Autoimmune Endocrinopathies

439 Pages·1999·16.495 MB·English

by  Yoshinori Iwatani MD, PhD, Mikio Watanabe MD, PhD (auth.), Robert Volpé MD, FRCP(C), FACP, FRCP (eds.)

AUTOIMMUNE
ENDOCRINOPATHIES
CONTEMPORARY ENDOCRINOLOGY
P. Michael Conn, EmroR
SERIEs
21. Hormonesand the Heart in Health and Disease, edited by LEONARD SHARE, 1999
20. Endocrino/ogy ofA ging, edited by JOHN E. M ORLEY AND LUCRETIA VAN DEN BERG, 1999
19. Human Growth Hormone: Research and Clinical Practice, edited by Rar G. SMITH
AND MICHAEL 0. THORNER, 1999
18. Menopause: Endocrinology and Management, edited by DAVID B. SEIFERAND
ELIZABETH A. KENNARD, 1999
17. The IGF System: Molecu/ar Biology, Physiology, and Clinical Applications,
edited by RoN G. RosENFELD AND CHARLES T. RoBERTS, JR., 1999
16. Neurosteroids: A New Regulatory Function in the Nervaus System, edited by
ETIENNE-EMILE BAULIEU, MICHAEL SCHUMACHER, AND PAUL ROBEL, 1999
15. Autoimmune Endocrinopathies, edited by RoBERT VoLPi:, 1999
14. Hormone Resistance Syndromes, edited by J. LARRY JAMESON, 1999
13. Hormone Replacement Therapy, edited by A. WAYNE MEIKLE, 1999
12. Insulin Resistance: The Metabolie Syndrome X edited by GERALD M. REAVEN AND
AMI LAWS, 1999
11. Endocrinology ofB reast Cancer, edited by ANDREA MANN!, 1999
10. Molecu/ar and Cellular Pediatric Endocrinology, edited by
STUART HANDWERGER, 1999
9. The Endocrinology ofPregnancy, edited by FuLLER W. BAZER, 1998
8. Gastrointestinal Endocrinology, edited by GEORGE H. GREELEY, JR., 1999
7. Clinical Management ofD iabetic Neuropathy, edited by ARISTIDIS VEvEs, 1998
6. G Proteins, Receptors, and Disease, edited by ALLEN M. SPIEGEL, 1998
5. Natriuretic Peptides in Health and Disease, edited by Wnus K. SAMSON
AND ELLIS R. LEVIN, 1997
4. Endocrinology ofCritical Disease, edited by K. PATRICK OBER, 1997
3. Diseases ofthe Pituitary: Diagnosis and Treatment, edited by
MARGARET E. W!ERMAN, 1997
2. Diseases ofthe Thyroid, edited by LEWIS E. BRAVERMAN, 1997
1. Endocrinology ofthe Vasculature, edited by JAMES R. SowERS, 1996
AuTOIMMUNE
ENDOCRINOPATHIES
Edited by
RoBERT VoLPE,
MD
University ofToronto, Toronto, Ontario,
Canada
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
© 1999 Springer Science+Business Media New York
Originally published by Hurnana Press Inc. in 1999
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Cover caption: Photomicrograph of thyroid showing Hashimoto's ( autoimmune) thyroiditis.
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Autoimmune endocrinopathies I edited by Robert Volpe.
p. cm. - (Contemporary endocrinology; 15)
Includes bibliographical references and index.
ISBN 978-1-4757-4572-6 ISBN 978-1-59259-704-8 (eBook)
DOI 10.1007/978-1-59259-704-8
I. Endocrine glands-Diseases-Immunological aspects.
2. Autoimmune diseases. I. Volpe, Robert, 1926- . II. Series:
Contemporary endocrinology ; 15.
RC649.A976 1999
616.4' 079--dc21
99-10951
CIP
PREFACE
This preface introduces Autoimmune Endocrinopathies, a series of essays on these
pathologies and related topics written by experts in the field. This is the fourth volume
on this general subject that I have written (1) or edited (2, 3) over 18 years, and given my
advanced age, this is undoubtedly the last. Having read the chapters offered by the
contributors to the present volume, I hope it will not be unseemly ifl make the claim that
this last effort is also the best.
Although there are diverse features that distinguish these autoimmune endocrinopa
thies, there are also certain links of susceptibility and pathogenesis that connect them.
