DOCSLIB.ORG

Five Cases of Alpha Chain Disease

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Five Cases of Alpha Chain Disease Gut: first published as 10.1136/gut.13.12.947 on 1 December 1972. Downloaded from Gut, 1972, 13, 947-957 Five cases of alpha chain disease WILLIAM F. DOE, K. HENRY, J. R. HOBBSI, F. AVERY JONES, C. E. DENT, AND C. C. BOOTH From the Departments of Medicine and Pathology, Royal Postgraduate Medical School, Central Middlesex Hospital, and University College Hospital, London SUMMARY Five patients suffering from alpha chain disease are described. Clinically the patients presented with clubbing and the symptoms of malabsorption. There was a characteristic, pre- dominantly plasma cell infiltrate of the wall of the small intestine. Spread of the plasmacytosis beyond the small intestine to bone marrow (1), peripheral blood (1), and probably the nasopharyn- geal lymphoid tissue (1) is described. Fragments of the heavy chain of IgA (alpha chain) were found in serum (5), urine (3), jejunal fluid (2), and saliva (1). The jejunal biopsy of one patient was shown to synthesize free alpha chain in tissue culture. A new and simple immunoselection technique for the identification of free alpha chain is described. Marked clinical remissions were achieved in two patients treated with intermittent cytotoxic and steroid therapy, and in a third patient who received intermittent cytotoxic therapy and tetracycline. There is a basic structure common to all immuno- reports of alpha chain disease (Doe, Hobbs, Henry, globulin molecules. This comprises a pair of heavy and Dowling, 1970; Laroche, Seligmann, Merillon, polypeptide chains which characterize each immuno- Turpin, Marche, Cerf, Lemaigre, Forest, and Hurez, globulin class (y for IgG, a for IgA, and ,u for IgM), 1970; Roge, Druet, and Marche, 1970; Irunberry, and a pair of light chains (K or L) which is common Benallegue, Illoul, Timsit, Abbadi, Benabdallah, http://gut.bmj.com/ to all immunoglobulin classes. Reductive cleavage Boucekkine, Ould-Aoudia, and Colonna, 1970; of the immunoglobulin molecule by papain yields Zlotnick and Levy, 1971) have described a strikingly two Fab fragments each consisting of a light chain uniform clinico-pathological picture. and part of a heavy chain, and an Fc fragment com- The purpose of this paper is to describe five prising the portions of the two heavy chains which patients suffering from alpha chain disease present- carry the specific determinants characterizing each ing several new features. A simple new diagnostic immunoglobulin class. method for detecting the alpha heavy chain fragment on September 28, 2021 by guest. Protected copyright. In many lymphoid-plasmocytic disorders such as and the clinical course and response to cytotoxic multiple myeloma, abnormal plasma cells produce therapy in three of these patients will be described. an excess of a specific immunoglobulin class with free light chains or an excess of free light chains Materials and Methods alone. In 1964, a new syndrome was described in which abnormal plasma cells produced an anom- BIOPSIES alous polypeptide fragrnent, consisting of the Fc fragment of IgG (Franklin, Lowenstein, Bigelow, Peroral jejunal biopsies were taken from beyond the and Meltzer, 1964). This condition was named ligament of Treitz using a Crosby capsule. Biopsy 'heavy chain disease'. Similar disorders of immuno- tissue was processed and stained for light and globulin peptide synthesis and assembly have been electron microscopy using standard techniques. described for IgA, the condition of 'alpha chain disease' (Rambaud, Bognel, Prost, Bernier, Le PROTEIN STUDIES Quintrec, Lambling, Danon, Hurez, and Seligmann, Electrophoresis was carried out on cellulose acetate 1968) and IgM, 'mu chain disease' (Ballard, Hamil- and immunoelectrophoresis by the high-voltage ton, Marcus, and Illes, 1970). Subsequent case method of Wieme (1965). The immunoselection plate method of Radl (1970) was adapted to detect 'Present address: Department of Chemical Pathology, Westminster the presence of free alpha chain in serum. Serum Hospital, London. was electrophoresed