DOCSLIB.ORG

Igg SUBCLASS CONCENTRATIONS in CHILDREN in HEALTH and DISEASE

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Igg SUBCLASS CONCENTRATIONS in CHILDREN in HEALTH and DISEASE 2-5. j,92 IgG SUBCLASS CONCENTRATIONS IN CHILDREN IN HEALTH AND DISEASE A thesis submitted by LORRAINE JOYCE BEARD, M.B.,Ch.B., F.Rá,.C.P. to the Universitv of Adelaide. South Auitralia ' For the degree of DOCTOR OF MEDICII{E Ilepartuent of Paediatrics, University of Adelaide, South Australia AugusÇ 1990 TABLE OF CONTENTS PAGE NO. Ihesis Summary 8 Declaration 11 Acknowledgements 72 Abbreviations L4 Index of Tables L6 Index of Figurrcs 19 Preface 2I CHAPIER 1 -- Review of the literature 22 L.1- Introduction 23 L.2 Overview of imm unsgloþtrlins 23 1.2.1 Immunoglobulinstructure u t.2.L.2 Immunoglobnlin classes n t.2.2 Immunoglob'rlinGsubclasses 29 L.2.2.L Historical bacþround 29 L.2.2.2 Isotlpes of IgG subclass 31 1.2.2.3 Allotypes of IgG subclasses 3l L.2.2.4 Relative concentrations of IgG subclasses in serum 32 L.2.2.5 Properties of IgG subclasses 33 - Complement activation by IgG subclasses 33 - Placental passage of IgG subclasses % - Susceptibility of the IgG subclasses to dþestion with proteoþtic enz5@es 37 - Half-lives of IgG subclasses 37 - Cellular interactions of IgG subclasses TI L,3 Immunoglobulin production 38 1.3.1 B llmphocytes 38 L.3.2 Heary chain gene formation q L.3.3 The regulation of immunoglobulin production 43 L.3.3.L T cells 44 - T and B cell interactions 44 - T-independent and T-dependent antigens 6 - T cells and histocompatibility antþens 47 L.3.3.2 Macrophages 47 L.3.3.3 Natural killer cell 4{ì PAGE NO. L.3.4 Iinmunogenetrcs t.3.4.L Genes that influence the immune response 1.3.4.2 Genes and immunoglobulin isotlpe concent¡ations 1.3.4.3 Allot¡pes and disease 1.4 Evaluation of IgG subclass concent¡ations I.4.L Quantitation of IgG subclasses 7.4.2 Normal serum concent¡ations of IgG subclasses in child¡en 1.5 IgG subclass deficiency in IgA-deficient patients 1.6 IgG subclasses and'specifi.C antibodies I.6.I IgG subclass distribution of antibodies 1.6.1.1 Protein antþens 1.6.L.2 Carbohydrate antigens I.6.1.3 Other antþens L.6.L.4 gnmm¿¡y L.6.2 Proposed ¡ech¡nisms, of isotype restriction L.6.2.I Models for isotype restriction L.6.2.2 Factors that may influence the pattern of IgG subdass production L.7 IgG subclass concent¡ations in children with recurrent infections 1.8 IgG subdass concent¡ations in patients with recoenised im m unodefi ciency disorders 1.9 Immunoglobulin replacement therapy 1.9.1 Intraveuous immuneglsþulin preparations L.9.L.L Methods of preparation L.9.L.2 IgG subclass composition 1.9.1.3 Antibodycontent L.9.L.4 Complement activation L.9.2 The use qf immunogleþnlin replacement therapy i" IgG subclass-defi cient child¡en CHAPTER2 General Methods 2.L Immunoglobnlin quantitation 2.L.1 Selm IgA,IgG and IgM 2.L.2 Salivary IgA 2.t.3 Serum IgE 2.L.4 Antibody quantitation PAGE NO. 2.2 Cellular Studies 92 2.2.L Preparation of leucocytes yz 2.2.2 Neutrophil studies 94 2.2.2.L Neutrophil chemotaxis and random mobility 94 2.2.2.2 Quantitative leucocyte io,li"ation reaction 94 2.2.2.3 Neutrophil bactericidal and fungicidal