Systemic Lupus Erythematosus
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2 Josef S. Smolen Christoph C. Zielinski Systemic Lupus Erythematosus Clinical and Experimental Aspects Foreword by G. Geyer With 60 Figures and 44 Tables Springer-Verlag Berlin Heidelberg New York London Paris Tokyo
3 Univ.-Doz. Dr. Josef S. Smolen Univ.-Doz. Dr. Christoph C. Zielinski II. Medizinische Universitatsklinik, Allgemeines Krankenhaus der Stadt Wien Garnisongasse 13, A-1090 Wien ISBN 13: e ISBN 13: DOl: / Library of Congress Cataloging in Publication Data. Systemic lupus erythematosus. Includes index. 1. Lupus erythematosus, Systemic. I. Smolen, Josef S., II. Zielinski, Christoph C., [DNLM: 1. Lupus Erythematosus, Systemic. WR 152 S9952] RC924.5.L85S ' ISBN 13: (U. S.) This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the ri9hts of translation, reprinting, re-use of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. Duplication of this publication or parts thereof is only permitted under the provisions of the German Copyright Law of September 9, 1965, in its version of June 24, 1985, and a copyright fee must always be paid. Violations fall under the prosecution act of the German Copyright Law. Springer-Verlag Berlin Heidelberg 1987 Softcover reprint of the hardcover 1st edition 1987 The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. 2127/
4 We dedicate this book to our families THE EDITORS
5 Foreword More than 140 years ago, lupus erythematosus (LE) was recognized as a disease entity by clinicians working in the field of dermatology, which had only recently become an independent medical discipline. Soon after cutaneous lupus was first reported, it was realized that, apart from the skin, the disease could involve other organs and thus be systemic in nature. The latter observations were first made by MORITZ KApOSI [1], whose work has attracted renewed attention recently and who succeeded FERDINAND VON HEBRA to the chair of dermatology at the Medical Faculty in Vienna. The early description of lupus erythematosus in both its cutaneous and systemic manifestations was thus intimately associated with Vienna and its Medical School. The next phase in the study of lupus was characterized by an increase in knowledge of the type and extent of organ involvement. The work by OSLER [2], LIBMANN and SACKS [3], and KLEMPERER [4] best represents these advances. The increase in clinical knowledge of LE finally led to DUBOIS' famous monograph [5], which was published at a time of renewed interest in SLE, elicited by the description by HARGRAVES et al. [6] of the LE-cell phenomenon. A more detailed analysis of this finding revealed that the disease was characterized by an abnormal immune response, although its pathogenetic implications were still unclear. Finally, the description of antinuclear antibodies (ANA) and, later, antibodies to double-stranded DNA indicated that these autoantibodies were universally and uniformly present in patients with LE: it thus seemed that the disease was an entity with considerable clinical variability. Later investigations into the nature and composition of ANA subsets led, however, to the conclusion that certain ANA subsets could be associated with certain clinical courses of SLE and thus be important with regard to its prognosis. Over the past two decades attention has focused upon the function of Band T cells, and the belief has prevailed that a dysfunction of either or both of these lymphocyte populations or of their subsets could be responsible for dysregulation of the immune system in LE, which would culminate in B-cell hyperactivity. The application of modem biotechnologic techniques to lupus research may lead to further enlightenment.
6 VIII Foreword Thus, current knowledge indicates that SLE represents a complex syndrome with varying clinical, immunologic and genetic characteristics. Although we have not come to a complete understanding of the etiology and pathogenesis of the disease, the area has become so complex and so many different paths have been followed that it seemed justified to suggest publication of a book on LE presenting the current state of knowledge of scientific and clinical aspects of the disease. I would like to congratulate the editors and the contributors to the book on the fulfillment of this proposal in a very informative monograph. The various papers, written by some of the most knowledgeable scientists in the field, provide every physician and scientist dealing with LE with insights into modern conceptions of this interesting disorder which still represents the prototype "autoimmune disease." Let us all hope that these insights will form a basis upon which our knowledge of LE and autoimmunity in general can build, and that a further elucidation of the pathogenesis of this disease, with which we have been confronted for more than a century, will soon be forthcoming. Vienna, March 1987 GEORG GEYER Professor of Medicine and Head, 2nd Department of Medicine, University Hospital Vienna, Austria References 1. Kaposi M (1872) Arch Dermatol Syphil (Prag) 4:36 2. Holubar K (1980) Am J Dermatopathol 2: Libmann E, Sacks B (1924) Arch Int Med 33: Kiemperer P (1952) Pathology of SLE. In: Progress in Fundamental Medicine, Lea and Fibiger, Philadelphia 5. Dubois EL (1974) Lupus Erythematosus. University of Southern California Press 6. Hargraves MM, Richmond H, Morton R (1948) Proc Staff Meet Mayo Clin 23:25
