Autoimmunity and the Thyroid (eBook)

Front Cover 1
Autoimmunity 
4 
Copyright Page 5
Table of Contents 6
Contributors 14
Preface 26
CHAPTER 1. HOW THYROID AUTOIMMUNITY WAS DISCOVERED: 
28 
CHAPTER 2. THE IMMUNOGENETIC BASIS OF AUTOIMMUNE THYROID DISEASE 36
I· INTRODUCTION 36
II· MAJOR HISTOCOMPATIBILITY COMPLEX AND IMMUNE REGULATION 37
III· IMMUNOGLOBULIN (Ig) AND IMMUNE REGULATION 40
IV. MHC ASSOCIATIONS WITH AUTOIMMUNE THYROID DISEASE 43
V. NON-MHC ASSOCIATIONS WITH AUTOIMMUNE THYROID DISEASE 51
VI· IMMUNOGLOBULIN (Ig) ALLOTYPE ASSOCIATIONS IN AUTOIMMUNE 
52 
VII. HLA AND Gm ALLOTYPE INTERACTION AFFECTING THE SUSCEPTIBILITY 
54 
VIII. MHC AND Ig GENE PRODUCTS INTERACTION IN AUTOIMMUNE 
56 
IX. SUMMARY 58
ACKNOWLEDGMENTS 58
XI· REFERENCES 59
CHAPTER 3. THE ROLE OF HLA-DR IN THE PATHOGENESIS 
64 
I. INTRODUCTION 64
II. AUTOANTIGENS AND MHC PRODUCTS ON THYROID CELL 
65 
III. ABERRANT EXPRESSION OF HLA-DR BY THYROID CELLS 66
IV. HYPOTHESIS 66
ACKNOWLEDGEMENTS 74
REFERENCES 74
CHAPTER 4. THE ROLE OF HUMAN THYROID CELL 
78 
INTRODUCTION 78
METHODOLOGY 79
RESULTS 82
DISCUSSION 87
SUMMARY 89
ACKNOWLEDGEMENTS 90
REFERENCES 90
CHAPTER 5. QUANTITATIVE AND QUALITATIVE ABNORMALITIES IN CIRCULATING LYMPHOCYTES IN AUTOIMMUNE 
94 
ACKNOWLEDGMENTS 102
REFERENCES 103
CHAPTER 6. ROLE OF ANTIGEN-SPECIFIC SUPPRESSOR T LYMPHOCYTES 
106 
GENERALIZED SUPPRESSOR T LYMPHOCYTES 106
ANTIGEN-SPECIFIC SUPPRESSOR T LYMPHOCYTE FUNCTION 108
ADTOANTIB0DY 
112 
DISCUSSION 115
SUMMARY 117
ADDENDUM 117
ACKNOWLEDGMENTS 117
REFERENCES 117
CHAPTER 7. CYTOTQXIC 
122 
I. INTRODUCTION 122
II. EXPERIMENTAL AND SPONTANEOUS THYROIDITIS IN ANIMALS 122
III. 
125 
SUMMARY 132
REFERENCES 133
CHAPTER 8. HUMORAL ASPECTS OF GRAVES' DISEASE 136
TSAb 138
TBI 145
ACKNOWLEDGMENTS 150
REFERENCES 150
CHAPTER 9. HUMORAL 
152 
INTRODUCTION 152
ELISA 154
RESULTS 155
DISCUSSION 160
ACKNOWLEDGMENTS 162
REFERENCES 162
CHAPTER 10. SIGNIFICANCE OF THYROID AUTOANTIBODIES IN AUTOIMMUNE THYROID 
166 
I. ANTI-THYROGLOBULIN (ANTI-Tg) ANTIBODIES 166
II. ANTI-MICROSOMAL (ANTI-M) ANTIBODIES 169
III. CLINICAL RELEVENCE OF ANTI-Tg AND ANTI-M ANTIBODY MEASUREMENTS 170
IV. THYROID CELL SURFACE ANTIBODIES 171
V. TSH RECEPTOR: ITS POSSIBLE ROLE AS THE ANTIGEN OF THYROID 
171 
VI. HUMORAL THYROID AUTOIMMUNE RESPONSE AND THYROID STATUS 172
VII. PRODUCTION OF ANTI-Tg AND ANTI-M ANTIBODIES IN PERIPHERAL 
174 
REFERENCES 175
CHAPTER 11. CHARACTERISATION OF THYROID AUTOANTIBODY 
