·ÈÊÓ›‰ÈÔ Î·Ú‰È·Îfi ı¿Ó·ÙÔ ¿Ú¯Ô˘Ó ÔÏÏÔ› ˘Ô„‹ÊÈÔÈ ‰Â›ÎÙ˜-ÛÙfi¯ÔÈ ÁÈ· ÚÔÛ- Î·È ¤ÌÊÚ·ÁÌ· ÙÔ˘ Ì˘Ôηډ›Ô˘) Û ·ÛıÂÓ›˜ Ì ÛÙ·- ‰ÈÔÚÈÛÌfi ÛÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË, Ì ÙËÓ ¤ÓÓÔÈ· ›Ù Ù˘ ıÂÚ‹ ‹ ·ÛÙ·ı‹ ÛÙËı¿Á¯Ë, ·ÏÏ¿ ·ÎfiÌË Î·È ÌÂٷ͇ ‰È¿ÁÓˆÛ˘ ›Ù Ù˘ ÚfiÁÓˆÛ˘ Ù˘ ÂͤÏÈ͢ Ù˘ ˘ÁÈÒÓ ·ÙfïÓ. ∞˘ÍË̤ӷ ›‰¿ Ù˘ Û˘Û¯ÂÙ›˙ÔÓÙ·È ÊÏÂÁÌÔÓÒ‰Ô˘˜ ‰È·‰Èηۛ·˜. ªÂٷ͇ ·˘ÙÒÓ ÂÚÈÏ·Ì- Ì ϤÔÓ Â‡ıÚ·˘ÛÙ˜ ·ıËڈ̷ÙÈΤ˜ ϿΘ28,29. ∂›- ‚¿ÓÔÓÙ·È ÔÈ ÚÔ-ÊÏÂÁÌÔÓÒ‰ÂȘ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ Û˘, ¤¯ÂÈ ‰È·ÈÛÙˆı› ıÂÙÈ΋ Û˘Û¯¤ÙÈÛË ÌÂٷ͇ Ù˘ fiˆ˜ Ë ÔÍÂȉˆÌ¤ÓË-LDL ¯ÔÏËÛÙÂÚ›ÓË, ÔÈ ÚÔ-ÊÏÂÁ- CRP Î·È ·ÚÙËÚȷ΋˜ ·Î·Ì„›·˜, Û˘ÛÙÔÏÈ΋˜ ·ÚÙËÚÈ·- ÌÔÓÒ‰ÂȘ ΢ÙÙ·ÚÔΛÓ˜ (.¯., ÈÓÙÂÚÏ¢ΛÓË-1, ·Ú¿- ΋˜ ›ÂÛ˘, ·̷ÙÔ˜ ÛÊ˘ÁÌÔ‡ Î·È ˘¤ÚÙ·Û˘30. ÁˆÓ Ó¤ÎÚˆÛ˘ fiÁÎÔ˘), ÌfiÚÈ· ÚÔÛÎfiÏÏËÛ˘ (ICAM- ∏ ·ÎÚÈ‚‹˜ ·ıÔÊ˘ÛÈÔÏÔÁÈ΋ Ù˘ ÛËÌ·Û›· ‰ÂÓ 1, ÛÂÏÂÎÙ›Ó˜), ÊÏÂÁÌÔÓÒ‰Ë ÂÚÂı›ÛÌ·Ù· Ì ˷ÙÈ΋ ¤¯ÂÈ Á›ÓÂÈ Ï‹Úˆ˜ ηٷÓÔËÙ‹ Î·È ·ÔÙÂÏ› ·ÓÙÈΛÌÂÓÔ ‰Ú¿ÛË (ÈÓÙÂÚÏ¢ΛÓË-6) ‹ ÚÔ˚fiÓÙ· Ë·ÙÈ΋˜ ‰È¤ÁÂÚ- ·ÓÙÈ·Ú¿ıÂÛ˘ ηٿ fiÛÔ Â›Ó·È ¤Ó·˜ ·Ú¿ÁÔÓÙ·˜ Û˘ (SAA, CRP ‹ ¿ÏϘ ÚˆÙ½Ó˜ ÔÍ›·˜ Ê¿Û˘)33- ÎÈÓ‰‡ÓÔ˘ ‹ ·ÏÒ˜ ¤Ó·˜ ÌÂÛÔÏ·‚ËÙ‹˜ Ù˘ ·ÁÁÂȷ΋˜ 35. £· Ú¤ÂÈ Ó· ÙÔÓÈÛı› fiÙÈ Â›Ó·È Èı·Ófi ÔÈ ‰Â›ÎÙ˜ ÓfiÛÔ˘. À¿Ú¯Ô˘Ó ÂӉ›ÍÂȘ ÂÓ·fiıÂÛ‹˜ Ù˘ ÛÙËÓ ·˘ÙÔ› Ó· Â›Ó·È ·˘ÍË̤ÓÔÈ ·fi ¿ÏÏË ·ÁÁÂȷ΋ ‚Ï¿‚Ë, ·ıËڈ̷ÙÈ΋ Ͽη Î·È Ê·›ÓÂÙ·È Ó· Û˘Ì‚¿ÏÏÂÈ ÛÙÔÓ ÂÎÙfi˜ ·fi ÙËÓ ·ıËڈ̷ÙÈ΋, ‹ Ó· ÔÊ›ÏÂÙ·È Ë ·‡ÍË- Û¯ËÌ·ÙÈÛÌfi ÙˆÓ ·ÊÚˆ‰ÒÓ Î˘ÙÙ¿ÚˆÓ. ∂›Û˘, ÚÔ¿- Û‹ ÙÔ˘˜ ÛÂ Û˘ÛÙËÌ·ÙÈΤ˜ ÊÏÂÁÌÔÓ¤˜ (ÓÔÛ‹Ì·Ù· ÙÔ˘ ÁÂÈ ÙË ¯ËÌÂÈÔÙ·Í›· ÙˆÓ ÌÔÓÔ΢ÙÙ¿ÚˆÓ Î·È ÙËÓ Úfi- Û˘Ó‰ÂÙÈÎÔ‡ ÈÛÙÔ‡) ‹ ÂÛÙȷΤ˜ ÏÔÈÌÒÍÂȘ (.¯., Ô˘Ï›ÙÈ- ÛÏË„Ë Ù˘ ÔÍÂȉˆÌ¤Ó˘ LDL ·fi Ù· Ì·ÎÚÔÊ¿Á·31,32. ‰·, ÚÔÛÙ·Ù›Ùȉ·, ‚ÚÔÁ¯›Ùȉ·, Ô˘ÚÔÏÔÈÌÒÍÂȘ ‹ Á·- ŸÏ· Ù· ·Ú·¿Óˆ Û˘ÓËÁÔÚÔ‡Ó fiÙÈ Â›Ó·È Î¿ÙÈ ÂÚÈÛ- ÛÙÚÈΤ˜ ÏÔÈÌÒÍÂȘ)36. ÛfiÙÂÚÔ ·fi ¤Ó·˜ ·Ïfi˜ ‰Â›ÎÙ˘ ÊÏÂÁÌÔÓ‹˜. ¶·ÚfiÏ· ∂ÓÙÔ‡ÙÔȘ, ÔÈ ‰Â›ÎÙ˜, Ô˘ ÚԷӷʤÚıËηÓ, ÁÈ· ·˘Ù¿ Ô ÚfiÏÔ˜ Ù˘ ˆ˜ ÙÚÔÔÔÈËÙ‹˜ Ù˘ ÊÏÂÁÌÔÓ‹˜ Ó· Â›Ó·È ¯Ú‹ÛÈÌÔÈ ÛÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË Ú¤ÂÈ Ó· Î·È Ù˘ ıÚfiÌ‚ˆÛ˘ ·Ú·Ì¤ÓÂÈ ·ÓÂÍȯӛ·ÛÙÔ˜. ¤¯Ô˘Ó Î·È ÔÚÈṲ̂ӷ ÂÈÚfiÛıÂÙ· ¯·Ú·ÎÙËÚÈÛÙÈο37. ªÂٷ͇ ·˘ÙÒÓ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È: 1) Ë ÈηÓfiÙËÙ· ÛÙ·- ¢Â›ÎÙ˜ ÊÏÂÁÌÔÓ‹˜ Î·È Î·Ú‰È·ÁÁÂÈ·- ıÂÚÔÔ›ËÛ˘ Ù˘ ÌÂıfi‰Ô˘, 2) Ë ·ÓÂÍ·ÚÙËÛ›· ·fi ΋ ÓfiÛÔ˜ ηıÈÂڈ̤ÓÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘, 3) Ë Û˘Ó‡·Ú- ÍË Ì ηډȷÁÁÂȷο ηٷÏËÎÙÈο ÛËÌ›· Û ÌÂϤÙ˜ ∂Ê·ÚÌÔÁ‹ ÙÔ˘˜ ÛÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË ·Ú·Ù‹ÚËÛ˘ Î·È ÎÏÈÓÈΤ˜ ‰ÔÎÈ̤˜, 4) Ë ‡·ÚÍË Ê˘- Ÿˆ˜ ¤¯ÂÈ ‹‰Ë ·Ó·ÊÂÚı›, Ë Î·Ú‰È·ÁÁÂȷ΋ ÓfiÛÔ˜ ÛÈÔÏÔÁÈÎÒÓ ÙÈÌÒÓ ÁÈ· ÙËÓ ÂÚÌËÓ›· ÙˆÓ ·ÔÙÂÏÂÛÌ¿- ÚÔηÏÂ›Ù·È ·fi ÁÓˆÛÙÔ‡˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘, ÌÂ- ÙˆÓ, 5) Ë ÈηÓfiÙËÙ· Ó· ‚ÂÏÙÈÒÓÔ˘Ó ÙË Û˘ÓÔÏÈ΋ Úfi- ∫. ¶·Ï¤Ù·˜ 61
ÁÓˆÛË ¤Ú·Ó ÙˆÓ ·Ú·‰ÔÛÈ·ÎÒÓ ·Ú·ÁfiÓÙˆÓ ÎÈÓ‰‡- 8. Bakker EN, et al. Inward remodeling follows chronic vaso- ÓÔ˘, 6) Ë ÁÂӛ΢ÛË ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ Û ‰È¿ÊÔÚ˜ constriction in isolated resistance arteries. J Vasc Res, 2002; 39(1): 12-20. ÏËı˘ÛÌȷΤ˜ ÔÌ¿‰Â˜, 7) ÙÔ ·Ô‰ÂÎÙfi ÎfiÛÙÔ˜. ΔÔ 9. O’Rourke MF, et al. Clinical applications of arterial stiffness; ÚÒÙÔ ÂÚÒÙËÌ· Ô˘ Û˘Ó‹ıˆ˜ Ù›ıÂÙ·È Ì ÙÔ˘˜ ‰È¿- definitions and reference values. Am J Hypertens, 2002; ÊÔÚÔ˘˜ ‰Â›ÎÙ˜ Â›Ó·È Î·Ù¿ fiÛÔ Â›Ó·È ¤Ó·˜ ·Ú¿ÁÔ- 15(5): 426-44. ÓÙ·˜ ÎÈÓ‰‡ÓÔ˘ ‹ ·ÏÒ˜ ‰Â›ÎÙ˘ Ù˘ ÊÏÂÁÌÔÓ‹˜. ªÂ 10. Libby P, Ridker PM, Maseri A. Inflammation and athero- ¿ÏÏ· ÏfiÁÈ·, Â›Ó·È Ë ÚÔÛ‰ÈÔÚÈ˙fiÌÂÓË Ô˘Û›· ¤Ó· ‚‹Ì· sclerosis. Circulation, 2002; 105(9): 1135-43. ÛÙË ‰È·‰Èηۛ· Ù˘ ·ıËÚÔÛÎÏ‹ÚˆÛ˘ ‹ ·Ï¿ Ë Âͤ- 11. Festa A, et al. Chronic subclinical inflammation as part of ÏÈÍË Ù˘ ÓfiÛÔ˘; ŒÓ· ¿ÏÏÔ ÂÚÒÙËÌ· Â›Ó·È ÁÈ· ÔÈ· ·Á- the insulin resistance syndrome: the Insulin Resistance ÁÂȷ΋ ‚Ï¿‚Ë ÂÍÂȉÈ·ÂÙ·È, ÙˆÓ ÛÙÂÊ·ÓÈ·›ˆÓ, ÙˆÓ Atherosclerosis Study (IRAS). Circulation, 2000; 102: 42- 7. ÂÁÎÂÊ·ÏÈÎÒÓ ‹ ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ·ÁÁ›ˆÓ; ΔÔ ÙÚ›ÙÔ 12. Libby P. Current concepts of the pathogenesis of the acute ÂÚÒÙËÌ· Â›Ó·È ·Ó Ô ‰Â›ÎÙ˘ ‰È·Ê¤ÚÂÈ ÛÙË Ì·ÎÚÔ¯Úfi- coronary syndromes. Circulation, 2001; 104(3): 365-72. ÓÈ· ‹ ‚Ú·¯˘¯ÚfiÓÈ· ÚfiÁÓˆÛË. Δ¤ÏÔ˜, ·Ó Ë Ì¤ÙÚËÛË 13. Blake GJ, Ridker PM. Novel clinical markers of vascular wall ÙÔ˘ ‰Â›ÎÙË ‰Â›¯ÓÂÈ ÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Ù˘ ıÂÚ·- inflammation. Circ Res, 2001; 89(9): 763-71. ›·˜ ‹ ÌÂÙ·‚¿ÏÏÂÈ ÙËÓ ÚfiÁÓˆÛË. 14. Nakashima Y, et al. Upregulation of VCAM-1 and ICAM-1 ∞fi ÙËÓ ·Ó¿Ï˘ÛË ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ ·fi ÂÚÁ·ÛÙË- at atherosclerosis-prone sites on the endothelium in the ÚȷΤ˜ Î·È ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ ÚÔ·ÙÂÈ fiÙÈ Ë hs-CRP ApoE-deficient mouse. Arterioscler Thromb Vasc Biol, ·ÔÙÂÏ› ÚÔÁÓˆÛÙÈÎfi ‰Â›ÎÙË Ô˘ ÏËÚÔ› fiÏ· Ù· ·- 1998; 18(5): 842-51. Ú·¿Óˆ ÎÚÈÙ‹ÚÈ·. £· Ú¤ÂÈ Ó· ÚÔÛ‰ÈÔÚ›˙ÂÙ·È Û 15. Ballantyne CM, Entman ML. Soluble adhesion molecules and the search for biomarkers for atherosclerosis. Circu- ÌÂÙ·‚ÔÏÈο ÛÙ·ıÂÚ¿ ¿ÙÔÌ·, ¯ˆÚ›˜ ÂÌÊ·Ó›˜ ÊÏÂÁÌÔ- lation, 2002; 106(7): 766-7. ÓÒ‰ÂȘ ‹ ÏÔÈÌÒ‰ÂȘ ηٷÛÙ¿ÛÂȘ. ¡· ÚÔÛ‰ÈÔÚ›˙ÂÙ·È 16. Pradhan AD, Rifai N, Ridker PM. Soluble intercellular ad- Û ‰‡Ô ‰Â›ÁÌ·Ù·, ÓËÛÙ›·˜ Î·È Ù˘¯·›Ô,, Î·È Ù· ·ÔÙÂ- hesion molecule-1, soluble vascular adhesion molecule- ϤÛÌ·Ù· Ó· ÂÎÊÚ¿˙ÔÓÙ·È Û mg/L. ∂ÊfiÛÔÓ ÍÂÂÚ- 1, and the development of symptomatic peripheral ÓÔ‡Ó Ù· ›‰· ÙˆÓ >10 mg/L, ı· Ú¤ÂÈ Ó· ·Ô- arterial disease in men. Circulation, 2002; 106(7): 820-5. ÎÏÂÈÛıÔ‡Ó ¿ÏϘ ÊÏÂÁÌÔÓ¤˜ ‹ ÏÔÈÌÒÍÂȘ. ªÂ ›‰· 17. Diep QN, et al. Structure, endothelial function, cell growth, <1.0 mg/L Ô ·ÛıÂÓ‹˜ Â›Ó·È ¯·ÌËÏÔ‡ ÎÈÓ‰‡ÓÔ˘, 1.0 and inflammation in blood vessels of angiotensin II-infu- sed rats: role of peroxisome proliferator-activated rece- ¤ˆ˜ 3.0 mg/L ̤ÙÚÈÔ˘ ÎÈÓ‰‡ÓÔ˘ Î·È >3.0 mg/L ˘„Ë- ptor-gamma. Circulation, 2002; 105(19): 2296-302. ÏÔ‡ ÎÈÓ‰‡ÓÔ˘. √È ˘fiÏÔÈÔÈ ÚÔÛ‰ÈÔÚÈÛÌÔ› ¯ÚÂÈ¿˙Ô- 18. Schiffrin EL, Touyz RM. From bedside to bench to bedside: ÓÙ·È ÂÚ·ÈÙ¤Úˆ ·Ô‰Â›ÍÂȘ Ì ÎÏÈÓÈΤ˜ ‰ÔÎÈ̤˜ ÁÈ· Ó· role of renin-angiotensin-aldosterone system in remo- Á›ÓÔ˘Ó ·Ô‰ÂÎÙÔ› ÁÈ· ÎÏÈÓÈ΋ ¯Ú‹ÛË38. deling of resistance arteries in hypertension. Am J Physiol Heart Circ Physiol, 2004; 287(2): H435-46. μÈ‚ÏÈÔÁÚ·Ê›· 19. Schieffer B, et al. Role of NAD(P)H oxidase in angiotensin II-induced JAK/STAT signaling and cytokine induction. 