activity 96 2.2.2.4 Neutrophil respiratory burst 96 2.2.3 Lymphocytestudies 97 2.2.3.1 Lymphocyte phenotlping 97 2.2.3.2 L¡mphocyte transformation to mitogens 98 2.2.3.3 In vitro immunoglobrlin production 98 2.2.3.4 NK cell cytotoxicity 99 2.2.4 Controls for cellula¡ studies 101 2.3 Complement 101 2.3.L Total haemolytic complement 101 2.3.2 Individualcomplementcomponents r0z 2.4 Statistical analyses L02 CHAPTER 3 - The development of an enz¡me-linked immunosorbent assay using monoclonal antibodies for the quantitation of þG subclasses 103 3.1 Rationale for developing an ELISA technique for IgG subdass quantitation 104 3.2 Rationale for using monoclonal antibodies 105 3.3 International reference standards for IgG subclasses 106 3.4 Overview of tÏe essential steps in ou¡ IgG subclass ELISA 106 3.5 Det¡ils of the IgG subclass ELISA L09 3.6 Accuracy of our ELISA TT4 3;7 Comparison with other recently developed ELISA methods for IgG subclass quantitation tt4 3.8 Alternatives to ELISA ].20 3.9 Comparison of RID and ELISA ûn 3.10 Comparison of preliminary results obtained with our ELISA with those of other investigators L20 3.11 Conclusion L22 PAGE NO. CHAPItsR 4 - Establishing norrnal ranges for þG subclass concentrations in healthy Australian children 123 4.L Introduction and preliminary studies 12+ 4.2 Subjects and statistical analysis 125 4.2.L Subjects 125 4.2.2 Statistic¿lanalysis 126 4.3 Results 126 4.4 Discussion 12ß 4.4.L Comparisons of paediatric normal rânges for IgG subclasses 126 4.4.2 Possible rearions for differences between studies VI 4.4.3 Conclusions 129 CIIAPIER 5 - ICG subclass deficiencies in lgA-delicient patients 150 5.1 Introduction 151 5.2 Patients and methods 152 5.3 Results 153 5.4 Summary L& CHAPIER 6 - IgG subclass deficiency in patients with bronchiectasis t67 6.L Introduction 168 6.2 Patients 168 6.3 Results L69 6.4 Sumnary t70 CHAPIER 7 - IgG subclass deficiencies in infants with invasive Haemophilus influenzoe type b lnfections L76 7.L Int¡oduction t77 7.2 Patients 177 7.3 Results L79 7.4 Summary 184 CHAPIER I - IgG subclasses in osteomyelitis and septic arthritis 185 8.1 Introduction 186 PAGE NO. 8.2 Patients 186 8.3 Results 188 8.4 Sunmary 188 CHAPIER 9 - IgG subclass concentrations in children with giardiasis 9.1 Introduction 9.2 Patients 9.3 Results 9.4 Srrmmary - IgG subclass concentrations in patients with immunological disorders 10.1 Introduction L0.2 Patients 10.3 Results ro.4 $nmm¿ry - The influence of the spleen on serum IgG subclass concenhations 1_l-.1 Int¡oduction tL.2 Patients tl.3 Results LL.4 Summary - IgC subclasses and immunoglobulin replacement therapy 12.L Introduction 12.2 The composition of int¡ave¡sss imm¡asglobulin preparations 12.2.L IgG subclass content of intravenous immuûsglobulin preparations 12.2.2 Antibody content of intravenous imrnunsglsþr'lin preparations 12.3 IgG subclass replacement by immunsgls6rllin administration 12.3.L IgG subclass replacement in hlpoga--aglobulinaemic patients 12.3.1.1 Patient TN (IgA and IgG deficiency) 12.3.L.2 Patient BN (IgG deficiency) PAGE NO. 12-3.L.3 Patient SL (IgA and IgG deficiency) ?32 12.3.1.4 Patient MW (Ie¡A" IgG and IgM deficienry) ?s L2.32 IgG subclass replacement i.n IgG subclass-deficient patients ?37 ]-2.3.2.L Patieut JB 231 72.3.2.2 Patient RL 243 72.3.2.3 Patient BH u4 123.2.4 Patient AW 2A6 12.4 gumm¿¡y 250 CIIAPTER üt - IgG subclass concentrations in saliva and crcrebrospinat lluid 252 13.r Introduction 253 1i.2 Results 253 1i.2.L IgG subclasses in saliva 253 132.2 IgG subclasses in cerebrospinal fluid 254 ÍÌ3 glmm¿¡y ?55 CHAPTER 14 - Discussiou, concrusions and Recommendations ?