in agar gel containing antisera Received for publication 16 October 1972. to both K and L light chains. Thus all serum proteins 947 Gut: first published as 10.1136/gut.13.12.947 on 1 December 1972. Downloaded from 948 William F. Doe, K. Henry, J. R. Hobbs, F. A very Jones, C. E. Dent, and C. C. Booth containing light chains precipitated close to the anti-L anti-light chain antisera conjugated with origin, while alpha chain fragments were free to rhodamine, using the direct staining technique. migrate. Free alpha chain was then detected using Fluorescence was viewed through a Leitz orthoplan rabbit antiserum against polyclonal human IgA. microscope. A specific rabbit antihuman secretory piece anti- serum was provided by Dr R. Thompson and a Clinical Features specific anti-lactoferrin antiserum by Professor J. Heremans. The predominant clinical features of the five patients Albumin and immunoglobulin levels were meas- are summarized in Table I. The ages of the patients ured by a radial immunodiffusion method (Hobbs, at the time of presentation ranged from 17 to 36 1970) using the standards and normal ranges years and there were four males and one female. specified. In addition the sera of the five patients Two of the patients were Pakistanis, recently arrived were tested in serial dilutions against pooled normal in England, while the remaining three, a Greek, a serum and a standard of purified polyclonal IgA. Libyan and a Persian, were investigated following Parotid secretion was collected by Curby cup, their referral to London for medical treatment. without stimulation and jejunal fluid was obtained at jejunal biopsy. A solution of equal parts of SYMPTOMS Trasylol and 10% epsilon-amino-caproic acid was Weight loss and diarrhoea suggesting steatorrhoea used to inhibit proteinases. Urine, saliva, jejunal were presenting symptoms in all five patients. In fluid, and tissue culture fluid were concentrated addition three patients complained of intermittent where necessary by ultrafiltration in collodion generalized abdominal pain (cases 3, 4, and 5), and thimbles (Sartorius) which retained substances with tetany developed on several occasions in one other mol wt greater than 5000. (case 2). In one patient (case 3) blood appeared in the saliva; peripheral oedema was a presenting TISSUE CULTURE symptom in case 4. The duration of these symptoms Fresh jejunal mucosa was incubated at 37°C in ranged from seven months (case 5) to three and a 0'25% trypsin in phosphate-buffered saline free of half years (case 4). calcium and magnesium (Dulbecco A Oxoid). Ten per cent foetal calf serum in TC 119 medium free INTERCURRENT DISEASE http://gut.bmj.com/ of L-leucine and DL- lysine (Tissue Culture Services) One patient (case 2) developed a groin abscess from containing 20 gCi of tritiated L-leucine and DL- which human tubercle bacilli were cultured. His lysine (Radiochemical Centre, Amersham) was then tuberculosis responded to chemotherapy with added to the spun cellular deposit and incubated at streptomycin, PAS, and isoniazid. A gastric ulcer 37°C in the presence of 5% CO2 in air. Following was found in case 4 while he was receiving pred- freezing, thawing, and probe sonication, the super- nisone therapy in Greece. natant fluid was tested for the presence of alpha on September 28, 2021 by guest. Protected copyright. chain material by immunoelectrophoresis and auto- FAMILY HISTORY radiography using the method of Doniach and Pelc There was no family history of gastrointestinal (1950). disease in relatives of any of the five patients. IMMUNOFLUORESCENT STUDIES PHYSICAL SIGNS Cryostat sections of fresh frozen jejunal mucosa Finger clubbing and signs of weight loss were were stained with specific antisera for IgA, IgG, and marked in four patients (cases 1, 2, 3, and 4) and in IgM conjugated with fluoroscein isothiocyanate addition peripheral oedema occurred in case 4. A (FITC) (Nordic Laboratories) and anti-K and nasopharyngeal lymphoid tissue tumour was found Case Age Sex Nationality Duration of Symptoms Signs Symptoms 1 FT 17 F Libyan 3 yr Weight loss, diarrhoea Wasting, finger clubbing 2 AH 29 M