7 Table of Contents Foreword VII G. GEYER Part I: General Considerations Description of Systemic Lupus Erythematosus: A Historical Perspective W. GRANINGER, J. S. SMOLEN, and C. C. ZIELINSKI Etiologic and Pathogenetic Aspects of Systemic Lupus Erythematosus: A Critical Approach... 6 W. GRANINGER, C. C. ZIELINSKI, and J. S. SMOLEN Part II: Animal Models of Systemic Lupus Erythematosus: Genetic, Viral and Immunologic Aspects Genetic Aspects of Murine Lupus M. F. SELDIN, J. D. MOUNTZ, and A. D. STEINBERG Autoimmune Disease in New Zealand Mice T. M. CHUSED, K. L. McCoy, R. B. LAL, TH. R. MALEK, E. M. BROWN, L. J. EDISON, and P. J. BAKER The NZB x SWR Model: Insights into Viral, Immunologic, and Genetic Factors S. K. DATTA Relevance of the Murine Models of Systemic Lupus Erythematosus to Human Disease C. A. LASKIN and H. R. SMITH
8 X Table of Contents Part III: Immunologic and Genetic Aspects of Human SLE The Importance of the Study of Monoclonal Antibodies 88 D. ISENBERG, Y. SHOENFELD, and R. S. SCHWARTZ ANA Subsets in Systemic Lupus Erythematosus M. REICHLIN and J. B. HARLEY Complement and Complement Deficiencies... G. TAPPEINER The Role of Lymphokines in the Pathogenesis of Systemic Lupus Erythematosus T. A. LUGER and J. S. SMOLEN Part IV: Clinical Aspects of Human SLE Clinical and Serologic Features: Incidence and Diagnostic Approach J. S. SMOLEN Immunologic Similarities and Differences Between Systemic Lupus Erythematosus and Sjogren's Syndrome 197 H. M. MOUTSOPOULOS Pathology.... W. ULRICH and G. SYRE Cutaneous Manifestations T. A. LUGER and D. BENESCH Neurological Manifestations E. MAIDA and E. HORVATITS Radiographic Features G. SEIDL The Lupus Subset Idea.... J. S. SMOLEN, A. D. STEINBERG, and T. M. CHUSED Part V: Therapeutic Aspects of SLE An Experimental Therapeutic Approach: Clinical and Immunological Aspects of Plasmapheresis C. C. ZIELINSKI Future Immunotherapeutic Possibilities in Autoimmunity N. TALAL Subject Index. 355
9 List of Contributors P. J. BAKER D. BENESCH 2nd Department of Dermatology University of Vienna AlserstraBe 4 E. M. BROWN T. M. CHUSED S. K. DATTA Department of Medicine (Hematology/Oncology Division) Cancer Research Center New England Medical Center and Tufts University School of Medicine 171 Harrison Avenue Boston, Massachusetts 02111, USA L. J. EDISON
10 XII List of Contributors G. GEYER 2nd Department of Medicine, University Hospital University of Vienna, Garnisongasse 13 w. GRANINGER 2nd Department of Medicine, University Hospital University of Vienna, Garnisongasse 13 J. B. HARLEY Arthritis and Immunology Program Oklahoma Medical Research Foundation 825 Northeast 13th Street Oklahoma City, OK 73104, USA E. HORVATITS Department of Neurology, University Hospital University of Vienna, Lazarettgasse 17 D. ISENBERG Department of Rheumatology and Rehabilitation University College Hospital, Gower Street London WC 1 E 6 AU, Great Britain R. B. LAL C. A. LASKIN Mt. Sinai Research Institute Toronto General Hospital and Mt. Sinai Hospital Toronto, Ontario, Canada T. A. LUGER 2nd Department of Dermatology, University Hospital University of Vienna, AlserstraBe 4 E. MAIDA Department of Neurology, University Hospital University of Vienna, Lazarettgasse 17
11 List of Contributors XIII T. R. MALEK K. L. McCoy J. D. MOUNTZ Cellular Immunology Section Arthritis and Rheumatism Branch Natl. Institute of Arthritis, Diabetes, Digestive and Kidney Diseases H. M. MOUTSOPOULOS Department of Medicine, Medical School University of loannina loannina, Greece M. REICHLIN Arthritis and Immunology Program Oklahoma Medical Research Foundation 825 Northeast 13th Street Oklahoma City, Oklahoma 73104, USA G. SEIDL 2nd Department of Medicine, University Hospital University of Vienna, Garnisongasse 13 M. F. SELDIN Cellular Immunology Section Arthritis and Rheumatism Branch Natl. Institute of Arthritis, Diabetes, Digestive and Kidney Diseases Y. SHOENFELD Department of Medicine 'D' Beilinson Medical Centre Petach Tikva, Israel
12 XIV List of Contributors H. R. SMITH Medical Service Boston Veterans Administration Medical Center and Arthritis Center Boston University Boston, Massachusetts, USA J. S. SMOLEN 2nd Department of Medicine, University Hospital University of Vienna, Garnisongasse 13 G. SVRE Department of Pathology, General Hospital 4040 Linz, Austria R. S. SCHWARTZ Department of Medicine (Haematology-Oncology Division) New England Medical Center, 171 Harrison Avenue Boston, Massachusetts 02111, USA. A. D. STEINBERG Cellular Immunology Section Arthritis and Rheumatism Branch Natl. Institute of Arthritis, Diabetes, Digestive and Kidney Diseases N. TALAL Department of Medicine The University of Texas Health Science Center at San Antonio San Antonio, Texas 78284, USA G. TAPPEINER 1 st Department of Dermatology, University Hospital, University of Vienna, AlserstraBe 4 w. ULRICH Institute of Pathology University of Vienna, Spitalgasse 2 C. C. ZIELINSKI 2nd Department of Medicine, University Hospital University of Vienna, Garnisongasse 13
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