Á2 L4.T Discussion incorporating - IgG subclass quantitation 2.63 - IgA and IgG subdass deficiency 2ß4 - IgG4 deficiency and infection proneoess ?Á8 - possible -":!T^-. of infection proneness h IgG4 deficiency 270 - treatment of IgG subclass deficiencies n4 n5 276 218 28t L4.2 Conclusions 2U L43 Recotttmendations ?35 Bibliography 287 Publications 311 B TIIESIS STJMMARY Athougb tle existence of fou¡ isotypes of IgG, known as IgG subclasses, has been recognised for over 20 years, there is still a great deal of confusion about both the definition and the significance of abnormal IgG subclass concentrations. This is partly because accurate measurement of the IgG subclasses is <lifficult and results have often been un¡eliable. Accu¡ate normal rânges for patients of different ages have, therefore, been difficult to establish. Studies of patients with subclass abnormalities have been largely anccdotal. It has, however, been suggested that IgG subclass deficiencies may prove to be the most common form of primary immr¡rsdeficiency. In many children who suffer recurrent infections, standa¡d immuno function studies including mcasurcmcnts of IgA, IgG and IgM, neutrophil and þmphocytc function studics and serum complement sç¡esning fails to detect a particular immunological problem. Some investþators have suggested that an IgG subclass deficiency may exist in a considerable proportion of tlese patients and may be associated with impaired production of antibodies to a variety of antigens. Other studies suggest that IgG subclass deficiency may not be an important factor. The chief aim of this project was to help to clarify ss6e sf rhis confusion by developing a reliable enzyme-linked immunosorbent assay (ELISA) technique and using this to a) establish percentile ranges for IgG subclasses in healthyAust¡alian children. b) quantitate serum IgG subclasses in groups of patients with differing types and degrees of infection proneness. Ð quantitate serially serum IgG subclasses in child¡en with immuuodeficiency states who a¡e receiving regular immr¡rsglsþrrlin infusions. These studies have increased ou¡ understandi"g of the relationship between IgG subclass deficiencies and infection pronenoss in children, and have resulted in suggestions for directions for fu¡ther work in this a¡ea. The ELISA technique was developed using monoclonal antibodies to each of the IgG subclasses. 9 Serum samples from healthy Aust¡alian children were used to determine age-related percentfe rånges for IgG subclasses. Previous studies have generally used less sensitive assay techniques and have not been able to define tle lower limit of normal for IgG4 which is found in relatively low concentrations in many normal sera.