Pakistani 1* yr Weight loss, diarrhoea, tetany Wasting, finger clubbing 3 LM 30 M Pakistani 2 yr Weight loss, abdominal pain, diarrhoea, Wasting. finger clubbing, nasopharyngeal bright blood in saliva lymphoid tissue tumour 4 GS 33 M Greek 31 yr Weight loss, abdominal pain, diarrhoea, Wasting, finger clubbing, peripheral oedema oedema 5 ZY 36 M Persian 7 mth Diarrhoea, weight loss, abdominal pain Nil Table I Clinicalfeatures in five cases ofalpha chain disease Gut: first published as 10.1136/gut.13.12.947 on 1 December 1972. Downloaded from Five cases ofalpha chain disease 949 Case Haemoglobin Blood Film White Cell Count Bone Marrow Serum Iron/ Serum Folate ESR (g/I10 ml) TIBC (ng/mt) (mm at 1 hour) (Ag/lloo ml) 1 FT 11-5 Single normoblast, 7700 - - - 81 hypochromia 79 % neutrophils 2 AH 16-1 No abnormality 10600 - 1111- 4 2 78 %/, neutrophils 3 LM 13-4 Hypochromia, 8 000 Abnormal 501276 2.9 30 eosinophilia 8 % cosinophils plasma cells 4 GS IS 0 Abnormal 7 100 Normal 301- 23-41 31 plasma cells 8 5/, plasma cells S ZY 14.5 Rouleaux formation 6 500 Normal 103/215 321 95 31 % lymphocytes Normal values 110-1301 >6 250-400 Table II Haematologicalfindings at the time ofpresentation 'Receiving folic acid therapy. - = not done. TIBC = total iron-binding capacity. in case 3 but none of the five patients had lymph increase was shown to be largely caused by a massive node, liver, or spleen enlargement, nor was any increase in the intestinal isoenzyme of alkaline abdominal mass palpable. phosphatase (Doe, Thomas, and Moss, 1972). Investigations GASTROINTESTINAL STUDIES HAEMATOLOGICAL FINDINGS Absorption tests The results of haematological studies are shown in Malabsorption of fat was found in all five cases, Table II. Eosinophilia was present in case 3 and and in cases 3, 4 and 5, D xylose and vitamin B12 http://gut.bmj.com/ morphologically abnormal plasma cells with a large malabsorption was demonstrated as well (Table IV).
Load more

Recommended publications
  • Gamma Heavy Chain Disease Complicated by Pulmonary Hypertension, Which Was Successfully Treated with Lenalidomide Sho Shibata, Akiko Fukunaga
    BMJ Case Rep: first published as 10.1136/bcr-2020-236162 on 30 November 2020. Downloaded from Case report Gamma heavy chain disease complicated by pulmonary hypertension, which was successfully treated with lenalidomide Sho Shibata, Akiko Fukunaga Hematology, Tazuke Kofukai, SUMMARY with chemotherapy using the cyclophosphamide, Medical Research Institute, Heavy chain disease (HCD) is a rare B- cell proliferative vincristine and prednisone (CVP regimen), cyclo- Kitano Hospital, Osaka, Japan neoplasm that is characterised by the production of phosphamide, vincristine, doxorubicin and predni- truncated monoclonal immunoglobulin heavy chains sone (CHOP regimen), melphalan and bortezomib. Correspondence to without light chains. Gamma HCD is a subgroup of HCD. Lenalidomide, an immunomodulatory drug (IMiD), Dr Sho Shibata; ashitaharerukana21@ gmail. com A 67- year- old man was admitted to our hospital with has not yet been used in the treatment of gamma dyspnoea and lower leg oedema. Based on the results of HCD. We herein present a case of gamma HCD Accepted 2 November 2020 heart catheterisation, he was diagnosed with pulmonary complicated by pulmonary hypertension that hypertension. Laboratory tests revealed an elevated level showed a clinical response to lenalidomide. of IgG, and serum immunoelectrophoresis showed that IgG was a monoclonal gamma heavy chain without light CASE PRESENTATION chains. Finally, he was diagnosed with gamma HCD A- 67- year old man was admitted to our hospital complicated by pulmonary hypertension. Bortezomib with dyspnoea and lower leg oedema for 1 month. and dexamethasone therapy was initiated, but became He had a history of type 2 diabetes. On examina- refractory within 8 months. Therefore, the treatment was tion, his blood pressure was 163/88 mm Hg, pulse switched to lenalidomide and dexamethasone therapy, 97/min and respiratory rate 26/min with an O2 and the disease has been stably controlled for more saturation of 88% in room air, and he had spleno- than 2 years.