1. Contreras F, et al. Diabetes and hypertension physiopatho- Circ Res, 2000; 87(12): 1195-201. logy and therapeutics. J Hum Hypertens, 2000; 14 (Suppl 20. Hernandez-Presa M, et al. Angiotensin-converting enzyme 1): S26-31. inhibition prevents arterial nuclear factor-kappa B activa- 2. Adler AI, et al. Association of systolic blood pressure with tion, monocyte chemoattractant protein-1 expression, macrovascular and microvascular complications of type 2 and macrophage infiltration in a rabbit model of early diabetes (UKPDS 36): prospective observational study. accelerated atherosclerosis. Circulation, 1997; 95(6): BMJ, 2000; 321(7258): 412-9. 1532-41. 3. Stehouwer D, et al. Increased urinary albumin excretion, 21. Pueyo ME, et al. Angiotensin II stimulates endothelial va- endothelial dysfunction, and chronic low-grade inflam- scular cell adhesion molecule-1 via nuclear factor-kappaB mation in type 2 diabetes: progressive, interrelated, and activation induced by intracellular oxidative stress. Arte- independently associated with risk of death. Diabetes, rioscler Thromb Vasc Biol, 2000; 20(3): 645-51. 2002; 51(4): 1157-65. 22. Touyz RM, Schiffrin EL. Signal transduction mechanisms 4. Tracy R.P. Inflammation in cardiovascular disease: cart, hor- mediating the physiological and pathophysiological acti- se, or both? Circulation, 1998; 97(20): 2000-2. ons of angiotensin II in vascular smooth muscle cells. 5. Bohlen HG. Localization of vascular resistance changes du- Pharmacol Rev, 2000; 52(4): 639-72. ring hypertension. Hypertension, 1986; 8(3): 181-3. 23. Vaughan DE, Lazos SA, Tong K. Angiotensin II regulates 6. Schiffrin EL. Reactivity of small blood vessels in hyperten- the expression of plasminogen activator inhibitor-1 in sion: relation with structural changes. State of the art le- cultured endothelial cells. A potential link between the cture. Hypertension, 1992; 19( Suppl 2): 111-9. renin-angiotensin system and thrombosis. J Clin Invest, 7. Schiffrin EL. Resistance arteries as endpoints in hyperten- 1995; 95(3): 995-1001. sion. Blood Press Suppl, 1997; 2: 24-30. 24. Galis ZS, et al. Increased expression of matrix metallopro- 62 ∞ÁÁÂȷ΋ ÊÏÂÁÌÔÓ‹ ÛÙËÓ ˘¤ÚÙ·ÛË Î·È ÙÔÓ Û·Î¯·ÚÒ‰Ë ‰È·‚‹ÙË
teinases and matrix degrading activity in vulnerable re- 103(9): 1194-7. gions of human atherosclerotic plaques. J Clin Invest, 33. Tracy RP. Hemostatic and inflammatory markers as risk fa- 1994; 94(6): 2493-503. ctors for coronary disease in the elderly. Am J Geriatr 25. Kalinina N, et al. Cytochrome b558-dependent NAD(P)H Cardiol, 2002; 11(2): 93-100, 107. oxidase-phox units in smooth muscle and macrophages 34. Danesh J, et al. Low grade inflammation and coronary he- of atherosclerotic lesions. Arterioscler Thromb Vasc Biol, art disease: prospective study and updated meta-ana- 2002; 22(12): 2037-43. lyses. BMJ, 2000; 321(7255): 199-204. 26. Fukui T, et al. p22phox mRNA expression and NADPH 35. Ridker PM, et al. Comparison of C-reactive protein and oxidase activity are increased in aortas from hyperten- low-density lipoprotein cholesterol levels in the predi- sive rats. Circ Res, 1997; 80(1): 45-51. ction of first cardiovascular events. N Engl J Med, 2002; 27. Pepys MB, Hirschfield GM. C-reactive protein: a critical 347(20): 1557-65. update. J Clin Invest, 2003; 111(12): 1805-12. 36. Sakkinen PA, et al. Analytical and biologic variability in 28. Ridker PM, et al. Inflammation, aspirin, and the risk of car- measures of hemostasis, fibrinolysis, and inflammation: diovascular disease in apparently healthy men. N Engl J assessment and implications for epidemiology. Am J Epi- Med, 1997; 336(14): 973-9. demiol, 1999; 149(3): 261-7. 29. Ridker PM, et al. Prospective study of C-reactive protein 37. Mosca L. C-reactive protein – to screen or not to screen? and the risk of future cardiovascular events among appa- N Engl J Med, 2002; 347(20): 1615-7. rently healthy women. Circulation, 1998; 98(8): 731-3. 38. Pearson TA, et al. Markers of inflammation and cardio- 30. Chae CU, et al. Blood pressure and inflammation in appa- vascular disease: application to clinical and public health rently healthy men. Hypertension, 2001; 38(3): 399-403. practice: A statement for healthcare professionals from 31. Torzewski M, et al. C-reactive protein in the arterial intima: the Centers for Disease Control and Prevention and the role of C-reactive protein receptor-dependent monocy- American Heart Association. Circulation, 2003; 107(3): te recruitment in atherogenesis. Arterioscler Thromb 499-511. Vasc Biol, 2000; 20(9): 2094-9. 32. Zwaka TP, Hombach V, Torzewski J. C-reactive protein- mediated low density lipoprotein uptake by macropha- ∞ÏÏËÏÔÁÚ·Ê›·: ges: implications for atherosclerosis. Circulation, 2001; E-mail: [email protected] ∑. ¶·ÏÏ·ÓÙ˙¿ Î·È Û˘Ó. 69
20. Vogelstein B, Kinzler KW. The multistep nature of cancer. 25. Abu-Shakra M, Shoenfeld Y. Introduction to natural auto- Trends Genet. 1993; 9(4): 138-41. antibodies. In: Shoenfeld Y, Isenberg D, eds. Natural au- 21. Tishler M, Shoenfeld Y. Paraneoplastic syndromes. In: toantibodies. Boca Raton, Florida: CRC Press, 1993; 15- Shoenfeld Y, Fishman P, Gershwin ME, eds. Cancer and 33. autoimmunity. Amsterdam: Elsevier, 2000; 121-33. 26. Fernandez Madrid F, Vande Vord PJ, Yang X, Karvonen RL, 22. Burek GL., Rose NR. Autoantibodies. In. R. B. Collins, H. K. Simpson PM, Kraut MJ, et al. Antinuclear antibodies as Bhan, and R. T. McCluskey (eds.), Diagnostic Immuno- potential markers of lung cancer. Clin Cancer Res. 1999; pathology, 1995; 207-30. 5(6): 1393-400. 23. Torchilin VP, Levchenko TS, Rammohan R, Volodina N, 27. Toubi E , Shoenfield Y. Protective Autoimmunity in cancer Papahadjopoulos-Sternberg B, D’Souza GG. Cell transfe- Onco Rep 2007; 17: 245-51. ction in vitro and in vivo with nontoxic TAT peptide- 28. Shrivastav M, Mittal B, Aggarwal A, Misra R. Autoantibo- liposome-DNA complexes. Proc Natl Acad Sci USA. dies against cytoskeletal proteins in Rheumatoid Arthri- 2003; 100(4): 1972-7. tis. Clin Rheumatol. 2002; 21(6): 505-10. 24. Konstadoulakis MM, Syrigos KN, Albanopoulos C, Mayers G, Golematis B. The presence of anti-CEA antibodies in the sera of patients with gastrointastinal malignancies. J ∞ÏÏËÏÔÁÚ·Ê›·: Clin Immunol. 1994; 14(5): 310-3. E-mail: [email protected] 68 ∞Ó›¯Ó¢ÛË ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Ù˘ Ì˘ÔÛ›Ó˘ Û ·ÛıÂÓ›˜ Ì ηÚΛÓÔ ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘
‰· ÙÔ˘ IgG ÎÏ¿ÛÌ·ÙÔ˜ ¤Ó·ÓÙÈ Ù˘ Ì˘ÔÛ›Ó˘ Ô˘ 129-34. ·Ú·ÙËÚ‹ıËÎ·Ó ÛÙÔ˘˜ ›‰ÈÔ˘˜ ·ÛıÂÓ›˜. ∏ ÚÔËÁÔ‡- 2. Kitchen BJ, Boxer LA. Large granular lymphocyte leukemia ÌÂÓË Â˘·ÈÛıËÙÔÔ›ËÛË ÙÔ˘ ·ÓÔÛÈ·ÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ (LGL) in a child with hyper IgM syndrome and autoim- mune hemolytic anemia. Pediatr Blood Cancer. 2008; ÛÙ· ·˘ÙÔ·ÓÙÈÁfiÓ· Ê·›ÓÂÙ·È Ó· Ô‰ËÁ› ÛÙË ‰ËÌÈÔ˘ÚÁ›· 50(1): 142-5. ΢ÙÙ¿ÚˆÓ ÌÓ‹Ì˘ Ù· ÔÔ›· ÌÂÙ¿ ÙËÓ Â¤Ì‚·ÛË ÂÓÂÚ- 3. Gordon PA., Baylis PH., Bird GW. Tumor induced autoi- ÁÔÔÈÔ‡ÓÙ·È Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ Â·ÁˆÁ‹ ÙÔ˘ πgG mmune haemolytic anemia. Br Med J. 1976; 1(6025): ÎÏ¿ÛÌ·ÙÔ˜. Δ· ¯·ÌËÏ¿ ›‰· ÙÔ˘ IgM ÎÏ¿ÛÌ·ÙÔ˜ 1569-70. ¤Ó·ÓÙÈ Ù˘ Ì˘ÔÛ›Ó˘ ‰ÂÓ ¤¯Ô˘Ó ÌÂÏÂÙËı› ‰ÈÂÍÔ‰Èο 4. Cho-Chung YS. Autoantibody biomarkers in the detection ÛÙË ‚È‚ÏÈÔÁÚ·Ê›·. ∞˘ÙÔ·ÓÙÈÛÒÌ·Ù· ·˘Ù‹˜ Ù˘ ÎÏ¿- of cancer. Biochim Biophys Acta. 2006; 1762(6): 587-91. Û˘ ¤Ó·ÓÙÈ ¿ÏÏˆÓ ·ÓÙÈÁfiÓˆÓ ¤¯Ô˘Ó ‚ÚÂı› ·˘ÍË̤ӷ 5. Admon A, Shoshan SH. Antibodies as oncogenes: A hy- Û ·ÛıÂÓ›˜ Ì ηÚΛÓÔ27. pothesis. Med Hypotheses. 2006; 67(3): 471-3. ¶·ÚfiÙÈ Ô ·ÚÈıÌfi˜ ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ·ÚÔ˘ÛÈ¿- 6. Houghton AN. Cancer antigens: immune recognition of self and altered self. J Exp Med. 1994; 180(1):1-4. ˙ÔÓÙ·È ÛÙË ÌÂϤÙË ·˘Ù‹ Â›Ó·È ÂÚÈÔÚÈṲ̂ÓÔ˜, Ë Â- 7. de Fromentel C.C., May-Levin F., Mouriesse H et al. Pre- ÓÙ·ÂÙ‹˜ ÙÔ˘˜ ·Ú·ÎÔÏÔ‡ıËÛË ¤‰ˆÛ ÙË ‰˘Ó·ÙfiÙËÙ· sence of circulating antibodies against cellular protein Ó· ÂÎÙÈÌËı› Ë ÛËÌ·Û›· Ù˘ ·Ú·ÁˆÁ‹˜ ÙˆÓ ·˘ÙÔ·- p53 in a notable proportion of children with B-cell lym- ÓÙÈۈ̿وÓ. ∏ ·ÚÔ˘Û›· IgG ·ÓÙÈÛˆÌ¿ÙˆÓ Ì˘ÔÛ›Ó˘ phoma. Int J Cancer. 1987; 39(2): 185-9. Û ·ÛıÂÓ›˜ Ì ÔÚıÔÎÔÏÈÎfi ηÚΛÓÔ, Ë ÔÔ›· Û˘Ó‰¤- 8. Winter SF., Minna JD., Johnson BE., Takahashi T. et al. Deve- ÂÙ·È Ì ¢ÓÔ˚΋ ÚfiÁÓˆÛË, ·Ó·Ê¤ÚÂÙ·È ÁÈ· ÚÒÙË lopment of antibodies against p53 in lung cancer patients ÊÔÚ¿. £· Ú¤ÂÈ Ó· Á›ÓÔ˘Ó Û˘ÌÏËڈ̷ÙÈΤ˜ ÌÂϤ- appears to be dependent on the type of p53 mutation, Cancer Res. 1992; 52(15): 4168-74. Ù˜ Ì ÌÂÁ·Ï‡ÙÂÚÔ ·ÚÈıÌfi ·ÛıÂÓÒÓ ÒÛÙ ӷ ηıÔÚÈ- 9. Disis ML, Pupa SM, Gralow JR, et al. Existent T-cell and an- ÛÙ› Â¿Ó Ù· ·˘ÙÔ·ÓÙÈÛÒÌ·Ù· Ì˘ÔÛ›Ó˘ ¤¯Ô˘Ó ‰È·ÁÓˆ- tibody immunity to HER-2/neu protein in patients with ÛÙÈ΋ Î·È ÚÔÁÓˆÛÙÈ΋ ÛËÌ·Û›·. breast cancer. Cancer Res. 1994; 54(1): 16-20. 10. Takahashi M, Chen W, Byrd DR, et al. Antibody to ras Abstract proteins in patients with colon cancer. Clin Cancer Res. 1995; 1(10): 1071-7. Pallantza ∑, Nikolopoulou ª, Memos ¡, Kataki ∞, Ka- 11. Covini G, Chan EK, Nishioka M, et al. Immune response to rantzikos G, Alexandropoulos N, Panetsos G, Konsta- cyclin B1 in hepatocellular carcinoma. Hepatology. 1997; doulakis MM. Autoimmune response against myosin in 25(1): 75-80. colorectal cancer patients. Anosia 2009; 1: 63-69. 12. Titu LV, Monson JR, Greenman J. The role of CD8(+) T cells in immune responses to colorectal cancer. Cancer Correlation of neoplastic disease with autoimmunity has dire- Immunol Immunother. 2002; 51(5): 235-47. cted research towards the study of variety of autoantibodies in 13. Topping KP, Hough VC, Monson JR, Greenman J. Isolation cancer patients without any obvious autoimmune disease. In the of human colorectal tumour reactive antibodies using pha- ge display technology. Int J Oncol. 2000; 16(1): 187-95. present study, free circulating antibodies against myosin were 14. Neu N, Beisel KW, Traystman MD, et al. Autoantibodies measured with enzyme linked immunoassay (ELISA) in 22 he- specific for the cardiac myosin isoform are found in mice althy subjects and in 20 colorectal cancer patients, prior and one susceptible to coxsackie virus B3-induced myocarditis. J month after surgery and correlated with the clinical outcome of Immunol. 1987; 138(8): 2488-92. the disease. While a significant reduction in the mean level of 15. Leibovitch L, George J, Levi Y, et al. Antiactin autoantibo- anti-myosin IgM was observed after surgical resection compared dies in sera from patients with autoimmune liver diseases to controls and before (p=0.002 and p=0.001 respectively), the and patients with carcinoma by ELISA. Immunol Lett. mean levels of autoantibodies against anti-myosin IgG were 1995; 48(2): 129-32. significantly increased in both pre- and post-surgical specimens 16. Syrigos KN, Charalambopoulos A, Pliarchopoulou K, et al. compared to controls (p=0.027 and p=0.007 respectively). Cox The prognostic significance of autoantibodies against regression analysis revealed favourable prognosis in patients dsDNA in patients’ with colorectal adenocarcinoma. An- ticancer Res. 2000; 20(6B): 4351-3. with increased levels of anti-myosin IgG antibodies. These natu- rally occurring events in the immune system might reflect the in- 17. Blaes F, Klotz M, Huwer H, et al. Antineural and antinuclear autoantibodies are of prognostic relevance in nonsmall duction of antibody response towards tumor specific antigens. cell lung cancer. Ann. Thorac. Surg. 2000; 69(1): 254-8. Key-words: Autoantibodies, ELISA, Myosin, colorectal cancer. 18. Astler VB, Coller FA. The prognostic significance of direct extension of carcinoma of the colon and rectum. Ann μÈ‚ÏÈÔÁÚ·Ê›· Surg. 1954; 139(6): 846-52. 19. Jass JR, Sobin LH. Histological Classification of Tumors: 1. Bernatsky S, Ramsey-Goldman R, Clarke A. Malignancy and Histological Typing of Intestinal Tumors 2nd edition. autoimmunity. Curr Opin Rheumatol. 2006 r; 18(2): New York: World Health Organization International. ∑. ¶·ÏÏ·ÓÙ˙¿ Î·È Û˘Ó. 67
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™¯. 3. ∏ η̇ÏË ÂÈ‚›ˆÛ˘ ηٿ Kaplan-Meier ÙˆÓ 20 ·ÛıÂÓÒÓ Ì ηÚΛÓÔ ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘-ÔÚıÔ‡.