Load more

Recommended publications
  • IDF Patient & Family Handbook
    Immune Deficiency Foundation Patient & Family Handbook for Primary Immunodeficiency Diseases This book contains general medical information which cannot be applied safely to any individual case. Medical knowledge and practice can change rapidly. Therefore, this book should not be used as a substitute for professional medical advice. FIFTH EDITION COPYRIGHT 1987, 1993, 2001, 2007, 2013 IMMUNE DEFICIENCY FOUNDATION Copyright 2013 by Immune Deficiency Foundation, USA. REPRINT 2015 Readers may redistribute this article to other individuals for non-commercial use, provided that the text, html codes, and this notice remain intact and unaltered in any way. The Immune Deficiency Foundation Patient & Family Handbook may not be resold, reprinted or redistributed for compensation of any kind without prior written permission from the Immune Deficiency Foundation. If you have any questions about permission, please contact: Immune Deficiency Foundation, 110 West Road, Suite 300, Towson, MD 21204, USA; or by telephone at 800-296-4433. Immune Deficiency Foundation Patient & Family Handbook for Primary Immunodeficency Diseases 5th Edition This publication has been made possible through a generous grant from Baxalta Incorporated Immune Deficiency Foundation 110 West Road, Suite 300 Towson, MD 21204 800-296-4433 www.primaryimmune.org [email protected] EDITORS R. Michael Blaese, MD, Executive Editor Francisco A. Bonilla, MD, PhD Immune Deficiency Foundation Boston Children’s Hospital Towson, MD Boston, MA E. Richard Stiehm, MD M. Elizabeth Younger, CPNP, PhD University of California Los Angeles Johns Hopkins Los Angeles, CA Baltimore, MD CONTRIBUTORS Mark Ballow, MD Joseph Bellanti, MD R. Michael Blaese, MD William Blouin, MSN, ARNP, CPNP State University of New York Georgetown University Hospital Immune Deficiency Foundation Miami Children’s Hospital Buffalo, NY Washington, DC Towson, MD Miami, FL Francisco A.
    [Show full text]
  • CDG and Immune Response: from Bedside to Bench and Back Authors
    CDG and immune response: From bedside to bench and back 1,2,3 1,2,3,* 2,3 1,2 Authors: Carlota Pascoal , Rita Francisco , Tiago Ferro , Vanessa dos Reis Ferreira , Jaak Jaeken2,4, Paula A. Videira1,2,3 *The authors equally contributed to this work. 1 Portuguese Association for CDG, Lisboa, Portugal 2 CDG & Allies – Professionals and Patient Associations International Network (CDG & Allies – PPAIN), Caparica, Portugal 3 UCIBIO, Departamento Ciências da Vida, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal 4 Center for Metabolic Diseases, UZ and KU Leuven, Leuven, Belgium Word count: 7478 Number of figures: 2 Number of tables: 3 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jimd.12126 This article is protected by copyright. All rights reserved. Abstract Glycosylation is an essential biological process that adds structural and functional diversity to cells and molecules, participating in physiological processes such as immunity. The immune response is driven and modulated by protein-attached glycans that mediate cell-cell interactions, pathogen recognition and cell activation. Therefore, abnormal glycosylation can be associated with deranged immune responses. Within human diseases presenting immunological defects are Congenital Disorders of Glycosylation (CDG), a family of around 130 rare and complex genetic diseases. In this review, we have identified 23 CDG with immunological involvement, characterised by an increased propensity to – often life-threatening – infection.
    [Show full text]
  • Patient & Family Handbook
    Immune Deficiency Foundation Patient & Family Handbook For Primary Immunodeficiency Diseases This book contains general medical information which cannot be applied safely to any individual case. Medical knowledge and practice can change rapidly. Therefore, this book should not be used as a substitute for professional medical advice. SIXTH EDITION COPYRIGHT 1987, 1993, 2001, 2007, 2013, 2019 IMMUNE DEFICIENCY FOUNDATION Copyright 2019 by Immune Deficiency Foundation, USA. Readers may redistribute this article to other individuals for non-commercial use, provided that the text, html codes, and this notice remain intact and unaltered in any way. The Immune Deficiency Foundation Patient & Family Handbook may not be resold, reprinted or redistributed for compensation of any kind without prior written permission from the Immune Deficiency Foundation. If you have any questions about permission, please contact: Immune Deficiency Foundation, 110 West Road, Suite 300, Towson, MD 21204, USA; or by telephone at 800-296-4433. Immune Deficiency Foundation Patient & Family Handbook For Primary Immunodeficiency Diseases 6th Edition The development of this publication was supported by Shire, now Takeda. 