    [Show full text]
  • Laboratory Testing Requirements for Diagnosis and Follow-Up of Multiple Myeloma and Related Plasma Cell Dyscrasias
    Clin Chem Lab Med 2016; 54(6): 907–919 Review Maria A.V. Willrich* and Jerry A. Katzmann Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias DOI 10.1515/cclm-2015-0580 Received June 19, 2015; accepted September 15, 2015; previously Monoclonal gammopathies published online October 28, 2015 overview and categorization Abstract: Monoclonal immunoglobulins are markers of Immunoglobulins are produced by plasma cells, and plasma cell proliferative diseases and have been described clonal plasma cell proliferative diseases usually secrete as the first (and perhaps best) serological tumor marker. a monoclonal immunoglobulin (M-protein) that can The unique structure of each monoclonal protein makes be used as a serologic “tumor” marker. Because of this them highly specific for each plasma cell clone. The dif- secreted monoclonal immunoglobulin, these diseases are ficulties of using monoclonal proteins for diagnosing and also called monoclonal gammopathies. The secreted pro- monitoring multiple myeloma, however, stem from the teins can be used as a diagnostic tool for the identifica- diverse disease presentations and broad range of serum tion of the clone of plasma cells as well as a quantitative protein concentrations and molecular weights. Because of marker to follow the course of the disease and response to these challenges, no single test can confidently diagnose therapy. Unlike most serologic tumor markers, M-proteins or monitor all patients. Panels of tests have been recom- are extremely diverse. The M-proteins each have unique mended for sensitivity and efficiency. In this review we variable region sequences and the molecules may range discuss the various disease presentations and the use of from pentameric IgM (~900,000 Daltons) to monomeric various tests such as protein electrophoresis and immuno- free light chains (~24,000 Daltons).
    [Show full text]
  • Clinicopathological Study of Spectrum of Plasma Cell Dyscrasias in a Tertiary Care Centre-Retrospective Four Year Study
    Indian Journal of Pathology and Oncology 2020;7(1):158–163 Content available at: iponlinejournal.com Indian Journal of Pathology and Oncology Journal homepage: www.innovativepublication.com Original Research Article Clinicopathological study of spectrum of plasma cell dyscrasias in a tertiary care centre-retrospective four year study Sindhu Sharma1, Jyotsna Suri1,*, Bhavneet Kour1 1Dept. of Pathology, Government Medical College, Jammu, Jammu & Kashmir, India ARTICLEINFO ABSTRACT Article history: Plasma Cell Dyscrasias (PCD) by definition are represented by excessive proliferation of a single clone Received 30-08-2019 of cells producing entire immunoglobulins, immunoglobulin fragments, heavy chains or light chains. Accepted 05-09-2019 These encompass a wide range of disorders. In this study we try to discuss the clinical and pathological Available online 22-02-2020 characteristics of this rare but important group of hematological malignancies. Materials and Methods: This study was carried out in a tertiary care centre retrospectively for a period of four years. All the cases diagnosed with Plasma Cell Dyscrasias were selected. They were re-evaluated Keywords: taking into consideration clinical aspects, radiological findings and blood and bone marrow examinations. Multiple myeloma These were further categorized using Salmon Durie Staging system. Plasma cell dyscrasia Results: During this study a total of 41 cases fulfilled the diagnostic criteria of Plasma Cell Dyscrasias. Waldenstrom’s macroglobulinemia Among them 33 were newly diagnosed cases of Multiple Myeloma, 4 cases were of relapse and 4 were of Waldenstrom’s Macroglobulinemia’s. Males outnumbered females in our study. The most common complaint was anemia (seen in 90% of cases) followed by lytic bone lesions and presence of M Band on electrophoresis.