ÂÌÊ¿ÓÈÛË Û¯ÂÙÈÎÒÓ ·Ú·ÓÂÔÏ·ÛÙÈÎÒÓ Û˘Ó‰ÚfiÌˆÓ ·ÊÔ‡ Ù· ›‰· ·Ú¤ÌÂÈÓ·Ó ˘„ËÏ¿ ¤Ó·Ó Ì‹Ó· ÌÂÙ¿ Û ÔÛÔÛÙfi ÂÚ›Ô˘ 7-10%. ∏ ÂÌÊ¿ÓÈÛË ·˘ÙÔ·ÓÙÈ- ÙÔ ¯ÂÈÚÔ˘ÚÁ›Ô. À„ËÏ¿ ›‰· ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ÛˆÌ¿ÙˆÓ ÌÔÚ› Ó· ıˆÚËı› ˆ˜ ·ÔÙ¤ÏÂÛÌ· ‰È¤- Ù‡Ô˘ IgG ¤¯Ô˘Ó ·Ú·ÙËÚËı› Û ·ÛıÂÓ›˜ Ì η- ÁÂÚÛ˘ ÙÔ˘ ·ÓÔÛÈ·ÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ ÏfiÁˆ ÔÚÌÔÓÈÎÒÓ ÎÔ‹ıÂȘ ÙÔ˘ ·ÈÌÔÔÈËÙÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ Î·È Ì ηÚ- ·ÏÏ·ÁÒÓ ‹ ÏfiÁˆ Ù˘ ·Ú·ÁˆÁ‹˜ ‰È·ÊfiÚˆÓ ÂÙȉ›ˆÓ ΛÓÔ ÙÔ˘ Ó‡ÌÔÓ·24,25. ∂ȉÈÎfiÙÂÚ· ÛÙÔÓ Î·ÚΛÓÔ ÙÔ˘ ·fi Ù· ·ÙÙ·Ú· ÙÔ˘ fiÁÎÔ˘20. √È ·ÏÏ·Á¤˜ ·˘Ù¤˜ Â›Ó·È Ó‡ÌÔÓ· Ë ·Ú·ÁˆÁ‹ ·ÓÙÈ-˘ÚËÓÈÎÒÓ ·ÓÙÈÛˆÌ¿ÙˆÓ Èı·Ófi Ó· ÌÔÚÔ‡Ó Ó· ÂÓÙÔÈÛÙÔ‡Ó Î·È Ô ÚfiÏÔ˜ ÙÔ˘˜ IgG ¤¯ÂÈ ıˆÚËı› Èı·Ófi˜ ‰Â›ÎÙ˘ ÁÈ· ÙË ‰È¿ÁÓˆÛË Ó· ÂÎÙÈÌËı› Ì ÙË ‚Ô‹ıÂÈ· ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ Î·È ÚfiÁÓˆÛË ÙˆÓ ·ÛıÂÓÒÓ26. ∏ ‰È·Ù‹ÚËÛË ÙˆÓ ·˘- Ô˘ ÂÌÊ·Ó›˙ÔÓÙ·È Î·Ù¿ ÙËÓ ÔÁÎÔÁ¤ÓÂÛË. ÍËÌ¤ÓˆÓ ÂȤ‰ˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÛÙË Ì˘ÔÛ›ÓË ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË, ÔÚfi˜ ·›Ì·ÙÔ˜ ·fi ·ÛıÂ- Ù‡Ô˘ IgG Û ·ÛıÂÓ›˜ Ì ÔÚıÔÎÔÏÈÎfi ηÚΛÓÔ ÚÈÓ Ó›˜ Ì ηÚΛÓÔ ÙÔ˘ ÔÚıÔÎÔÏÈÎÔ‡ ηÚΛÓÔ˘ ÂϤÁ¯ıË- Î·È ¤Ó·Ó Ì‹Ó· ÌÂÙ¿ ÙÔ ¯ÂÈÚÔ˘ÚÁÂ›Ô ˘Ô‰ËÏÒÓÂÈ fiÙÈ Î ÁÈ· ÙËÓ ·ÚÔ˘Û›· ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ÁÈ· ÙËÓ Î˘ÙÔ- ˘¿Ú¯ÂÈ ÂȉÈ΋ ·˘ÙÔ¿ÓÔÛË ·fiÎÚÈÛË ÛÙË Ì˘ÔÛ›ÓË. ÛÎÂÏÂÙÈ΋ ÚˆÙ½ÓË Ì˘ÔÛ›ÓË ÚÈÓ Î·È ¤Ó·Ó Ì‹Ó· ÌÂÙ¿ ∂ÈϤÔÓ Ù· ·˘ÍË̤ӷ ›‰· ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ÙÔ ¯ÂÈÚÔ˘ÚÁÂ›Ô Î·È Ù· ›‰· Û˘ÁÎÚ›ıËÎ·Ó Ì ·˘Ù¿ ÛÙÔ ·›Ì· Û¯ÂÙ›ÛÙËÎ·Ó Ì ηχÙÂÚË ÚfiÁÓˆÛË, ÁÂ- ·fi ˘ÁÈ›˜ ÂıÂÏÔÓÙ¤˜ ·ÈÌÔ‰fiÙ˜. π‰È·›ÙÂÚË ÚÔÛÔ¯‹ ÁÔÓfi˜ Ô˘ Û˘ÌʈÓ› Ì ÙËÓ ˘¿Ú¯Ô˘Û· ‚È‚ÏÈÔÁÚ·- ‰fiıËΠÒÛÙ ÔÈ ·ÛıÂÓ›˜ Î·È Ë ÔÌ¿‰· ÂϤÁ¯Ô˘ Ó· Ê›· fiÔ˘ Ë ·ÚÔ˘Û›· ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ fiˆ˜ ÙÔ˘ ·ÔÙÂÏÂ›Ù·È ·fi ¿ÙÔÌ· ¯ˆÚ›˜ ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ dsDNA Î·È ÙÔ˘ FAS Û¯ÂÙ›˙ÂÙ·È Ì ηχÙÂÚË Úfi- ‰È·ÊÔÚ¿ ËÏÈΛ·˜, ηıÒ˜ ÛÙÔȯ›· ÚÔËÁÔ‡ÌÂÓˆÓ ÌÂ- ÁÓˆÛË27. ÏÂÙÒÓ ¤‰ÂÈÍ·Ó fiÙÈ Ù· ·˘ÙÔ·ÓÙÈÛÒÌ·Ù· Â›Ó·È ÈÔ ‰È·- ∂›Û˘ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ Û˘ÌÂÚÈÏ‹ÊıËÛ·Ó ‰Â‰Ô̤ӷ Û ÌÂÁ·Ï‡ÙÂÚ˜ ËÏÈ˘21. ª›· Èı·Ó‹ ÂÍ‹- ÛÙËÓ ·ÚÔ‡Û· ÌÂϤÙË ·Ú·ÙËÚ‹ıËΠÛËÌ·ÓÙÈ΋ Ì›- ÁËÛË ÁÈ· ÙËÓ ‡·ÚÍË ·˘ÍËÌ¤ÓˆÓ ÂȤ‰ˆÓ ÌË ÂȉÈÎÒÓ ˆÛË ÛÙÔ Â›Â‰Ô ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÛÙË ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ Û ËÏÈÎȈ̤ӷ ¿ÙÔÌ· Â›Ó·È fiÙÈ ÙÔ Ì˘ÔÛ›ÓË Ù‡Ô˘ IgM, ÁÂÁÔÓfi˜ Ô˘ Û˘ÌʈÓ› Î·È Ì ÙȘ ·ÓÔÛÈ·Îfi ÙÔ˘˜ Û‡ÛÙËÌ· ·ÓÙ·ÔÎÚ›ÓÂÙ·È Û ·ÓÙÈÁfiÓ· ·Ú·ÙËÚ‹ÛÂȘ ¿ÏÏˆÓ ÂÚ¢ÓËÙÒÓ Û¯ÂÙÈο Ì ÙȘ ÙÈ̤˜ Ì ÈÔ ÂÈıÂÙÈÎfi ÙÚfiÔ Û ۯ¤ÛË Ì ·˘Ùfi ÙˆÓ Ó·- IgM. ™‡Ìʈӷ Ì ÙÔÓ Shrivastav M Î·È Û˘Ó. 28, Ë ·ÓÔ- ÚfiÙÂÚˆÓ ·ÙfïÓ22,23. ÛÔÏÔÁÈ΋ ·fiÎÚÈÛË ¤Ó·ÓÙÈ ÛÙÔÓ fiÁÎÔ ÛÙÔ˘˜ ·ÛıÂÓ›˜ ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË ·˘ÍË̤ӷ ›‰· ·˘ÙÔ- ·˘ÙÔ‡˜ ·Ô‰›‰ÂÙ·È Û ‰È¿ÊÔÚ· ΢ÙÙ·ÚÔÛÎÂÏÂÙÈο ·˘- ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Ù˘ Ì˘ÔÛ›Ó˘ Ù‡Ô˘ IgG ÂÓÙÔ›- ÙÔ·ÓÙÈÛÒÌ·Ù· Ô˘ ÂÎÊÚ¿˙ÔÓÙ·È ÛÙÔ ÂÈı‹ÏÈÔ ÙÔ˘ ÛÙËÎ·Ó Û ·ÛıÂÓ›˜ Ì ηÚΛÓÔ ÙÔ˘ ÔÚıÔÎÔÏÈÎÔ‡ ÔÚıÔÎÔÏÈÎÔ‡ ηÚΛÓÔ˘. Δ· ¯·ÌËÏfiÙÂÚ· ›‰· ÙÔ˘ ÚÈÓ ÙÔ ¯ÂÈÚÔ˘ÚÁ›Ô, ÁÂÁÔÓfi˜ Ô˘ ˘Ô‰ÂÈÎÓ‡ÂÈ Â·- πgM ÎÏ¿ÛÌ·ÙÔ˜ Ù˘ Ì˘ÔÛ›Ó˘ ÚÈÓ ÙË ¯ÂÈÚÔ˘ÚÁÈ΋ ÁˆÁ‹ Ù˘ ·˘ÙÔ·ÓÔÛ›·˜. ∏ ·ÁˆÁ‹ ·˘Ù‹ Ê·›ÓÂÙ·È Ó· ¤̂·ÛË Î·È ·ÎfiÌ· ÂÚÈÛÛfiÙÂÚÔ ÌÂÙ¿ ·fi ·˘Ù‹ ‰È·ÙËÚÂ›Ù·È Î·È ÌÂÙ¿ ÙËÓ ·ÔÌ¿ÎÚ˘ÓÛË ÙÔ˘ fiÁÎÔ˘ ÌÔÚÔ‡Ó Èı·Ó¿ Ó· ÂÍËÁËıÔ‡Ó ·fi Ù· ·˘ÍË̤ӷ ›- 66 ∞Ó›¯Ó¢ÛË ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Ù˘ Ì˘ÔÛ›Ó˘ Û ·ÛıÂÓ›˜ Ì ηÚΛÓÔ ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘
¶›Ó·Î·˜ 2. ª¤ÛË ÙÈÌ‹ ÔÙÈ΋˜ ˘ÎÓfiÙËÙ·˜ (± Ù˘ÈÎfi ÛÊ¿ÏÌ·) ÙˆÓ ‰ÂÈÁÌ¿ÙˆÓ ÙÔ˘ ÔÚÔ‡ ÙˆÓ ˘ÁÈÒÓ ÂıÂÏÔÓÙÒÓ, ÙˆÓ ·ÛıÂÓÒÓ Ì ηÚΛÓÔ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘-ÔÚıÔ‡ ÚÈÓ Î·È ÌÂÙ¿ ÙË ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË ÁÈ· ·ÓÙÈÛÒÌ·Ù· Ù‡Ô˘ IgG, IgM, IgA ¤Ó·ÓÙÈ ÛÙË Ì˘ÔÛ›- ÓË.
∞˘ÙÔ·ÓÙÈÛÒÌ·Ù· ÂÓ¿ÓÙÈ· ÀÁÈ›˜ ÂıÂÏÔÓÙ¤˜ ∞ÛıÂÓ›˜ Ì ∞ÛıÂÓ›˜ Ì ÛÙË Ì˘ÔÛ›ÓË Î·ÚΛÓÔ ÙÔ˘ ÂÓÙ¤ÚÔ˘- ηÚΛÓÔ ÙÔ˘ ÂÓÙ¤ÚÔ˘- ÔÚıÔ‡ ÚÈÓ ÙÔ ÔÚıÔ‡ ÌÂÙ¿ ÙÔ ¯ÂÈÚÔ˘ÚÁÂ›Ô ¯ÂÈÚÔ˘ÚÁÂ›Ô IgA 0,06077 0,05115 0,0500 (±,0585) (±,0656) (±,0412) IgG 0,03836 0,07 0,0797 (±,0437) (±,0493) (±,0471) IgM 0,15455 0,0758 0,0451 (±,1408) (±,0595) (±,0323)
0,0800 ** 0,1500
0,0600
0,1000 ** 0,0400 IgΜ μυοσίνη IgG αντι-μυοσίνη
0,0500 0,0200
0,0000 0,0000 Oμάδα ελέγχου Προ χειρουργείου Μετά το χειρουργείο Oμάδα ελέγχου Προ χειρουργείου Μετά το χειρουργείο
™¯. 1. ∂›Â‰· ·˘Ùo·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÛÙË Ì˘ÔÛ›ÓË Û ·ÛıÂ- ™¯. 2. ∂›Â‰· ·˘Ùo·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÛÙË Ì˘ÔÛ›ÓË Û ·ÛıÂ- Ó›˜ Ì ηÚΛÓÔ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘-ÔÚıÔ‡ ÚÈÓ Î·È ÌÂÙ¿ ÙÔ ¯ÂÈ- Ó›˜ Ì ηÚΛÓÔ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘-ÔÚıÔ‡ ÚÈÓ Î·È ÌÂÙ¿ ÙÔ ¯ÂÈ- ÚÔ˘ÚÁÂ›Ô Î·È ÛÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘. ΔfiÛÔ Ù· ›‰· ÚÈÓ ÙË ÚÔ˘ÚÁÂ›Ô Î·È ÛÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘. ∞ÛıÂÓ›˜ Ì ηÚΛÓÔ ·- ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË fiÛÔ Î·È ÌÂÙ¿ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ηÚ- ¯¤Ô˜ ÂÓÙ¤ÚÔ˘-ÔÚıÔ‡ ¤‰ÂÈÍ·Ó ÛÙ·ÙÈÛÙÈÎÒ˜ ÛËÌ·ÓÙÈο ¯·ÌË- ΛÓÔ ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘ Â›Ó·È ·˘ÍË̤ӷ ÛÙ·ÙÈÛÙÈÎÒ˜ ÛËÌ·- ÏfiÙÂÚ· ›‰· ·ÓÙÈÛˆÌ¿ÙˆÓ IgM ÌÂÙ¿ ÙÔ ¯ÂÈÚÔ˘ÚÁÂ›Ô Û ÓÙÈο Û ۯ¤ÛË Ì ÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘. √È ÛًϘ ·ÓÙÈÚÔ- Û¯¤ÛË Ì ÚÈÓ, ÂÓÒ ÙÔ Â›Â‰Ô ÛÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘ Â›Ó·È ÛË- ÛˆÂ‡Ô˘Ó ÙȘ ̤Û˜ ÙÈ̤˜ Ù˘ ÔÙÈ΋˜ ˘ÎÓfiÙËÙ·˜ ÂÓÒ Ù· Ì·ÓÙÈο ˘„ËÏfiÙÂÚÔ. error bars ‰Â›¯ÓÔ˘Ó ÙÔ Ù˘ÈÎfi ÛÊ¿ÏÌ· (S.E.M), *p<0.05.
0,6331 (SE=0.112, ™¯. 3). ∞Ó·Ï˘ÙÈÎfiÙÂÚ·, Ù¤ÛÛÂÚȘ Ó·ÓÙÈ ÛÙË Ì˘ÔÛ›ÓË Ù‡Ô˘ IgG [Exp(B)=0,138 95% CI ·ÛıÂÓ›˜ η٤ÏËÍ·Ó Ì¤Û· Û 24 Ì‹Ó˜, ‰‡Ô ÛÙÔ ¯ÚÔ- – 0,22-0,852 p=0,033] ›¯·Ó ηχÙÂÚË ÂÈ‚›ˆÛË ¤¯Ô- ÓÈÎfi ‰È¿ÛÙËÌ· 24-36 ÌËÓÒÓ Î·È ¤Ó·˜ ÛÙ· 5 ¯ÚfiÓÈ·, ÓÙ·˜ ÂϤÁÍÂÈ ÁÈ· ÙÔ ÛÙ¿‰ÈÔ ˆ˜ ηÙËÁÔÚÈ΋ ÌÂÙ·‚ÏËÙ‹ ÂÓÒ ‰‡Ô ·ÛıÂÓ›˜ ¯¿ıËÎ·Ó Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ Â- Ì ‰‡Ô ›‰· (μ2 ≤ Î·È ≥ C1). ÓÙ·ÂÙÔ‡˜ ·Ú·ÎÔÏÔ‡ıËÛ˘. ∏ Û¯¤ÛË ÙˆÓ ÎÏÈÓÈÎÔ·- ıÔÏÔÁÈÎÒÓ ·Ú·Ì¤ÙÚˆÓ ÙˆÓ ·ÛıÂÓÒÓ Ì ηÚΛÓÔ ÙÔ˘ ™˘˙‹ÙËÛË ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘-ÔÚıÔ‡ Ì ÙËÓ ÂÓÙ·ÂÙ‹ ÂÈ‚›ˆÛË √ ηÚΛÓÔ˜ ÌÔÚ› Ó· ·˘Í‹ÛÂÈ ÙËÓ ÂÌÊ¿ÓÈÛË ·˘ÙÔ¿- ·ÚÔ˘ÛÈ¿˙ÂÙ·È ÛÙÔÓ ›Ó·Î· 1. ¶ÔÏ˘·Ú·ÁÔÓÙÈ΋ ·- ÓÔÛˆÓ Î·È ÚÂ˘Ì·ÙÔÂȉÒÓ ÓÔÛËÌ¿ÙˆÓ. ∞˘ÙÔ¿ÓÔÛË Ó¿Ï˘ÛË Ì ¯Ú‹ÛË ÙÔ˘ ÌÔÓÙ¤ÏÔ˘ ηٿ Cox ¤‰ÂÈÍ fiÙÈ Â·ÁˆÁ‹ Èı·Ófiٷٷ ÚÔηÏ› ·Ú·ÁˆÁ‹ ·˘ÙÔ·ÓÙÈ- ·ÛıÂÓ›˜ Ì ·˘ÍË̤ӷ ›‰· ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤- ÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÙˆÓ Û˘Ó‰¤ÛÌˆÓ Î·È ÙˆÓ Ì˘ÒÓ Î·È ÙËÓ ∑. ¶·ÏÏ·ÓÙ˙¿ Î·È Û˘Ó. 65
¶›Ó·Î·˜ 1. ∫ÏÈÓÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÙˆÓ ·ÛıÂÓÒÓ Ì ηÚΛÓÔ ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘-ÔÚıÔ‡ ηıÒ˜ Î·È Ë ÛËÌ·Û›· ·˘ÙÒÓ ÛÙËÓ Â- ÓÙ·ÂÙ‹ ÂÈ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ.