110 West Road, Suite 300 Towson, MD 21204 800.296.4433 www.primaryimmune.org [email protected] Editors Mark Ballow, MD Jennifer Heimall, MD Elena Perez, MD, PhD M. Elizabeth Younger, Executive Editor Children’s Hospital of Philadelphia Allergy Associates of the CRNP, PhD University of South Florida Palm Beaches Johns Hopkins University Jennifer Leiding,
    [Show full text]
  • Assessment of the Humoral Immune System in Adults with Respiratory Tract Disease
    Assessment of the humoral immune system in adults with respiratory tract disease Diana van Kessel Assesment of the humoral immune system in adults with respiratory tract disease D.A. van Kessel Thesis University Utrecht, the Netherlands ISBN: 978-94-90329-35-8 NUR: 870 Cover illustration: Henk ten Have, Zoelen, the Netherlands Cover design and lay-out: emjee | grafische vormgeving, Varik, the Netherlands Print: Veldhuis Media BV, Raalte, the Netherlands © 2017, D.A. van Kessel All rights are reserved. No part of this publication may be reproduced without written permission of the author. The copyright of articles that already have been published has been transferred to the respective journals. Assessment of the humoral immune system in adults with respiratory tract disease Evaluatie van het humorale afweersysteem bij volwassenen met een aandoening van de ademhalingswegen (met een samenvatting in het Nederlands) Proefschrift ter verdediging van de graad van doctor aan de Universiteit Utrecht op gezag van de rector magnificus, prof. dr. G.J. van der Zwaan, ingevolge het besluit van het college voor promoties in het openbaar te verdedigen op dinsdag 7 november 2017 des middags te 12.45 uur door Dirkje Anna van Kessel geboren op 13 december 1955 te Culemborg Promotoren: Prof.dr. J.C. Grutters Prof.dr. G.T. Rijkers Copromotor: Dr. P. Zanen Paranimfen: Thijs Hoffman Joost Jacobs Dedicated to Frans Jozef†, Isabelle en Joost Jacobs Table of contents Chapter 1: General introduction, aims and outline of the thesis 3 Part I: Immunological screening
    [Show full text]
  • Clinical and Immunological Features of 78 Adult Patients with Primary Selective Igg Subclass Defciencies
    Archivum Immunologiae et Therapiae Experimentalis (2019) 67:325–334 https://doi.org/10.1007/s00005-019-00556-3 ORIGINAL ARTICLE Clinical and Immunological Features of 78 Adult Patients with Primary Selective IgG Subclass Defciencies Amrita Khokar1,3 · Sudhir Gupta1,2 Received: 13 January 2019 / Accepted: 23 July 2019 / Published online: 30 July 2019 © L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019 Abstract The purpose of this study is to describe both clinical and immunological features in large cohort of adult patients with IgG subclass defciency, and response to immunoglobulin therapy. This is a retrospective study of data obtained from electronic medical records and paper charts of 78 patients with IgG subclass defciency seen and followed at our immunology clinics from 2010 to 2016. Both isolated selective IgG subclass defciency as well as combined (two) subclass defciencies were observed. IgG3 subclass defciency, isolated and in combination with other IgG subclass defciency, is the most frequent of IgG subclass defciency. A majority of patients presented with upper and lower respiratory tract infections, especially chronic sinusitis. Both allergic and autoimmune manifestations are common; however, there is no subclass preference. The propor- tions and absolute numbers of CD3 + T cells, CD4 + T and CD8+ T cells, CD19 + B cells, and CD3−CD16+CD56+ NK cells were normal in the majority of patients in all IgG subclass defciencies. Total serum IgG levels did not correlate with IgG subclass levels across all IgG subclass defciencies. Anti-pneumococcal polysaccharide antibody responses were impaired in 56% of patients. IgG3 subclass defciency is the most common IgG subclass defciency, and anti-polysaccharide antibody responses are distributed among IgG subclasses with modest preference in IgG2 subclass.