    [Show full text]
  • Waldenström Macroglobulinemia Irene M
    Waldenström Macroglobulinemia Irene M. Ghobrial, MD Thomas E. Witzig, MD* Address *Division of Hematology, Mayo Clinic, 200 First Street, Rochester, MN 55905, USA. E-mail: [email protected] Current Treatment Options in Oncology 2004, 5:239–247 Current Science Inc. ISSN 1527-2729 Copyright © 2004 by Current Science Inc. Opinion statement Waldenström macroglobulinemia (WM) is a low-grade lymphoproliferative disorder charac- terized by the presence of an immunoglobulin M monoclonal protein in the blood and monoclonal small lymphocytes and lymphoplasmacytoid cells in the marrow. The disease is uncommon and there is a lack of clear diagnostic criteria. WM is treatable but not curable and long-term survival is possible. Therefore, the treating physician needs to carefully bal- ance the risks and benefits of treatment. Treatments are aimed at relieving symptoms resulting from marrow infiltration and the hyperviscosity syndrome. Therapies available for initiation of treatment include alkylating agents, purine nucleoside analogs, and ritux- imab. Chlorambucil has been the mainstay of treatment for many years and remains useful, especially in older patients. Rituximab has become an important new therapy for this dis- ease because of its positive treatment responses, acceptable toxicity, and lack of therapy- associated myelosuppression and myelodysplasia. Currently, rituximab is being combined with chemotherapy. Other options of treatment include interferon and corticosteroids. Emerging therapies include stem cell transplantation (autologous and allogeneic) for younger patients. Currently, there are few comparative data on which to state an absolute opinion concerning the best available treatment for patients with WM. Introduction Waldenström macroglobulinemia (WM) was first described approximately 25% of cases and are not nearly as promi- by Jan Waldenström in 1944 [1] and is classified in the nent as found in non-Hodgkin lymphoma.
    [Show full text]
  • Multiple Myeloma Making Sense of the Report Forms Parameswaran
    Multiple Myeloma Making Sense of the Report Forms Parameswaran Hari Milwaukee Medical College of Wisconsin 2003 Allogeneic (Total N=7,200) Autologous (Total N=10,500) Indications for Blood and Marrow Transplantation in North America Non-Malig Dis 5,000 Other Cancer 4,500 CLL BUS05_15.ppt 4,000 Neuroblastoma 3,500 CML 3,000 MDS/Other Leuk 2,500 ALL 2,000 Hodgkin 1,500 AML Transplants NHL 1,000 500 Myeloma 0 1 Autologous & Allogeneic Objectives the disease & its natural history What is new and what is coming? Myeloma – limitations, sources of confusion Transplantation in Myeloma – Response Criteria – The MYE form – Common Queries Questions Myeloma Disease Biology Cancer of Plasma Cells Plasma Cells secrete Immune (Monoclonal) Proteins – detected in serum or urine by electrophoresis / IFE Rarely nonsecretory type New test: Serum Free lite chains Organ dysfunction – “CRAB” Plasma Cells come from B cells circulate all over produce immune globulins Memory B cell “Activated B cell” Plasma Cell Immunoglobulins Major types of Immune Globulins IgG, IgA, IgM, IgD, IgE Light Chains – Kappa or Lambda Concept of Monoclonality Malignant plasma cell – is monoclonal One plasma cell clone = only one type of Ig K or L Rare exceptions – 2 different spikes – IgG K and IgA L 2 Myeloma Plasma Cells Grow , proliferate and infiltrate Secrete – Immunoglobulins or Light chains “Create space” - dissolve bone osteolysis Immune dysfunction Deposition of light chains / amyloid – Renal Impairment , AL amyloid Epidemiology of MM >16000 newly diagnosed Median Age at diagnosis patients per year 70 yrs (>75% are 70yrs 45000 Americans living with MM or above) Remains Incurable In 2005 – 16570 new cases and 11000 deaths Median Survival from diagnosis 33 months Similar numbers from the EU Higher (almost double) incidence in Americans of African heritage.