∞ÚÈıÌfi˜ % 5ÂÙ˘ ÂÈ‚›ˆÛË Rate (%) Log Rank ΔÈÌ‹ p £¤ÛË ¶·¯‡ ¤ÓÙÂÚÔ 7 35 42,86 3,51 0,061 √Úıfi 13 65 76,92 ™Ù·‰ÈÔÔ›ËÛË Î·Ù¿ DUKE A 1 5 100 17,93 0,0005 B 9 45 77,78 C 7 35 71,43 D 3 15 0 πÛÙÔÏÔÁ›· ∞‰ÂÓÔηÚΛӈ̷ 17 85 64,71 0,74 0,39 ∫ÔÏÏÔÂȉ¤˜ 3 15 66,67 ¢È·ÊÔÚÔÔ›ËÛË Ã·ÌËÏ‹ 1 5 0 19,24 0,002 ªÂÛ·›· 11 55 72,73 À„ËÏ‹ 5 25 60 ∫ÔÏÏÔÂȉ¤˜ 3 20 66 ¶·ÚÔ˘Û›· ıÂÙÈÎÒÓ ÏÂÌÊ·‰¤ÓˆÓ ¡·È 12 63,15 66,67 0,41 0,52 Ÿ¯È 7 36,84 57,14 ºÏÂÁÌÔÓ҉˘ ·ÓÙ›‰Ú·ÛË Á‡Úˆ ·fi ÙÔÓ fiÁÎÔ ¡·È 11 57,89 81,82 4,51 0,033 Ÿ¯È 8 42,1 37,50
™Ù·ÙÈÛÙÈ΋ ∞Ó¿Ï˘ÛË Ì˘ÔÛ›ÓË ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È ÛÙÔÓ ›Ó·Î· 2. ™Ù·ÙÈÛÙÈÎÒ˜ ÛËÌ·ÓÙÈο ¯·ÌËÏfiÙÂÚ· ‚Ú¤ıËÎ·Ó √È Ì¤Û˜ ÙÈ̤˜ ÔÙÈ΋˜ ˘ÎÓfiÙËÙ·˜ ± S.E.M, Ô˘ ÂÏ‹- Ù· ›‰· ·ÓÙÈÛˆÌ¿ÙˆÓ Ì˘ÔÛ›Ó˘ Ù‡Ô˘ IgM Û ÌÂ- ÊıËÛ·Ó Ì ÙËÓ Ù¯ÓÈ΋ ELISA, ·Ó·Ï‡ıËÎ·Ó Ì ÙÔ ÛÙ·- ÙÂÁ¯ÂÈÚËÙÈÎÔ‡˜ ·ÛıÂÓ›˜ Ì ÔÚıÔÎÔÏÈÎfi ηÚΛÓÔ Û ÙÈÛÙÈÎfi ·Î¤ÙÔ SPSS 11,5. √ ¤ÏÂÁ¯Ô˜ Mann Whitney Û‡ÁÎÚÈÛË Ì ·˘Ù¿ Ù˘ ÔÌ¿‰·˜ ÂϤÁ¯Ô˘ (p=0,001, ™¯. ¯ÚËÛÈÌÔÔÈ‹ıËΠÁÈ· Ó· ·ÓȯÓ¢ıÔ‡Ó ‰È·ÊÔÚ¤˜ ÛÙ· 1). Δ· ›‰· ÙˆÓ ›‰ÈˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ‹Ù·Ó ÛÙ·- ›‰· ·ÓÙÈÛˆÌ¿ÙˆÓ ÛÙÔÓ ÔÚfi ·Ó¿ÌÂÛ· ÛÙÔ˘˜ ·ÛıÂ- ÙÈÛÙÈÎÒ˜ ÛËÌ·ÓÙÈο ÌÂȈ̤ӷ Î·È Û ۇÁÎÚÈÛË Ì ·˘- Ó›˜ Ì ÔÚıÔÎÔÏÈÎfi ηÚΛÓÔ Î·È ÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘. Ù¿ ÚÈÓ ÙËÓ Â¤Ì‚·ÛË (p=0,002). √È ‰È·ÊÔÚ¤˜ ÛÙ· ›‰· ·ÓÙÈÛˆÌ¿ÙˆÓ ·Ó¿ÌÂÛ· ÛÙ· ∞ÓÙ›ıÂÙ·, ÛÙ·ÙÈÛÙÈÎÒ˜ ÛËÌ·ÓÙÈο ˘„ËÏfiÙÂÚ· ÚÔ-ÂÁ¯ÂÈÚËÙÈο Î·È ÌÂÙÂÁ¯ÂÈÚËÙÈο ‰Â›ÁÌ·Ù· ηÚÎÈÓÔ- ‚Ú¤ıËÎ·Ó Ù· ›‰· ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ·ıÒÓ ÂÎÙÈÌ‹ıËÎ·Ó Ì ‚¿ÛË ÙÔ paired test ηٿ Wilcoxon, ÂÓÒ Ë Èı·ÓfiÙËÙ· ÂÈ‚›ˆÛ˘ ·fi ÙËÓ ·Ûı¤- Ù˘ Ì˘ÔÛ›Ó˘ Ù‡Ô˘ IgG ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ÔÚıÔÎÔ- ÓÂÈ· ÂÎÙÈÌ‹ıËΠ̠ÙË Ì¤ıÔ‰Ô Kaplan-Meier. ªÔÓÔ·- ÏÈÎfi ηÚΛÓÔ ÙfiÛÔ ÚÈÓ fiÛÔ Î·È ÌÂÙ¿ ÙË ¯ÂÈÚÔ˘ÚÁÈ΋ Ú·ÁÔÓÙÈ΋ Î·È ÔÏ˘·Ú·ÁÔÓÙÈ΋ ·Ó¿Ï˘ÛË ÙˆÓ ÌÂÙ·- ¤̂·ÛË Û ۇÁÎÚÈÛË Ì ·˘Ù¿ Ù˘ ÔÌ¿‰·˜ ÂϤÁ¯Ô˘ ‚ÏËÙÒÓ Ô˘ Û˘Ì‚¿ÏÏÔ˘Ó ÛÙËÓ Èı·ÓfiÙËÙ· ÂÈ‚›ˆÛ˘ (p=0,025 Î·È p=0,007 ·ÓÙ›ÛÙÔȯ·, ™¯. 2). Δ· ›‰· ¤ÁÈÓ Ì ٷ ÌÔÓ٤Ϸ ηٿ Cox. ™ÙËÓ ÔÏ˘·Ú·ÁÔÓÙÈ- ÙˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ·˘ÙÒÓ ‰ÂÓ ‰È·ÊÔÚÔÔÈ‹ıËÎ·Ó ÌÂ- ΋ ·Ó¿Ï˘ÛË ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó ÔÈ ÛÙ·ÙÈÛÙÈο ÛËÌ·- Ù¿ ÙËÓ Â¤Ì‚·ÛË. ∂›Û˘ ÛÙ·ıÂÚ¿ ·Ú¤ÌÂÈÓ·Ó Ù· ›- ÓÙÈΤ˜ ·Ú¿ÌÂÙÚÔÈ ·fi ÙË ÌÔÓÔ·Ú·ÁÔÓÙÈ΋ ·Ó¿Ï˘- ‰· ÙˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ Ù‡Ô˘ IgA ¤Ó·ÓÙÈ Ù˘ ÛË. ™ÙËÓ ÔÏ˘·Ú·ÁÔÓÙÈ΋ ·Ó¿Ï˘ÛË ‰ÂÓ ¯ÚËÛÈÌÔÔÈ- Ì˘ÔÛ›Ó˘ ÙfiÛÔ ÚÈÓ fiÛÔ Î·È ÌÂÙ¿ ÙËÓ Â¤Ì‚·ÛË ‹ıËÎ·Ó ¿Óˆ ·fi ÙÚÂȘ ÌÂÙ·‚ÏËÙ¤˜. ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ÔÚıÔÎÔÏÈÎfi ηÚΛÓÔ Î·È Ù· ÔÔ›· ‰ÂÓ ‰È·ÊÔÚÔÔÈ‹ıËÎ·Ó ·fi Ù· ›‰· Ô˘ ·Ú·ÙË- ∞ÔÙÂϤÛÌ·Ù· Ú‹ıËÎ·Ó ÛÙÔ˘˜ ˘ÁÈ›˜ ÂıÂÏÔÓÙ¤˜. ∏ Èı·ÓfiÙËÙ· ÂÓÙ·ÂÙÔ‡˜ ÂÈ‚›ˆÛ˘ ÙˆÓ ·ÛıÂ- Δ· ̤۷ ›‰· ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ÔÚÔ‡ ¤Ó·ÓÙÈ ÛÙË ÓÒÓ Ô˘ Û˘ÌÂÚÈÂÏ‹ÊıËÛ·Ó ÛÙË ÌÂϤÙË ·Ó‹Ïı Û 64 ∞Ó›¯Ó¢ÛË ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Ù˘ Ì˘ÔÛ›Ó˘ Û ·ÛıÂÓ›˜ Ì ηÚΛÓÔ ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘
ÓÔ˜ ·ÚÈıÌfi˜ ÌÂÏÂÙÒÓ ÂÚÈÁÚ¿ÊÂÈ Î·È ¯·Ú·ÎÙËÚ›˙ÂÈ ıÔÏÔÁÈΤ˜ ·Ú¿ÌÂÙÚÔÈ ÙˆÓ ·ÛıÂÓÒÓ ·˘ÙÒÓ ·ÚÔ˘- ·˘ÙÔ·ÓÙÈÛÒÌ·Ù· ÛÙÔÓ Î·ÚΛÓÔ4,5. ªÂÙ¿ ÙËÓ ·Ó·ÁÓÒ- ÛÈ¿˙ÔÓÙ·È ÛÙÔÓ ›Ó·Î· 1. √È fiÁÎÔÈ Ù·ÍÈÓÔÌ‹ıËÎ·Ó ÚÈÛË ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÛÙÔ p53 Û ·ÛıÂÓ›˜ Ì ۇÌʈӷ Ì ÙËÓ Î·Ù¿ Duke Ù·ÍÈÓfiÌËÛË ÙÚÔÔÔÈË- ηÚΛÓÔ ÙÔ˘ Ì·ÛÙÔ‡6, ϤÌʈ̷ Burkitt7 Î·È Î·ÚΛÓÔ Ì¤ÓË fiˆ˜ ÚÔÙ›ÓÂÙ·È ·fi ÙÔ˘˜ Astler Î·È Coller18. ÙÔ˘ Ó‡ÌÔÓ·8, ·Ó·Ù‡¯ıËΠÌÈ· ‰È¢ڢÓfiÌÂÓË Ï›ÛÙ· πÛÙÔÏÔÁÈ΋ Ù˘ÔÔ›ËÛË ÙˆÓ fiÁÎˆÓ ¤ÁÈÓ Ì ‚¿ÛË ÙÔ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Û ·ÓÙÈÁfiÓ· Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Û‡ÛÙËÌ· Δ·ÍÈÓfiÌËÛ˘ ÙÔ˘ ¶·ÁÎfiÛÌÈÔ˘ √ÚÁ·ÓÈ- Ì fiÁÎÔ˘˜ (tumour-associated antigens, TAA), Û˘- ÛÌÔ‡ ÀÁ›·˜ (WHO)19. ø˜ ¯ÚÔÓÈ΋ ·ÊÂÙËÚ›· Ù˘ ÌÂÚÈÏ·Ì‚·ÓÔÌ¤ÓˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÛÙÔ HER-2/ ·Ú·ÎÔÏÔ‡ıËÛ˘ ÔÚ›ÛÙËÎÂ Ë Ë̤ڷ ÙÔ˘ ¯ÂÈÚÔ˘ÚÁ›- 9 neu ÛÙÔÓ Î·ÚΛÓÔ ÙÔ˘ Ì·ÛÙÔ‡ Î·È ¤Ó·ÓÙÈ ÛÙÔ ras Ô˘ ÔfiÙÂ Û˘ÏϤ¯ıËÎÂ Î·È ÙÔ ÚÒÙÔ ‰Â›ÁÌ· ÔÚÔ‡ ·fi 10 ÛÙÔÓ Î·ÚΛÓÔ ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘ , ηıÒ˜ Î·È ¤Ó·- ÂÚÈÊÂÚÈÎfi ·›Ì·. ŒÓ·Ó Ì‹Ó· ÌÂÙ¿ ÙËÓ Â¤Ì‚·ÛË Û˘Ï- ÓÙÈ Û ڈÙ½Ó˜ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙÔÓ Î˘ÙÙ·ÚÈÎfi Ϥ¯ıËΠÙÔ ‰Â‡ÙÂÚÔ ‰Â›ÁÌ· ÔÚÔ‡ ·›Ì·ÙÔ˜ ηٿ ÙË Î‡ÎÏÔ fiˆ˜ Ë Î˘ÎÏ›ÓË μ1 ÛÙÔ Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛ- ‰È¿ÚÎÂÈ· Ù˘ ÚÔÁÚ·ÌÌ·ÙÈṲ̂Ó˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ 11 ӈ̷ . ÚÔ˘Ù›Ó·˜ ÙˆÓ ·ÛıÂÓÒÓ. ∏ ÌÂϤÙË ÔÏÔÎÏËÚÒıËΠ™ÙÔÓ ÔÚıÔÎÔÏÈÎfi ηÚΛÓÔ ¤¯Ô˘Ó ‹‰Ë ÂÚÈÁÚ·- ÛÙÔ˘˜ 62 Ì‹Ó˜ ÂÓÒ Ô Ì¤ÛÔ˜ fiÚÔ˜ ·Ú·ÎÔÏÔ‡ıËÛ˘ Ê› ¿Óˆ ·fi ‰¤Î· ·ÓÙÈÁfiÓ· Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙÔÓ ‹Ù·Ó 48 Ì‹Ó˜. fiÁÎÔ (Δ∞∞) Î·È ÂÚÈÛÛfiÙÂÚÔÈ ·fi 35 ·ÓÙÈÁÔÓÈÎÔ› ∏ ÔÌ¿‰· ÂϤÁ¯Ô˘ ·ÔÙÂÏÔ‡ÓÙ·Ó ·fi 16 ¿Ó‰Ú˜ ›ÙÔÔÈ Ù¿Í˘ π MHC12,13. ∞˘ÙÔ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ Î·È 6 Á˘Ó·›Î˜ Ì ̤ÛÔ fiÚÔ ËÏÈΛ·˜ Ù· 60 ¤ÙË ÛÙËÓ ·ÎÙ›ÓË Î·È ÙË Ì˘ÔÛ›ÓË, ‚·ÛÈο Û˘ÛÙ·ÙÈο ÙÔ˘ (SD±10,9). ◊Ù·Ó fiÏÔÈ ‰fiÙ˜ ·›Ì·ÙÔ˜ Ô˘ ÂÈϤ¯ıË- ΢ÙÙ·ÚÔÛÎÂÏÂÙÈÎÔ‡ ‰ÈÎÙ‡Ô˘ Î·È Ù˘ ΢ÙÙ·ÚÈ΋˜ ΛÓË- Î·Ó Ù˘¯·›· ·fi ÙË ªÔÓ¿‰· ªÂÙ¿ÁÁÈÛ˘ ∞›Ì·ÙÔ˜ Î·È Û˘ Î·È Î·Ù¿ Û˘Ó¤ÂÈ· Î·È Ù˘ ΢ÙÙ·ÚÈ΋˜ ‰È‹ıËÛ˘ ηٿ ÙËÓ ÂͤÏÈÍË ÙÔ˘ ηÚΛÓÔ˘, ¤¯Ô˘Ó ÂÚÈÁÚ·Ê› Û ÔÈ ÔÔ›ÔÈ ‰ÂÓ Â›¯·Ó ÈÛÙÔÚÈÎfi ·˘ÙÔ¿ÓÔÛ˘ ÓfiÛÔ˘ ·ÛıÂÓ›˜ Ì ¯ÚfiÓÈ· ÂÓÂÚÁfi Ë·Ù›Ùȉ· Î·È ·ÓÔÛÔÔÈ- ηÈ/‹ ‰ÂÓ Â›¯·Ó Ï¿‚ÂÈ ·ÓÔÛÔηٷÛÙ·ÏÙÈ΋ ıÂڷ›·. ËÙÈ΋ Ì˘Ôηډ›Ùȉ·14,15. ∂›Û˘ ÔÏϤ˜ ·Ó·ÊÔÚ¤˜ ¤- ∏ ̤ÛË ËÏÈΛ· Î·È Ë Î·Ù·ÓÔÌ‹ ÙˆÓ ÂıÂÏÔÓÙÒÓ ·Ó·- ¯Ô˘Ó ‰Â›ÍÂÈ ÙËÓ ‡·ÚÍË ·ÓÙÈ-˘ÚËÓÈÎÒÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ÊÔÚÈο Ì ÙÔ Ê‡ÏÔ Î·È ÙËÓ ËÏÈΛ· ‰ÂÓ ‰È¤ÊÂÚ ÛËÌ·- Û ‰È¿ÊÔÚ˜ ηÎÔ‹ıÂȘ, Û˘ÌÂÚÈÏ·Ì‚·ÓÔÌ¤ÓˆÓ ÙÔ˘ ÓÙÈο ·Ó¿ÌÂÛ· ÛÙȘ ÔÌ¿‰Â˜ ·ÛıÂÓÒÓ Î·È ÂϤÁ¯Ô˘ 2 ηÚΛÓÔ˘ ÙÔ˘ Ó‡ÌÔÓ· Î·È ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘16,17. (p=0,241, ¯ ¤ÏÂÁ¯Ô˜ ÁÈ· ʇÏÔ p=1). ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË ‰ÈÂÚ¢ӋıËÎÂ Ë ‡·ÚÍË ÂχıÂÚˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Ù˘ Ì˘ÔÛ›Ó˘ Ù‡- ªÂıÔ‰ÔÏÔÁ›· Ô˘ IgG, IgM, IgA, Û ÔÚfi ·ÛıÂÓÒÓ Ì ÔÚıÔÎÔÏÈÎfi ηÚΛÓÔ Ì ÛÎÔfi Ë ·ÚÔ˘Û›· ÙÔ˘˜ Ó· Û˘Û¯ÂÙÈÛı› ª¤ÙÚËÛË ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÛÙË Ì˘ÔÛ›ÓË Ì ٷ ÎÏÈÓÈÎÔ·ıÔÏÔÁÈο ¯·Ú·ÎÙËÚÈÛÙÈο Î·È ÙËÓ ÂÈ- Ì ÙËÓ Ù¯ÓÈ΋ ELISA ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ. ¶Ï¿Î˜ ELISA ÂÈÛÙÚÒıËÎ·Ó Ì 1 mg/ml Ì˘ÔÛ›Ó˘ Û PBS Î·È ·ÊÔ‡ ˆ¿ÛıËÎ·Ó ÁÈ· 12 ÒÚ˜ ÛÙÔ˘˜ ∞ÛıÂÓ›˜ 40C, ÍÂχıËÎ·Ó ÙÚÂȘ ÊÔÚ¤˜ Ì ‰È¿Ï˘Ì· 3% BSA Û PBS. √ ÔÚfi˜ ÙˆÓ ·ÛıÂÓÒÓ ÚÔÛÙ¤ıËΠÛÙȘ ÂÈ- ∏ ÌÂϤÙË Ú·ÁÌ·ÙÔÔÈ‹ıËΠۇÌʈӷ Ì ÙË ‰È·Î‹- ÛÙڈ̤Ó˜ ϿΘ Û ·Ú·›ˆÛË 1:100 Û 1% BSA Û ڢÍË ÙÔ˘ ∂ÏÛ›ÓÎÈ. ¢Â›ÁÌ·Ù· ÔÚÔ‡ ÂÏ‹ÊıËÛ·Ó ·fi 22 PBS Î·È Âˆ¿ÛıËΠ۠ıÂÚÌÔÎÚ·Û›· ‰ˆÌ·Ù›Ô˘ ÁÈ· ˘ÁÈ›˜ ‰fiÙ˜ Î·È ·fi 20 ·ÛıÂÓ›˜ Ì ڈÙÔÁÂÓ‹ ÔÚ- ıÔÎÔÏÈÎfi ηÚΛÓÔ Ô˘ ¯ÂÈÚÔ˘ÚÁ‹ıËÎ·Ó ÛÙËÓ ∞′ 90 ÏÂÙ¿. ŸÏ· Ù· ‰Â›ÁÌ·Ù· ·Ó·Ï‡ıËÎ·Ó ÂȘ ÙÚÈÏÔ‡Ó. ¶ÚÔ·È‰Â˘ÙÈ΋ ÃÂÈÚÔ˘ÚÁÈ΋ ∫ÏÈÓÈ΋ Ù˘ π·ÙÚÈ΋˜ ™¯Ô- ™ÙË Û˘Ó¤¯ÂÈ· ÔÈ Ï¿Î˜ ·ÊÔ‡ ÍÂχıËÎ·Ó ÙÚÂȘ ÊÔ- Ï‹˜ ÙÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ Î·Ù¿ ÙË ¯ÚÔÓÈ΋ Â- Ú¤˜ Ì ‰È¿Ï˘Ì· 1% BSA 0,5% Tween-20 Û PBS, Â- Ú›Ô‰Ô 2000-2002. ªÂÙ¿ ÙË Û˘ÏÏÔÁ‹ ÙÔ˘˜ Ù· ‰Â›ÁÌ·Ù· ˆ¿ÛÙËÎ·Ó Ì 1 Ìg/ml ·Óٛۈ̷ IgG ‹ IgA ‹ IgM Û˘- ÔÚÔ‡ Û˘ÓÙËÚ‹ıËÎ·Ó Û ıÂÚÌÔÎÚ·Û›· -80Ô C ̤¯ÚÈ ˙¢Á̤ÓÔ Ì ˘ÂÚÔÍÂȉ¿ÛË ‰È·Ï˘Ì¤ÓÔ Û 1% BSA Û ÙËÓ ·Ó¿Ï˘Û‹ ÙÔ˘˜. ∫·Ó›˜ ·fi ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ Û˘- PBS ÁÈ· 90 ÏÂÙ¿ Û ıÂÚÌÔÎÚ·Û›· ‰ˆÌ·Ù›Ô˘. ªÂÙ¿ ÌÂÚÈÏ‹ÊıËÎ·Ó ÛÙËÓ ¤Ú¢ӷ ‰ÂÓ Â›¯Â ÚÔËÁÔ‡ÌÂÓÔ ·fi ÙÚÂȘ χÛÂȘ Ì ‰È¿Ï˘Ì· 1% BSA 0,5% Tween- ÈÛÙÔÚÈÎfi ‹ ÎÏÈÓÈο ¯·Ú·ÎÙËÚÈÛÙÈο ·˘ÙÔ¿ÓÔÛ˘ Ófi- 20 Û PBS, 100 Ìl ‰È·Ï‡Ì·ÙÔ˜ ˘ÔÛÙÚÒÌ·ÙÔ˜ (0,5 ÛÔ˘ ηÈ/‹ ‰ÂÓ Â›¯Â Ï¿‚ÂÈ ıÂڷ›· Ô˘ ı· ÌÔÚÔ‡Û mg/ml O-Ê·ÈÓ˘ÏÂÓԉȷ̛ÓË-OPD Û 0,1 ª ∫ÈÙÚÈÎÔ‡ Ó· ¤¯ÂÈ Ô‰ËÁ‹ÛÂÈ Û ·ÓÔÛÔÏÔÁÈ΋ ·fiÎÚÈÛË. ¡·ÙÚ›Ô˘ pH=5, 1 Î·È 3% H2O2) ÚÔÛÙ¤ıËÎ·Ó Û ο- ∏ ÔÌ¿‰· ÙˆÓ ·ÛıÂÓÒÓ Ì ÔÚıÔÎÔÏÈÎfi ηÚΛÓÔ ı ԋ. ∏ ·ÓÙ›‰Ú·ÛË ‰ÈÂÎfiË Ì 1 ¡ HCI Î·È ÌÂ- ·ÔÙÂÏÔ‡ÓÙ·Ó ·fi 15 ¿Ó‰Ú˜ Î·È 5 Á˘Ó·›Î˜ Ì ̤- ÙÚ‹ıËÎÂ Ë ÔÙÈ΋ ˘ÎÓfiÙËÙ· ÛÙ· 492 nm Û Ì˯¿- ÛÔ fiÚÔ ËÏÈΛ·˜ Ù· 63 ¤ÙË (SD±11,29). √È ÎÏÈÓÈÎÔ·- ÓËÌ· ·Ó¿ÁÓˆÛ˘ ELISA. EÚ¢ÓËÙÈ΋ ÂÚÁ·Û›·
∞Ó›¯Ó¢ÛË ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Ù˘ Ì˘ÔÛ›Ó˘ Û ·ÛıÂÓ›˜ Ì ηÚΛÓÔ ÙÔ˘ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘
Z. ¶·ÏÏ·ÓÙ˙¿1, M. ¡ÈÎÔÏÔÔ‡ÏÔ˘2, N. ª¤ÌÔ˜2, A. K·Ù¿ÎË2, °. ∫·Ú·ÓÙ˙›ÎÔ˜2, ¡. AÏÂÍ·Ó‰ÚfiÔ˘ÏÔ˜1, °. ¶·Ó¤ÙÛÔ˜3, ª. KˆÓÛÙ·ÓÙÔ˘Ï¿Î˘2