    [Show full text]
  • Immunological Disturbances in the Pathogenesis of Malabsorption
    J Clin Pathol: first published as 10.1136/jcp.s3-5.1.146 on 1 January 1971. Downloaded from J. clin. Path., 24, Suppl. (Roy. Coll. Path.), 5, 146-150 Immunological disturbances in the pathogenesis of malabsorption J. R. HOBBS From the Department of Chemical Pathology, Westminster Medical School, London Before considering the pathogenesis of malabsorp- First, while still susceptible to acid and pepsin tion, I will briefly review the known immune mech- in the gastric juice, the secretory IgA added there- anisms of the normal gut. The post hoc effects that after is largely resistant to normal intestinal pH and malabsorption can have upon immunity must also enzymes, so that it can persist through to the faeces. be mentioned, so that at the time a patient presents This accounts for polio virus coproantibody (Kono, and is investigated these will not be confused with Ikawa, Yaoi, Hamada, Ashihara, and Kawamaki, true propter hoc effects immunological disturbances 1966), conclusively shown to be IgA by Berger, can have on malabsorption. Ainbender, Hodes, Zepp, and Hevizy (1967). Secondly, secretory IgA can fix complement The Normal Immune Defence of the Gut (Adinolfi, Glynn, Lindsay, and Milne, 1966) and can thereby cause holes to form in the lipid mem- Normal immune mechanisms involve humoral and branes of microorganisms. In the case of Gram- cellular components and for the gut more is known negative bacteria, which have an underlying poly- of the former. saccharide backbone, lysozyme (also present in the In 1922, Davies showed that antibodies against secretions) can enter through such holes in the lipidcopyright.
    [Show full text]
  • Immunoglobulin G Subclass Deficiencies in Adult Patients with Chronic Airway Diseases
    ORIGINAL ARTICLE Immunology, Allergic Disorders & Rheumatology http://dx.doi.org/10.3346/jkms.2016.31.10.1560 • J Korean Med Sci 2016; 31: 1560-1565 Immunoglobulin G Subclass Deficiencies in Adult Patients with Chronic Airway Diseases Joo-Hee Kim,1 Sunghoon Park,1 Immunoglobulin G subclass deficiency (IgGSCD) is a relatively common primary Yong Il Hwang,1 Seung Hun Jang,1 immunodeficiency disease (PI) in adults. The biological significance of IgGSCD in patients Ki-Suck Jung,1 Yun Su Sim,1 with chronic airway diseases is controversial. We conducted a retrospective study to Cheol-Hong Kim,1 Changhwan Kim,2 characterize the clinical features of IgGSCD in this population. This study examined the 1 and Dong-Gyu Kim medical charts from 59 adult patients with IgGSCD who had bronchial asthma or chronic obstructive pulmonary disease (COPD) from January 2007 to December 2012. Subjects 1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Hallym were classified according to the 10 warning signs developed by the Jeffrey Modell University Medical Center, Anyang, Korea; 2Division Foundation (JMF) and divided into two patient groups: group I (n = 17) met ≥ two JMF of Pulmonary and Allergy, Department of Medicine, criteria, whereas group II (n = 42) met none. IgG3 deficiency was the most common Jeju National University Hospital, Jeju, Korea subclass deficiency (88.1%), followed by IgG4 (15.3%). The most common infectious Received: 12 February 2016 complication was pneumonia, followed by recurrent bronchitis, and rhinosinusitis. The Accepted: 12 June 2016 numbers of infections, hospitalizations, and exacerbations of asthma or COPD per year were significantly higher in group I than in group II (P < 0.001, P = 0.012, and P < 0.001, Address for Correspondence: respectively).