    [Show full text]
  • The “Other” Paraproteinemias BHS Course 06/05/2017
    The “other” paraproteinemias BHS course 06/05/2017 Ph. Vlummens Ghent University Hospital Outline presentation • Solitary plasmocytoma • Cryoglobulinemia • POEMS syndrome • Heavy chain disease Solitary plasmocytoma • The presence of plasma cell proliferation in one site without evidence of systemic involvement/CRAB • Two entities: – Solitary plasmocytoma of bone – Extramedullary plasmocytoma Finsinger, Brit J Hematol, 2015 Solitary plasmocytoma • Accounts for max. 5% of all plasma cell neoplasms diagnosed annually • Incidence 0,15/100.000 patient-years (US) • Median age at diagnosis 55 – 63 years • Male/female : 62,4 vs 37,6% • Overall survival 78,4% at 5 years (SPB <> EMP) Finsinger, Brit J Hematol, 2015 SEER database 1998 - 2007 Site (total = 1691) Amount (% of total) Bone 977 (57,78) Axial skeleton 831 (49,14) Appendicular skeleton 146 (8,63) Extramedullary plasmocytoma 540 (31,93) Upper airway tract 211 (12,48) Lower airway tract 54 (3,19) GI tract 49 (2,9) Soft tissue and connective tissue 77 (4,55) CNS 49 (3,19) Lymph nodes 25 (1,48) Skin 20 (1,18) All other sites 55 (3,25) Unspecified 174 (10,29) Thumallapally, BMC Cancer, 2017 Solitary plasmocytoma : Clinical presentation Tumour consisting of sheets of atypical plasmacells Solitary plasmocytoma : Workup Kumar et al., JNCCN, 2017 Solitary plasmocytoma : Treatment Kumar et al., JNCCN, 2017 Solitary plasmocytoma : Evolution to MM • SEER database : 32,7% progressed to symptomatic MM • Difference between SBP and EMP – Finsinger et al. (2015) SBP EMP – Soutar et al. (2004) Predominant
    [Show full text]
  • POEMS Syndrome, Heavy Chain Diseases
    Osteosclerotic Myeloma (POEMS Syndrome) Osteosclerotic Myeloma (POEMS Syndrome) Synonyms Crow-Fukase syndrome Multicentric Castleman disease Takatsuki syndrome Acronym coined by Bardwick POEMS Scheinker, first report in an autopsy case (1938) Crow described two cases (1956) POEMS: Definition Plasma cell dyscrasias often associated with peripheral neuropathies 30-50% of patients with osteosclerotic myeloma have peripheral neuropathy Only 1-8% patients with classical myeloma have neuropathy (POEMS Syndrome) Osteosclerotic myeloma often associated with Polyneuropathy: sensorimotor demyelination Organomegaly: liver, spleen Endocrinopathy: diabetes mellitus, gynecomastia, testicular atrophy, impotence Monoclonal gammopathy Skin changes: hyperpigmentation, hypertrichosis POEMS Not included in acronym: Sclerotic bone lesions (multiple) Castleman disease Papilledema Pleural effusion, edema, ascites Thrombocytosis Osteosclerotic Myeloma (POEMS Syndrome) Plasma cell proliferative disorder Plasma cell infiltrate in bone marrow Thickened trabeculae Lymph nodes with angiofollicular hyperplasia (Castleman disease) Relationship to typical plasma cell myeloma not known Osteosclerotic Myeloma (POEMS Syndrome) 1-2% of plasma cell dyscrasias Adults (median age 50 years) Male-to-female ratio 1.4:1 Some association with Kaposi sarcoma and Herpes Virus 8 (HHV 8) POEMS Syndrome Clinical Presentation Only about 13% of cases with all features of POEMS Polyneuropathy Endocrine dysfunctions Lymphadenopathy Erythrocytosis (anemia rare) Thrombocytosis POEMS Syndrome
    [Show full text]
  • Two Cases of Γ-Heavy Chain Disease and a Review of the Literature
    Hindawi Case Reports in Hematology Volume 2018, Article ID 4832619, 8 pages https://doi.org/10.1155/2018/4832619 Case Report Two Cases of γ-Heavy Chain Disease and a Review of the Literature I. Ramasamy 1 and Z. Rudzki2 1Department of Biochemistry, Worcester Royal Hospital, Worcester, UK 2Heart of England NHS Trust, Birmingham, UK Correspondence should be addressed to I. Ramasamy; [email protected] Received 5 May 2018; Revised 4 July 2018; Accepted 12 July 2018; Published 12 August 2018 Academic Editor: Marie-Christine Kyrtsonis Copyright © 2018 I. Ramasamy and Z. Rudzki. +is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Gamma heavy chain disease (c-HCD) is a rare lymphoproliferative disorder characterised by the production of a truncated immunoglobulin heavy chain. Fewer than 200 cases have been reported in the literature. In some cases, c-HCD occurs with other lymphoid neoplasms. +is study reports clinical, biochemical, haematological, and histological findings in two cases of c-HCD. We describe newer biochemical diagnostic tools (HevyLite measurement, capillary electrophoresis, and immunotyping) that can aid in the characterisation of c-HCD. +e first case is an 88-year-old woman with c-HCD. +e second case is an 81-year-old woman who developed c-HCD during treatment for Waldenstrom’s macroglobulinemia. In the second patient, histopathology identified a separate clone responsible for the secretion of the gamma heavy chain. Studies on the clonal evolution of the disease may provide insight into therapeutic implications and the genomic complexity of the disease.