1 ∂ÚÁ·ÛÙ‹ÚÈÔ μÈÔ¯ËÌ›·˜, πÔÎÚ¿ÙÂÈÔ ¡ÔÛÔÎÔÌ›Ô, ∞ı‹Ó· 2 ∂ÚÁ·ÛÙ‹ÚÈÔ ÃÂÈÚÔ˘ÚÁÈ΋˜ ŒÚ¢ӷ˜, ∞′ ¶ÚÔ·È‰Â˘ÙÈ΋ ÃÂÈÚÔ˘ÚÁÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ, πÔÎÚ¿ÙÂÈÔ ¡ÔÛÔÎÔÌÂ›Ô 3 ÃÂÈÚÔ˘ÚÁÈ΋ ∫ÏÈÓÈ΋, πÔÎÚ¿ÙÂÈÔ ¡ÔÛÔÎÔÌ›Ô
2009; 1: 63 – 59
¶∂ƒI§∏æ∏
∏ Û˘Û¯¤ÙÈÛË Ù˘ ÓÂÔÏ·Û›·˜ Ì ÙËÓ ·˘ÙÔ·ÓÔÛ›· ¤¯ÂÈ Ô‰ËÁ‹ÛÂÈ ÛÙË ÌÂϤÙË Ù˘ ¤ÎÊÚ·Û˘ ‰È·ÊfiÚˆÓ ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ Û ηÚÎÈ- ÓÔ·ı›˜ ÂχıÂÚÔ˘˜ ·fi ÂÌÊ·Ó¤˜ ·˘ÙÔ¿ÓÔÛÔ ÓfiÛËÌ·. ™ÙËÓ ·ÚÔ‡Û· ÌÂϤÙË, ÌÂÙÚ‹ıËÎ·Ó Ì ‰ÔÎÈÌ‹ ÂÓ˙˘Ì·ÙÈ΋˜ ·ÓÔÛÔ·- ÔÚÚfiÊËÛ˘ (ELISA) ÂχıÂÚ· ΢ÎÏÔÊÔÚÔ‡ÓÙ· ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ Ù˘ Ì˘ÔÛ›Ó˘ Ù‡Ô˘ IgG, IgM Î·È IgA Û 20 ·ÛıÂÓ›˜ ¿Û¯Ô- ÓÙ˜ ·fi ÔÚıÔÎÔÏÈÎfi ηÚΛÓÔ Ô˘ ˘Ô‚Ï‹ıËÎ·Ó Û ¯ÂÈÚÔ˘ÚÁÈ΋ ÂÍ·›ÚÂÛË ÙÔ˘ fiÁÎÔ˘, ÚÈÓ ÙËÓ Â¤Ì‚·ÛË Î·È ¤Ó· Ì‹Ó· ÌÂÙ¿. ™ÙË ÌÂϤÙË Û˘ÌÂÚÈÏ‹ÊıËÛ·Ó Î·È 22 ˘ÁÈ›˜ ÂıÂÏÔÓÙ¤˜ ·ÈÌÔ‰fiÙ˜ ˆ˜ ÔÌ¿‰· ÂϤÁ¯Ô˘. √È ÌÂÙÚ‹ÛÂȘ ÛÙË Û˘Ó¤¯ÂÈ· Û˘Û¯ÂÙ›ÛÙËÎ·Ó Ì ٷ ÎÏÈÓÈÎÔ·ıÔÏÔÁÈο ¯·Ú·ÎÙËÚÈÛÙÈο Î·È ÙËÓ ÂÓÙ·ÂÙ‹ ÂÈ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ. Δ· ·ÔÙÂϤÛÌ·Ù· ¤‰ÂÈÍ·Ó ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÛÙË Ì¤ÛË ÙÈÌ‹ ÙˆÓ Î˘ÎÏÔÊÔÚÔ‡ÓÙˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Ù˘ IgM ·ÓÙÈ-Ì˘ÔÛ›Ó˘ ÌÂÙ¿ ÙË ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË ÙfiÛÔ ÚÈÓ (p=0,001) fiÛÔ Î·È (p=0,002) Û ۇÁÎÚÈÛË Ì ÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘. ∞ÓÙ›ıÂÙ· Ë Ì¤ÛË ÙÈÌ‹ ÙˆÓ ·ÓÙÈÛÙÔ›¯ˆÓ IgG ·ÓÙÈÛˆÌ¿ÙˆÓ ·˘Í‹ıËΠÛÙ·- ÙÈÛÙÈÎÒ˜ ÛËÌ·ÓÙÈο ÙfiÛÔ ÚÈÓ (p=0,027) fiÛo Î·È ÌÂÙ¿ (p=0,007) ÙÔ ¯ÂÈÚÔ˘ÚÁÂ›Ô Û ۯ¤ÛË Ì ÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘. √È ·ÛıÂÓ›˜ Ô˘ ·ÚÔ˘Û›·Û·Ó ·˘ÍË̤ӷ ›‰· ·ÓÙÈÛˆÌ¿ÙˆÓ IgG ·ÓÙÈ-Ì˘ÔÛ›Ó˘ ›¯·Ó ηχÙÂÚË ÚfiÁÓˆÛË fiˆ˜ ·Ô‰Â›¯ıËÎÂ Î·È Ì ÙËÓ ·Ó¿Ï˘ÛË ·ÏÈÓ‰ÚfiÌËÛ˘ ηٿ Cox. √È ·ÏÏ·Á¤˜ ÛÙ· ›‰· ÙˆÓ ÂχıÂÚˆÓ Î˘ÎÏÔÊÔÚÔ‡ÓÙˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ Ù˘ Ì˘ÔÛ›Ó˘ Ô˘ ÂÚÈÁÚ¿ÊÔÓÙ·È ÛÙËÓ ·ÚÔ‡Û· ÌÂϤÙË Ê·›ÓÂÙ·È Ó· ·ÔÙÂÏÔ‡Ó Ê˘ÛÈΤ˜ ·ÓÙȉڿÛÂȘ ÙÔ˘ ·ÓÔÛÈ·ÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ Èı·ÓÒ˜ ·- ÁfiÌÂÓ˜ ·fi ÂȉÈο ·ÓÙÈÁfiÓ· ÙˆÓ ÓÂÔÏ·ÛÌ·ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ.
§¤ÍÂȘ-ÎÏÂȉȿ: ∞˘ÙÔ·ÓÙÈÛÒÌ·Ù·, ELISA, ª˘ÔÛ›ÓË, ηÚΛÓÔ˜ ·¯¤Ô˜ ÂÓÙ¤ÚÔ˘.
2,3 ∂ÈÛ·ÁˆÁ‹ ÙÔÏÔÁÈΤ˜ ÓÂÔϷۛ˜ . Δ· ·˘ÙÔ·ÓÙÈÁfiÓ· ·Ó·ÁÓˆÚ›- ˙ÔÓÙ·È ·fi Ï¢ÎÔ΢ÙÙ·ÚÈÎÔ‡˜ ˘Ô‰Ô¯Â›˜, ÂÓÂÚÁÔÔÈ- ™Â ÔÏϤ˜ ÂÚÈÙÒÛÂȘ ηÚΛÓÔ˘ ·Ú·ÙËÚÔ‡ÓÙ·È Ê·È- ÒÓÙ·˜ ÙË ¯˘ÌÈ΋ ·ÓÔÛ›·. ΔÌ‹Ì·Ù· ηÙÂÛÙÚ·Ì̤ÓÔ˘ ÓfiÌÂÓ· ·˘ÙÔ·ÓÔÛ›·˜ Ì ÙÔÓ Û¯ËÌ·ÙÈÛÌfi ·ÓÙÈۈ̿- ÈÛÙÔ‡ ÌÔÚ› Ó· ÚÔηϤÛÔ˘Ó ·˘ÙÔ·ÓÔÛ›· ÌfiÓÔ ÙˆÓ ¤Ó·ÓÙÈ Û ·˘ÙfiÏÔÁ· ΢ÙÙ·ÚÈο ·ÓÙÈÁfiÓ·1. ¶·Ú·- fiÙ·Ó ÙÔ ·ÓÔÛÈ·Îfi Û‡ÛÙËÌ· Â›Ó·È ·ÔÚÚ˘ıÌÈṲ̂ÓÔ ÁfiÌÂÓ· ·˘ÙÔ·ÓÙÈÛÒÌ·Ù· ¤¯Ô˘Ó ÂÓÙÔÈÛÙ› ÙfiÛÔ ÛÙÔÓ ‹/Î·È Î·Ù·ÛÙ·Ï̤ÓÔ. ÔÚfi ·ÛıÂÓÒÓ ÌÂ Û˘Ì·Á›˜ fiÁÎÔ˘˜ fiÛÔ Î·È Ì ·ÈÌ·- Δ· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ¤Ó·˜ ÔÏÔ¤Ó· Î·È ·˘Í·ÓfiÌÂ- √¢∏°π∂™ °π∞ Δ√À™ ™À°°ƒ∞º∂π™
ΔÔ ÂÚÈÔ‰ÈÎfi «∞ÓÔÛ›·» ÂΉ›‰ÂÙ·È ·fi ÙËÓ ∂ÏÏË- Ù‡Ô˘ ∞4, Ì ‰ÈÏfi ‰È¿ÛÙËÌ· Î·È ÂÚÈıÒÚÈ·, ÂÓÒ ÔÈ ÓÈ΋ ∂Ù·ÈÚ›· ∞ÓÔÛÔÏÔÁ›·˜ Î·È ·ÔÙÂÏ› ÙÔ Ì¤ÛÔ ÁÚ·ÌÌ·ÙÔÛÂÈÚ¤˜ Ô˘ Ú¤ÂÈ Ó· ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Â›- ÚÔÒıËÛ˘ Ù˘ ·ÓÔÛÔÏÔÁ›·˜ ÛÙÔ˘˜ ¯ÒÚÔ˘˜ ‰ÈÂÍ·- Ó·È ÔÈ Times New Roman Î·È Arial. ÁˆÁ‹˜ È·ÙÚÈ΋˜ ¤Ú¢ӷ˜ Î·È ÎÏÈÓÈ΋˜ Ú¿Í˘. ™ÙÔ Â- ∞ÔÙÂÏÔ‡Ó Í¯ˆÚÈÛÙ¤˜ ÂÓfiÙËÙ˜ Î·È Ú¤ÂÈ Ó· ˘Ô- ÚÈÔ‰ÈÎfi ‰ËÌÔÛȇÔÓÙ·È ¿ÚıÚ· Û‡ÓÙ·Í˘, ·Ó·ÛÎÔÈο ‚¿ÏÏÔÓÙ·È Û ȉȷ›ÙÂÚË ÛÂÏ›‰·: ¿ÚıÚ·, ÂÚ¢ÓËÙÈΤ˜ Î·È ¿ÏϘ ÚˆÙfiÙ˘Â˜ ÂÚÁ·Û›Â˜, ∞) O Ù›ÙÏÔ˜ Ù˘ ÂÚÁ·Û›·˜ Ì ٷ ÔÓfiÌ·Ù· ÙˆÓ Û˘Á- ÂӉȷʤÚÔ˘Û˜ ÂÚÈÙÒÛÂȘ Î·È ÁÚ¿ÌÌ·Ù· ·fi Î·È ÁڷʤˆÓ, ÙÔ ›‰Ú˘Ì· ·fi ÙÔ ÔÔ›Ô ÚÔ¤Ú¯ÔÓÙ·È ÚÔ˜ ÙË Û‡ÓÙ·ÍË. Î·È ÙË ‰È‡ı˘ÓÛË ÙÔ˘ Û˘ÁÁڷʤ· ÁÈ· ·ÏÏËÏÔÁÚ·- Ê›·. ÀÔ‚ÔÏ‹ ¿ÚıÚˆÓ: Δ· ¿ÚıÚ· ·ÔÛÙ¤ÏÏÔÓÙ·È μ) ∏ ÂÚ›ÏË„Ë Ù˘ ÂÚÁ·Û›·˜ (Ì ÙËÓ ·Ó¿ÏÔÁË ‰ÔÌ‹), ÛÙÔÓ ÂΉfiÙË ÛÙË ‰È‡ı˘ÓÛË: Ë ÔÔ›· ‰ÂÓ Ú¤ÂÈ Ó· ˘ÂÚ‚·›ÓÂÈ ÙȘ 200 ϤÍÂȘ, ¶. ªÔ‡Ú· Ì·˙› Ì 3-5 ϤÍÂȘ-ÎÏÂȉȿ. °È· ÙÔ ÂÚÈÔ‰ÈÎfi ∞¡O™π∞ °) ΔÔ Î›ÌÂÓÔ Ù˘ ÂÚÁ·Û›·˜. ™ÙȘ ÂÚ¢ÓËÙÈΤ˜ ÂÚÁ·Û›Â˜ ΔÌ‹Ì· ∫ÏÈÓÈ΋˜ ∞ÓÔÛÔÏÔÁ›·˜ ·ÎÔÏÔ˘ıÂ›Ù·È Ë ÛÂÈÚ¿: ÂÈÛ·ÁˆÁ‹, ˘ÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ, ′ μ ¶·ıÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ∞¶£ ·ÔÙÂϤÛÌ·Ù· Î·È Û˘˙‹ÙËÛË. ∂¿Ó ÚfiÎÂÈÙ·È ÁÈ· ÎÏÈÓÈ- ∫ˆÓÛÙ·ÓÙÈÓÔ˘fiψ˜ 49, ΋ ÌÂϤÙË, ÙfiÙ ڤÂÈ Ó· ·Ó·Ê¤ÚÂÙ·È fiÙÈ Ú·ÁÌ·- 546 42 πÔÎÚ¿ÙÂÈÔ °.