    [Show full text]
  • Treatment of Selective Iga Deficiency
    Immune Deficiency Foundation Patient & Family Handbook for Primary Immunodeficiency Diseases Australasian Edition This book contains general medical information which cannot be applied safely to any individual case. Medical knowledge and practice can change rapidly. Therefore, this book should not be used as a substitute for professional medical advice. Australasian Edition COPYRIGHT 1987, 1993, 2001, 2007, 2013 IMMUNE DEFICIENCY FOUNDATION Copyright 2013 by Immune Deficiency Foundation, USA. Readers may redistribute this article to other individuals for non-commercial use, provided that the text, html codes, and this notice remain intact and unaltered in any way. The Immune Deficiency Foundation Patient & Family Handbook may not be resold, reprinted or redistributed for compensation of any kind without prior written permission from the Immune Deficiency Foundation. If you have any questions about permission, please contact: Immune Deficiency Foundation, 110 West Road, Suite 300, Towson, MD 21204, USA; or by telephone at 800-296-4433. Immune Deficiency Foundation Patient & Family Handbook for Primary Immunodeficency Diseases Australasian Edition The printing of the Australasian Edition was made possible by Immune Deficiencies Foundation Australia (IDFA) PO Box 969 Penrith NSW 2751 www.idfa.org.au [email protected] Immune Deficiency Foundation 110 West Road, Suite 300 Towson, MD 21204 800-296-4433 www.primaryimmune.org [email protected] EDITORS R. Michael Blaese, MD, Executive Editor Francisco A. Bonilla, MD, PhD Immune Deficiency Foundation Boston Children’s Hospital Towson, MD Boston, MA E. Richard Stiehm, MD M. Elizabeth Younger, CPNP, PhD University of California Los Angeles Johns Hopkins Los Angeles, CA Baltimore, MD CONTRIBUTORS Mark Ballow, MD Joseph Bellanti, MD R.
    [Show full text]
  • Chapter 11 Hyper Igm Syndromes
    Hyper IgM Syndromes Chapter 11 Hyper IgM Syndromes Patients with Hyper-IgM (HIGM) syndrome are susceptible to recurrent and severe infections and in some types of HIGM syndrome opportunistic infections and an increased risk of cancer as well. The disease is characterized by decreased levels of immunoglobulin G (IgG) in the blood and normal or elevated levels of IgM. A number of different genetic defects can cause HIGM syndrome. The most common form is inherited as an X-chromosome linked. Most of the other forms are inherited as autosomal recessive traits and therefore can affect both boys and girls. Definition of Hyper IgM Syndromes Patients with HIGM syndrome have an inability to switch immunity and are also susceptible to all kinds of from the production of antibodies of the IgM type to infections, particularly opportunistic infections and to antibodies of the IgG, IgA or IgE types. As a result, some types of cancer. patients with this disease have decreased levels of IgG Other forms of HIGM syndrome are inherited as and IgA but normal or elevated levels of IgM in their autosomal recessive traits and have been observed in blood. These different types of antibodies perform both girls and boys. (See chapter titled “Inheritance.”) different functions and are all important in fighting One of these forms results from a defect in CD40 and is infections. Normally, B-lymphocytes can produce IgM clinically identical to XHIGM (the disease with the defect antibodies on their own, but they require interactive help in CD40 ligand). Other autosomal recessive forms of from T-lymphocytes in order to switch from IgM to IgG, HIGM syndrome result from defects in genes that are IgA or IgE.
    [Show full text]
  • Does the Hyper Igm Phenotype Affect Prognosis in Ataxia Telangiectasia?
    ASTHMA doi: 10.21911/aai.523 ALLERGY IMMUNOLOGY Asthma Allergy Immunol 2020;18:38-46 ASTIM ALLERJİ İMMÜNOLOJİ RESEARCH ARTICLE Received: 08.03.2020 • Accepted: 26.03.2020 Online Published: 06/04/2020 Does the Hyper IgM Phenotype Affect Prognosis in Ataxia Telangiectasia? Zehra Şule HASKOLOĞLU1 , Caner AYTEKIN2 , Sevgi KÖSTEL BAL1 , Candan ISLAMOĞLU1 , Kübra BASKIN1 , Zeynep YAVUZ3 , Demet ALTUN4 , Serdar CEYLANER5 , Figen DOĞU1 , Aydan IKINCIOĞULLARI1 1 Department of Pediatric Immunology and Allergy, Ankara University School of Medicine, Ankara, Turkey 2 Department of Pediatric Immunology, University of Health Sciences, Ankara Sami Ulus Maternity, Child Health and Diseases Training and Research Hospital, Ankara, Turkey 3 Department of Biostatistics, Ankara University School of Medicine, Ankara, Turkey 4 Department of Pediatrics, Ufuk University School of Medicine, Ankara, Turkey 5 Intergen Genetics Diagnosis Center, Ankara, Turkey Corresponding Author: Zehra Şule HASKOLOĞLU * [email protected] ABSTRACT Objective: To evaluate the characteristics of the patients who were followed-up with the diagnosis of ataxia telangiectasia (AT) and to assess the relationship between the hyper IgM (HIGM) phenotype and their prognosis. Materials and Methods: From 2007 to 2019, the study included 68 patients aged 3-35 years who were followed-up with the diagnosis of AT. We retrospectively evaluated the clinical and immunological characteristics and follow-up results. Results: There were 36 girls and 32 boys with a median follow-up of 10 years (1-12 years). The most common complaints upon admission were unsteady walk in 87%, infection in 6%, presence of a family history in 6%, and intracranial mass in 1%. The marriage was consanguineous in 85% of the parents.