    [Show full text]
  • Alpha-Chain Disease and Related Small-Intestinal Lymphoma: a Memorandum *
    Alpha-chain disease and related small-intestinal lymphoma: a Memorandum * Primary intestinal lymphotias are remarkably frequent in the Mediterranean region and South-West Asia. They are usually found in young persons from. the lower socio- economic strata of the population. These conditions sometimes present a premalignant phase characterized by plasmacytic infiltration of the small intestine. It has been reported that early treatment of cases with antibiotics is followed by complete remission, suggesting that some environmental factors may be responsible for the disease. Some patients have an abnormal alpha-chain protein in their serum. This Memorandum reviews the present knowledge of the clinical, immunological, epidemiological, and therapeutic aspects of this condition. Primary intestinal lymphomas are remarkably pre- lymphoma in man. Uniquely, the association of a valent in the Mediterranean region and South-West disordered immune response and the development Asia (1, 12, 26) and have a number of characteristic of immunoblastic sarcoma, possibly from the same features. They are most frequent in young patients clone of cells, can be studied in a cell population from underprivileged backgrounds who present with that synthesizes a distinctive marker protein. a malabsorption syndrome resulting from extensive Over the last decade data have accumulated from and diffuse infiltration of the wall of the small intes- isolated case studies in diverse regions and the time tine, predominantly by plasma cells. Clinical studies now seems opportune to initiate a new phase of suggest evolution from a premalignant cellular infil- research into this condition. As a first step, a co- trate to frank neoplasia involving more primitive ordinated international collaborative effort is essen- immunoblasts.
    [Show full text]
  • REALLY ESSENTIAL MEDICAL IMMUNOLOGY Arthur Rabson, Ivan M.Roitt, Peter J
    REALLY ESSENTIAL MEDICAL IMMUNOLOGY Arthur Rabson, Ivan M.Roitt, Peter J. Delves SECOND EDITION SECOND EDITION Really Essential Medical Immunology Arthur Rabson MB, BCh, FRCPath Department of Pathology Tufts University School of Medicine Boston USA Ivan M. Roitt DSc, HonFRCP, FRCPath, FRS Department of Immunology & Molecular Pathology Royal Free & University College Medical School London UK Peter J. Delves PhD Department of Immunology & Molecular Pathology Royal Free & University College Medical School London UK © 2005 A. Rabson, I.M. Roitt, P.J. Delves Published by Blackwell Publishing Ltd Blackwell Publishing, Inc., 350 Main Street, Malden, Massachusetts 02148-5020, USA Blackwell Publishing Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UK Blackwell Publishing Asia Pty Ltd, 550 Swanston Street, Carlton, Victoria 3053, Australia The right of the Authors to be identified as the Authors of this Work has been asserted in accordance with the Copyright, Designs and Patents Act 1988. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher. First published 2000 Reprinted 2001 Second edition 2005 Library of Congress Cataloging-in-Publication Data Rabson, Arthur. Really essential medical immunology / Arthur Rabson, Ivan M. Roitt, Peter J. Delves.— 2nd ed. p. ; cm. Rev. ed. of: Really essential medical immunology / Ivan Roitt and Arthur Rabson. 2000. Includes bibliographical references and index. ISBN 1-4051-2115-7 1. Clinical immunology. [DNLM: 1. Immunity. QW 540 R116r 2005] I.