¡.¶.£. ÙÔÔÈ‹ıËΠۇÌʈӷ Ì ÙË ‰È·Î‹Ú˘ÍË ÙÔ˘ ∂ÏÛ›ÓÎÈ. £ÂÛÛ·ÏÔÓ›ÎË OÈ Ê·Ú̷΢ÙÈΤ˜ Ô˘Û›Â˜ ·Ó·Ê¤ÚÔÓÙ·È Ì ÙËÓ ÎÔÈ- °È· οıÂ Ù‡Ô ¿ÚıÚÔ˘ ÈÛ¯‡Ô˘Ó ȉȷ›ÙÂÚ˜ Ô‰Ë- Ófi¯ÚËÛÙË Î·È fi¯È ÙËÓ ÂÌÔÚÈ΋ ÔÓÔÌ·Û›· ÙÔ˘˜. Á›Â˜: ¢) O Ù›ÙÏÔ˜ Ù˘ ÂÚÁ·Û›·˜ Ì ٷ ÔÓfiÌ·Ù· ÙˆÓ Û˘Á- 1. ÕÚıÚ· Û‡ÓÙ·Í˘: ™˘ÓÔÙÈο ¿ÚıÚ· Ô˘ ‰ÂÓ ˘ÂÚ- ÁڷʤˆÓ, Ù· ·ÓÙ›ÛÙÔȯ· ȉڇ̷ٷ ·’ fiÔ˘ ÚÔ- ‚·›ÓÔ˘Ó ÙȘ 2 ÛÂÏ›‰Â˜. ∏ ¤ÎÙ·Û‹ ÙÔ˘˜ ‰ÂÓ Ú¤ÂÈ ¤Ú¯ÔÓÙ·È, ÙÔ Î›ÌÂÓÔ Ù˘ ÂÚ›Ï˄˘ Î·È ÙȘ ϤÍÂȘ- Ó· ˘ÂÚ‚·›ÓÂÈ ÙȘ 500 ϤÍÂȘ. ÎÏÂȉȿ ÛÙËÓ ∞ÁÁÏÈ΋. 2. ÕÚıÚ· ·Ó·ÛÎÔÈο: ¶ÚfiÎÂÈÙ·È ÁÈ· Û‡ÓıÂÙË ·- ∂) OÈ ‚È‚ÏÈÔÁÚ·ÊÈΤ˜ ·Ú·Ô̤˜. ÚÔ˘Û›·ÛË ÂÓfi˜ ı¤Ì·ÙÔ˜ Ô˘ ÂÚÈÏ·Ì‚¿ÓÂÈ ÙËÓ Âͤ- ™Δ) OÈ ˘fiÙÈÙÏÔÈ ÙˆÓ ÂÈÎfiÓˆÓ Î·È ÔÈ ÂÂÍËÁ‹ÛÂȘ ÙˆÓ ÏÈÍ‹ ÙÔ˘ ̤¯ÚÈ Û‹ÌÂÚ· ·ÏÏ¿ ΢ڛˆ˜ ÙȘ ÓÂfiÙÂÚ˜ Û¯ËÌ¿ÙˆÓ Î·È ÈӿΈÓ. ∫¿ı ˘fiÙÈÙÏÔ˜ ·Ú·Ù›ıÂ- ·fi„ÂȘ Î·È ÚÔÔÙÈΤ˜. ΔÔ Ì¤ÁÂıÔ˜ ÙÔ˘ ¿ÚıÚÔ˘ Ù·È Û Í¯ˆÚÈÛÙ‹ ÛÂÏ›‰·. ‰ÂÓ Ú¤ÂÈ Ó· ˘ÂÚ‚·›ÓÂÈ ÙȘ 4.000 ϤÍÂȘ. ∑) OÈ ›Ó·Î˜, Û¯‹Ì·Ù· Î·È ÂÈÎfiÓ˜ Ô˘ ‰˘Ó·Ùfi Ó· 3. ∂Ú¢ÓËÙÈΤ˜, ÚˆÙfiÙ˘Â˜ ÂÚÁ·Û›Â˜: Œ¯Ô˘Ó ÎÏÈÓÈÎfi Û˘ÓÔ‰Â‡Ô˘Ó ÙÔ Î›ÌÂÓÔ Î·È Ú¤ÂÈ Ó· ·Ú·Ù›ıÂ- ‹ ÂÚÁ·ÛÙËÚÈ·Îfi ¯·Ú·ÎÙ‹Ú· ‹ ·ÔÙÂÏÔ‡Ó ÚÔ˚fiÓ ÓÙ·È Û Í¯ˆÚÈÛÙ¤˜ ÛÂÏ›‰Â˜. OÈ ÂÈÎfiÓ˜ Ú¤ÂÈ Ó· ‚·ÛÈ΋˜ ¤Ú¢ӷ˜, ÂÓÒ Ë ‰ÔÌ‹ ÙÔ˘˜ Ú¤ÂÈ Ó· Â- ¤¯Ô˘Ó ·Ó¿Ï˘ÛË 300 dpi ÙÔ˘Ï¿¯ÈÛÙÔÓ. ÚÈÏ·Ì‚¿ÓÂÈ ÂÚ›ÏË„Ë, ÂÚÈÁÚ·Ê‹ ˘ÏÈÎÔ‡ Î·È ÌÂıÔ- °È· ÙËÓ ÂÚ›ÙˆÛË ÂÎÙ‡ˆÛ˘ ¤Á¯ÚˆÌˆÓ ÂÈÎfi- ‰ÔÏÔÁ›·˜, ·ÔÙÂϤÛÌ·Ù· Î·È Û˘˙‹ÙËÛË. ¢ÂÓ Ú¤- ÓˆÓ, Ô Û˘ÁÁڷʤ·˜ ı· ÂÓËÌÂÚÒÓÂÙ·È ·fi ÙË ™˘ÓÙ·- ÂÈ Ó· ˘ÂÚ‚·›ÓÔ˘Ó ÙȘ 3.500-4.000 ϤÍÂȘ. ÎÙÈ΋ ∂ÈÙÚÔ‹ ÁÈ· ÙË ‰È·ÊÔÚ¿ ÎfiÛÙÔ˘˜, ÙËÓ ÔÔ›· 4. ∂ӉȷʤÚÔ˘Û˜ ÂÚÈÙÒÛÂȘ: ¶·ÚÔ˘Û›·ÛË ÂÚÈ- Î·È ı· ·Ó·Ï·Ì‚¿ÓÂÈ Ô ›‰ÈÔ˜ Ó· ηχ„ÂÈ. ÛÙ·ÙÈÎÒÓ Û¿ÓÈˆÓ Â›Ù ˆ˜ ÚÔ˜ ÙËÓ ÎÏÈÓÈÎÔÂÚÁ·- ÛÙËÚȷ΋ ÙÔ˘˜ ÔÚ›· ›Ù ˆ˜ ÚÔ˜ ÙË ıÂڷ¢ÙÈ- μÈ‚ÏÈÔÁÚ·ÊÈΤ˜ ·Ú·Ô̤˜: ΔÔ ÂÚÈÔ‰ÈÎfi ΋ ÙÔ˘˜ ·ÓÙÈÌÂÙÒÈÛË Î·È ÂͤÏÈÍË. Δ· ¿ÚıÚ· Ú¤- «∞ÓÔÛ›·» ·ÎÔÏÔ˘ı› ÙÔ Û‡ÛÙËÌ· Vancouver Û‡Ìʈ- ÂÈ Ó· Â›Ó·È 1.000-1.500 Ϥ͈Ó. Ó· Ì ÙÔ ÔÔ›Ô ÔÈ ·Ú·Ô̤˜ ÂÌÊ·Ó›˙ÔÓÙ·È ÛÙÔ Î›- 5. °Ú¿ÌÌ·Ù· ÚÔ˜ ÙË Û‡ÓÙ·ÍË: ¶ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ·Ó·- ÌÂÓÔ Ì ÌÔÚÊ‹ ·ÚÈıÌÒÓ. ∂ÊfiÛÔÓ ÔÈ Û˘ÁÁÚ·Ê›˜ ›- ÎÔÈÓÒÛÂȘ Úfi‰ÚÔÌˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ, ›Ù ۯfiÏÈ· Ó·È ÂÚÈÛÛfiÙÂÚÔÈ ·fi ¤ÍÈ, ·Ó·Ê¤ÚÔÓÙ·È ÔÈ 3 ÚÒÙÔÈ Ô˘ ·ÊÔÚÔ‡Ó ‰ËÌÔÛÈÂ˘Ì¤Ó· ÛÙÔ ÂÚÈÔ‰ÈÎfi ¿ÚıÚ·. Î·È ·ÎÔÏÔ˘ı› Ë Û‡ÓÙÌËÛË: Î·È Û˘Ó. ‹ et al. OÈ Û˘- ¢ÂÓ ı· Ú¤ÂÈ Ó· ˘ÂÚ‚·›ÓÔ˘Ó ÙȘ 500 ϤÍÂȘ. ÓÙÌ‹ÛÂȘ ÙˆÓ ÂÚÈÔ‰ÈÎÒÓ ·Ú·Ù›ıÂÓÙ·È Û‡Ìʈӷ Ì ÙÔ Abridged Index Medicus .¯. ™‡ÓÙ·ÍË ¯ÂÈÚÔÁڿʈÓ: Δ· ¿ÚıÚ· Ô˘ ·Ô- ªÔ‡Ú· ¶. ∞ÓÔÛȷ΋ ·fiÎÚÈÛË. ™ÙÔ: ΔÔ̤·˜ ¶·ıÔÏÔÁ›·˜, π·- ÛÙ¤ÏÏÔÓÙ·È ÛÙÔ ÂÚÈÔ‰ÈÎfi Ú¤ÂÈ Ó· Â›Ó·È ÁÚ·Ì̤ӷ ÙÚÈ΋ ™¯ÔÏ‹ ∞¶£, ∂ÛˆÙÂÚÈ΋ ¶·ıÔÏÔÁ›·, £ÂÛÛ·ÏÔÓ›- ÛÙË ÓÂÔÂÏÏËÓÈ΋ ‰ËÌÔÙÈ΋. ÀÔ‚¿ÏÏÔÓÙ·È Û ÛÂÏ›‰Â˜ ÎË, University Studio Press, 2004: 49-53. Boura P, Papadopoulos S, Tselios K, et al. Intracerebral hemor- ∂ÊfiÛÔÓ Ë ÂÚÁ·Û›· Â›Ó·È Ù˘Èο ÔÏÔÎÏËڈ̤ÓË rhage in a patient with SLE and catastrophic antipho- Û‡Ìʈӷ Ì ÙȘ ·Ú·¿Óˆ Ô‰ËÁ›Â˜ ÚÔˆıÂ›Ù·È ·fi spholipid syndrome (CAPS): report of a case. Clin Rhe- ÙËÓ ÂÈÙÚÔ‹ ÂÈ̤ÏÂÈ·˜ Û‡ÓÙ·Í˘ Û 2 ̤ÏË Ù˘ umatol 2005 Aug; 24(4): 420-4. Û˘Ì‚Ô˘Ï¢ÙÈ΋˜ ÂÈÙÚÔ‹˜. OÈ ÎÚÈÙ¤˜ οÓÔ˘Ó ‰ÂÎÙ‹ ‹ ŸÏ· Ù· ·Ú·¿Óˆ Û˘ÁÎÚÔÙÔ‡Ó ÙÔ Û˘ÓÔÏÈÎfi Λ- ·ÔÚÚ›ÙÔ˘Ó ÙËÓ ÂÚÁ·Û›·, ÂÓÒ ‰È·Ù˘ÒÓÔ˘Ó ÙȘ ·- ÌÂÓÔ ˘Ô‚ÔÏ‹˜ Î·È Ú¤ÂÈ ·˘Ùfi Ó· ·ÔÛÙ¤ÏÏÂÙ·È Û ڷÙËÚ‹ÛÂȘ ÙÔ˘˜ ÔÈ Ôԛ˜ ÂÈÛÙÚ¤ÊÔÓÙ·È Ì·˙› Ì ÙÚ›· ·ÓÙ›Ù˘· ÛÙÔÓ ÂΉfiÙË ÙÔ˘ ÂÚÈÔ‰ÈÎÔ‡, Ì·˙› Ì ÙËÓ ÂÚÁ·Û›· ÛÙÔ˘˜ Û˘ÁÁÚ·Ê›˜. ™ÙÔ ÛÙ¿‰ÈÔ Ù˘ ÙÂÏÈ- ÌÈ· ‰ÈÛΤٷ fiÔ˘ ı· ÂÚȤ¯ÂÙ·È Ë ÂÚÁ·Û›· Û ËÏÂÎ- ΋˜ Ê¿Û˘ Ù˘ ÂÎÙ‡ˆÛ˘ ·ÔÛÙ¤ÏÏÂÙ·È ÛÙÔ˘˜ Û˘Á- ÙÚÔÓÈ΋ ÌÔÚÊ‹. ÁÚ·Ê›˜ ÙÔ ÙÂÏÈÎfi ‰ÔΛÌÈÔ ÙÔ ÔÔ›Ô Âȉ¤¯ÂÙ·È Ï¤ÔÓ ∫¿ı ˘Ô‚ÔÏ‹ Ú¤ÂÈ Ó· Û˘Óԉ‡ÂÙ·È ·fi ÂÓ˘- ÌfiÓÔ ÔÚıÔÁÚ·ÊÈΤ˜ ‰ÈÔÚıÒÛÂȘ. ™ÙÔ ÛËÌÂ›Ô ·˘Ùfi Á›- fiÁÚ·ÊË ÂÈÛÙÔÏ‹ ÙÔ˘ ÚÒÙÔ˘ Û˘ÁÁڷʤ· fiÔ˘ ı· ÓÂÙ·È Î·È Ë ·Ú·ÁÁÂÏ›· ÙˆÓ ·Ó·Ù‡ˆÓ ·fi ÙÔ˘˜ Û˘Á- ‰ËÏÒÓÂÙ·È fiÙÈ Ë ÂÚÁ·Û›· ‰ÂÓ ‚Ú›ÛÎÂÙ·È Û ‰È·‰Èηۛ· ÁÚ·Ê›˜. ∂ÚÁ·Û›Â˜ Ô˘ ‰ËÌÔÛȇÔÓÙ·È ÛÙÔ ÂÚÈÔ‰ÈÎfi ÎÚ›Û˘ Î·È ‰ÂÓ ¤¯ÂÈ ‰ËÌÔÛÈ¢ı› ·fi ÔÔÈÔ‰‹ÔÙ «∞ÓÔÛ›·» ·ÔÙÂÏÔ‡Ó ÓÂ˘Ì·ÙÈ΋ ÙÔ˘ ȉÈÔÎÙËÛ›· Î·È Ë ¿ÏÏÔ ÂÚÈÔ‰ÈÎfi Î·È fiÙÈ fiÏÔÈ ÔÈ Û˘ÁÁÚ·Ê›˜ Û˘Ìʈ- ·Ó·‰ËÌÔÛ›Â˘ÛË Ì¤ÚÔ˘˜ ‹ ÔÏfiÎÏËÚÔ˘ ÙÔ˘ ÎÂÈ̤ÓÔ˘ ÓÔ‡Ó ÛÙËÓ Èı·Ó‹ ‰ËÌÔÛ›Â˘Û‹ Ù˘. ··ÈÙ› ÙËÓ ¤ÁÁÚ·ÊË Û˘ÁηٿıÂÛË ÙÔ˘ ÂΉfiÙË.