Chapters in this volume will attest to the view that the disturbance( s) in immunoregulation
that lead to the organ-specific autoimmune endocrine diseases appear tobe partly genetic
and partly environmental in nature. Autoimmune endocrine diseases (and those
nonendocrine autoimmune disorders with which they are associated) (Table 1) tend to
aggregate in families, and more than one of these maladies may occur concomitantly
within the same patient or her/his family. The modes of inheritance ofthese disorders do
not follow simple genetic rules, and such environmental factors as stress, infection,
trauma, drugs, nutrition, smoking, and aging may distort the penetrance and expressivity
of these conditions (by their actions on the immune system). Questions related to the
pathogenesis and immunogenetics ofthe autoimmune endocrinopathies are largely dealt
with in Chapters 1-5, and are also discussed in relation to the specific entities in the
chapters that follow. There tends tobe a strong female preponderance in most ofthese
autoimmune diseases that appears tobe largely related to hormonal factors, as described
in Chapter 7, on sex hormones and autoimmunity. Additionally, as the nature of the
autoantigens involved in these diseases became increasingly known (see Chap. 8,
Autoantigens in the Autoimmune Endocrinopathies), it became clear that the antigen(s)
in each ofthe entities are distinct from one another, and thus antigenic cross-reactivity
was not likely to explain the occasional association of more than one organ-specific
autoimmune disease in the same individual; rather, the explanation may lie in closely
related genetically induced disturbances in the immune system. The proliferative response
of subsets ofT lymphocytes to the different autoantigens has been shown tobe antigen
( disease )-specific. Finally, in experimental animals, the inheritance ofinsulin-dependent
diabetes mellitus can be shown tobe separate from that of autoimmune thyroid disease.
One thus can only conclude that the autoimmune endocrine diseases are each based on
unrelated antigens, and are genetically separate, despite overlapping genetic links. The
essays on each of the specific conditions in turn are followed by a chapter on possible
preventive measures, as weil as new immunomodulatory approaches (Chap. 17).
Certainly, there is much tobe learned about the events that Iead to the development and
progression, as well as the treatment and possible prevention, of these disorders. A
number of questions remain unanswered, and form the grist for future studies. F or example,
the precise genes for each organ-specific autoimmune disease need to be identified and
a comparison made between the various entities. Once identified, their actions and inter
actions will have tobe worked out. The antigen-presenting genes are prime suspects for
V
VI Preface
Table 1
Associated Endocrine and Nonendocrine Organ-Specific Autoimmune Disease
Endocrinopathy N onendocrine disease
Hashimoto' s thyroiditis (a nd variants) Pemicious anemia
Graves' (Parry's, Basedow's) disease Myasthenia gravis
Insulin-dependent diabetes mellitus Vitiligo
Autoimmune Addison's disease Sjögren's syndrome
Autoimmune oophoritis and orchitis Rheumatoid arthritis
Autoimmune hypoparathyroidism Idiopathic thrombocytopenic purpura
Autoimmune hypophysitis Disseminated Iupus erythematosus
Infertility due to antisperm antiborlies Chronic active hepatitis
Malabsorption syndrome
Primary biliary cirrhosis
this role, but this remains tobe proved. Ifs o, what is the nature ofthe genetic abnormality?
Do autoantigens constantly have access to, and activate elements ofthe immune system,
such as regulatory cells, in normal individuals? Can a genetic abnormality in antigen
presenting cells be modified by cytokines or other means? What is the role ofthe target
cell: Is it a passive victim to immunological events? Do mutations of autoantigens, e.g.,
surface receptors, play any role in inducing autoimmunity? Is there a role for microbes
and their antigens in the induction of endocrine autoimmunity? What role, if any, does
molecular mimicry play? Though there is no compelling evidence for this notion at
present, some workers feel that such a possibility is at least attractive. If there is such a
role, can it be modified? What is the nature ofthe variations of antigenic epitope binding
by antiborlies and T lymphocytes? Arethese ofg enetic or clinical significance? What role
do environmental influences have in inducing endocrine autoimmunity? Which environ
mental influences? Do these all play on the immune system? If so, where and how? How
are cytokines coordinated, by what mechanisms, and what are their roles? What are the
roles ofo ther ancillary molecules, e.g., ICAM-1, LF A, HSP, CD40, Ctla-4, etc., and what
is the sequence oftheir appearance? What is the precise role oftarget cell Class I and II
expression? What is the impact of present therapies on the immune system, and the
mechanisms thereof? What about future immunotherapies? Gene therapy? These and
other important questions will undoubtedly keep investigators occupied for a long time
to come.