    [Show full text]
  • Extramedullary Plasmacytoma of the Thyroid Gland Producing Gamma Heavy Chain
    Endocrinol. Japon. 1985, 32 (3), 427-433 Extramedullary Plasmacytoma of the Thyroid Gland Producing Gamma Heavy Chain SUNAO MATSUBAYASHI, HAJIME TAMAI, TOSHIMITSU SUZUKI*, Fumio MATSUZUKA**, AKIRA MIYAUCHI**, NOBUYUKI KOBAYASHI, SHUJI FUKATA, KANJI KUMA**, NOBORU YANAIHARA***, AND SHIGENOBU NAGATAKI**** Department of Psychosomatic Medicine, Kyushu University School of Medicine, Fukuoka 812. *Deprtment of Pathology, Niigata University School of Medicine, Niigata 951. **Department of Surgery, Kuma Hospital, Kobe 650. ***Laboratory of Bioorganic Chemistry, Shizuoka College of Pharmacy, Shizu- oka 422. ****Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852. Abstract We encountered a 65-year-old man with gamma heavy chain disease asso- ciated with extramedullary plasmacytoma of the thyroid gland. Serum electro- phoresis revealed an abnormal fast gamma band that cross-reacted with anti- IgG (FcƒÁ) sera immunoelectrophoretically. Intracytoplasmic monoclonal immunoglobulin, IgG (FcƒÁ), was demonstrated in thyroid tissue sections using an indirect immunofluorescence method. After surgery, the serum abnormal fast gamma band disappeared. At the time of writing, the patient has survived 18 months post-surgery. Gamma heavy chain disease is regarded only after exclusion of skeletal myeloma on as a lymphoproliferative disorder charac- a long-term follow-up. Recently, Seligmann terized by the heavy chain fragment of IgG. et al. (1979) and Kyle et al. (1981) reported About 60 patients with this disorder have gamma heavy chain disease associated with been described since the first report by plasmacytoma of the thyroid gland, but not Franklin et al. (1964). Its course is usually in detail. fatal (Kyle et al., 1981). Extramedullary We had an opportunity to observe plasmacytoma of the thyroid gland is even another patient with gamma heavy chain rarer.
    [Show full text]
  • Gamma Heavy Chain Disease (Γ-HCD) As Iatrogenic Immunodeficiency
    lin Journal of clinical and experimental hematopathology JC Vol. 59 No.4, 196-201, 2019 EH xp ematopathol Case report Gamma heavy chain disease (γ-HCD) as iatrogenic immunodeficiency- associated lymphoproliferative disorder: Possible emergent subtype of rheumatoid arthritis-associated γ-HCD Hiroko Tsunemine,1) Yuriko Zushi,2) Miho Sasaki,2) Yuko Nishikawa,3) Akiyo Tamura,4) 1) 1) 5) 1) Yumi Aoyama, Taiichi Kodaka, Tomoo Itoh, Takayuki Takahashi Gamma heavy chain disease (γ-HCD) is a rare B-cell neoplasm that produces a truncated immunoglobulin γ-heavy chain lack- ing the light chain. The clinical features of γ-HCD are heterogeneous, resembling different types of B-cell lymphomas. Although rheumatoid arthritis (RA) is one of the common underlying diseases of γ-HCD, the therapeutic modality for RA has changed greatly in recent years; therefore, γ-HCD as iatrogenic immunodeficiency-associated lymphoproliferative disorder (LPD) should be taken into consideration. Here, we report such a γ-HCD case. A 69-year-old female was admitted because of fever, multiple lymph node swelling in the abdominal cavity, and peritoneal effusion. She had been treated using methotrexate for RA for 14 years, and using infliximab and adalimumab for Crohn’s disease for one year. The serum concentration of IgG was 3,525 mg/dL, which was revealed to be monoclonal IgG lacking the light chain by rocket immunoselection assay. CD19+/ CD20-/smκ−/smλ− large abnormal lymphocytes were observed in the peritoneal fluid, which were demonstrated to be clonal B-cells by PCR examination. Discontinuation of methotrexate did not improve her condition and she died of pneumonia.
    [Show full text]