    [Show full text]
  • Intravenous Immune Globulins (Flebogamma DIF, Gammagard Liquid, Gammagard S/D, Gammaked, Gammaplex, Gamunex-C, Octagam, Panzyga, Privigen)
    Intravenous Immune Globulins (Flebogamma DIF, Gammagard Liquid, Gammagard S/D, Gammaked, Gammaplex, Gamunex-C, Octagam, Panzyga, Privigen) When requesting Intravenous Immune Globulins (Flebogamma DIF, Gammagard Liquid, Gammagard S/D, Gammaked, Gammaplex, Gamunex-C, Octagam, Panzyga, Privigen), the individual requiring treatment must be diagnosed with an FDA-approved indication or an approved off-label compendial use and meet the specific coverage guidelines and applicable safety criteria for the covered indication. FDA-Approved Indications Intravenous Immune globulin (IVIG) injection is indicated for the treatment of: • Primary humoral immunodeficiency including but not limited to, congenital agammaglobulinemia, common variable immunodeficiency, x-linked agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies. • Idiopathic thrombocytopenia purpura (ITP) to raise platelet counts to prevent bleeding or to allow a patient with ITP to undergo surgery • Chronic inflammatory demyelinating polyneuropathy (CIDP) to improve neuromuscular disability and impairment and for maintenance therapy to prevent relapse • Multifocal motor neuropathy (MMN) to improve muscle strength and disability • Prevention of bacterial infections in hypogammaglobulinemia and/or recurrent bacterial infections associated with B-cell chronic lymphocytic leukemia • Prevention of coronary artery aneurysms associated with Kawasaki syndrome Approved Off-Label Compendial Uses • Secondary humoral immunodeficiency • Antibody-mediated rejection in solid
    [Show full text]
  • Making a Diagnosis of Common Variable Immunodeficiency: a Review
    Open Access Review Article DOI: 10.7759/cureus.6711 Making a Diagnosis of Common Variable Immunodeficiency: A Review Asma Ghafoor 1 , Shona M. Joseph 1 1. Allergy and Immunology, Nova Southeastern University School of Osteopathic Medicine, Davie, USA Corresponding author: Asma Ghafoor, [email protected] Abstract Common variable immunodeficiency (CVID) is a condition that inhibits the function of the immune system, making those with the condition more susceptible to infection from external pathogens, including bacteria and, less often, viruses. The immune disorder is marked by low immunoglobulin levels of immunoglobulin G (IgG) and IgA as well as IgM in some patients. These immune abnormalities typically result in recurrent sinopulmonary infections and can result in serious complications such as pneumonia and chronic lung disease. Other manifestations include poor vaccine response and defective antibodies in a patient’s immune system. The disorder affects approximately one in 25,000 to one in 50,000 individuals worldwide, with the condition varying across different populations. While the underlying mechanism of disease activity remains poorly understood, only 10% of cases are known to have an underlying genetic link and approximately 25% of patients also have an autoimmune disorder. CVID commonly presents in individuals in their twenties or thirties but can present at any time between childhood through adulthood, with mortality dependent on the severity of illness and frequency of recurrent infections. Potential life-threatening consequences of CVID include malignancies, enteropathy, and autoimmune manifestations. Treatment can help alleviate symptoms and prevent continued recurrent infections and serious complications. However, the lack of awareness among primary care physicians (PCPs) makes the condition difficult to diagnose and manage.
    [Show full text]