I want to thank all the chapter authors (selected on the basis of their world
renowned expertise in the field) for their warm cooperation throughout this project,
and for the high quality oftheir contributions. I am also indebted to the overall editor
of this series, Dr. Michael Conn, particularly for bis forebearance, and to Mr. Paul
Dolgert and Ms. Debra Koch of Humana Press, for their attention to detail. I am also
gratend to Mrs. Josie Thomson for her excellent secretarial assistance.
Finally, I wish to dedicate this volume to the memory ofmy dear late wife, Ruth,
who died suddenly and unexpectedly in 1997. She was my most dedicated and single
minded loving supporter over my entire career, and her absence leaves a void in my life
that made it difficult forme to muster the resources to complete this project.
Contents Vll
REFERENCES
l. Vo1pe R. Autoimmunity in the Endocrine System, Monographs in Endocrino1ogy, No. 20, Springer
Verlag, Heide1berg, New York, 1981.
2. Vo1pe R. Autoimmunity and Endocrine Disease, Marce1 Dekker, New York, 1985.
3. Vo1pe R. Autoimmune Diseases of the Endocrine System. CRC Press, Boca Raton, FL, 1990.
Robert Volpe, MD
DEDICATION
This volume is dedicated with all my heart to my late wife, Ruth Pullan Volpe
(1927-1997).
CONTENTS
Prefaceoooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooo v
Dedication oooooooooooooooo oooooo ooooo oooooo ooooo viii
000000 00000 00000 0000000000 000000000000000 0 00000 00000 0000
Contributors xi
0 0 0 0 0 0 0 0 00 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 00 0 0 0 0 0 00 0 0 0 0 0 0 0 0 0 00 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 00 0 0 0 0 0 0 0 00 0 0 0
1 Normal Mechanisms for Self-Tolerance
0000000000000000000000000000000000000000001
Yoshinori Iwatani and Mikio Watanabe
2 Immunoregulation in Experimental Autoimmune
Endocrine Disease 31
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 00 00 0 0 0 0 0 0 0 0 0 00 0 0 0 00 0 0 0 0 0 0 0 00 0 0 0 0 0 0 0 0 0 00 0 0 0 0
Peter McCullagh
3 The Genetic Susceptibility to Type 1 (Insulin-Dependent)
Diabetes Mellitus and the Autoimmune Thyroid Diseases:
From Epidemiological Observations to Gene Mapping oo 57
0 0 0 0 000 0 0
Yaron Tomer, David Ao Greenberg, and Terry Fo Davies
4 Experimental Models for Autoimmune Thyroid Disease:
Recent Developments oooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooooo 91
Yi-chi M. Kong
5 Anima! Models for Insulin-Dependent Diabetes Mellitus 113
00000 000000
Sabine Bieg and Ake Lernmark
6 The Epidemiology of Autoimmune Thyroid Disease
000000000000000000141
Mark Po J. Vanderpump and W. Michael Go Tunbridge
7 Sex Hormones and Immune Responses 163
0 0 0 0 0 0 0 0 0 0 0 0 0 0 000 0 0 0 0 0 0 0 0 0 00 0 0 0 0 0 00 0 0 0 0
William J. Kovacs and Ndncy J. Olsen
8 Autoantigens in the Autoimmune Endocrinopathies oo Oooo oooooooooo 183
00 0
Jadwiga Furmaniak, Jane Sanders, and Bernard Rees Smith
9 The Immunology of Human Autoimmune Thyroid Disease oooooo 217
0
Robert Volpe
10 Thyroid-Associated Ophthalmopathy and Dermopathy 245
00000000000000
Anthony Po Weetman
11 Postparturn Autoimmune Endocrine Syndromes 271
00000000000000000000000 00
Nobuyuki Amino, Hisato Tada, and Yoh Hidaka
12 Etiology and Pathogenesis of Human
Insulin-Dependent Diabetes Mellitus OoOOOOOO ooooo ooooooooooo 293
0 0 00 0 00000 000 0
Jean-Fran9ois Bach
13 Autoimmune Adrenocortical Failure 309
00000000000000000 00000 000000000000000 0000000
Hemmo Ao Drexhage
14 Autoimmune Hypophysitis ooooooooooooooooooooooooooooooooooooooooooooooooooooooooooo 337
Shereen Ezzat and Robert Go Jasse
ix