HASHIMOTO'S DISEASES 180
I. INTRODUCTION 180
II. PATIENTS, METHODS AND 
181 
III. RESULTS 184
IV. DISCUSSION 196
ACKNOWLEDGEMENTS 199
REFERENCES 199
CHAPTER 12. NEW METHODS OF DETECTING THYROID AUTOANTIBODIES 
202 
I. INTRODUCTION 202
II. ANTIBODIES TO THE HUMAN THYROID MICROSOME 203
III. ANTIBODY ACTIVITY TO FAT CELL MEMBRANE PREPARATIONS 207
IV. AUTOANTIBODY SYNTHESIS IN VITRO: A SHORT-TERM CULTURE ANDELISA SYSTEM 210
V. CONCLUSIONS 212
ACKNOWLEDGEMENTS 213
REFERENCES 213
CHAPTER 13. SIGNIFICANCE OF THYROID HORMONE AUTOANTIBODIES 216
I. DETECTION OF TH ANTIBODIES 217
II. SPECIFICITY OF THYROID HORMONE-AUTOANTIBODIES 218
III. NATURE OF THE TH ANTIBODIES 219
IV. ASSOCIATION CONSTANTS AND BINDING CAPACITIES OF 
220 
V. PATHOPHYSIOLOGIC EFFECTS 222
VI. INCIDENCE OF CIRCULATING TH ANTIBODIES 226
VII. IS THYROGLOBULIN THE ANTIGEN INDUCING TH 
228 
VIII. SIGNIFICANCE OF TH ANTIBODIES 233
ACKNOWLEDGMENTS 239
REFERENCES 239
CHAPTER 14. NEW PROCEDURES FOR DETECTING 
244 
INTRODUCTION 244
THE FRTL-5 THYROID CELL 245
MONOCLONAL ANTIBODY STUDIES, THE TSH RECEPTOR AND GRAVES' 
246 
NEW ASSAYS BASED USING FRTL-5 CELLS 259
THE FUTURE OF THESE ASSAYS 270
REFERENCES 271
CHAPTER 15. STRUCTURE, SYNTHESIS, CELLULAR LOCALIZATION 
276 
INTRODUCTION 276
STRUCTURE OF THE TSH RECEPTOR 277
BIOSYNTHESIS OF THE TSH RECEPTOR 280
NATURAL AND EXPERIMENTALLY RAISED ANTI-TSH RECEPTOR ANTIBODIES 282
IMMUNOCYTOCHEMICAL STUDIES OF THE TSH RECEPTOR 294
REFERENCES 297
CHAPTER 16. SIGNIFICANCE OF REMISSION IN GRAVES' DISEASE 300
I. INTRODUCTION 300
II. DEFINITION OF REMISSION 300
III. ABNORMALITIES OF THYROID FUNCTION IN UNTREATED THYROTOXIC 
301 
IV. CLINICAL COURSE OF GRAVES' DISEASE BEFORE THYROTOXICOSIS 302
V. CLINICAL COURSE OF GRAVES' DISEASE AFTER THIONAMIDE THERAPY 304
VI. DURATION OF TREATMENT 308
VII. SIGNIFICANCE OF REMISSION 312
VIII. SUMMARY 313
REFERENCES 314
CHAPTER 17. POSTPARTUM AUTOIMMUNE THYROID SYNDROMES 316
1. INTRODUCTION 316
2. HASHIMOTO'S DISEASE AND PREGNANCY 317
3. GRAVES1 DISEASE AND PREGNANCY 317
4. VARIOUS TYPES OF THYROID DYSFUNCTION 319
5. INCIDENCE OF POSTPARTUM THYROID DYSFUNCTION 320
6. PREDICTION OF POSTPARTUM THYROID DYSFUNCTION 322
7. MECHANISM IN POSTPARTUM 
326 
8. NEONATAL THYROID DISEASE DUE TO ANTIBODY TRANSFER 334
SUMMARY 340
ACKNOWLEDGEMENTS 340
REFERENCES 340
ACKNOWLEDGMENT OF PERMISSION 341
Part I: Short Communications 
342 
CHAPTER 18. A LONGITUDINAL STUDY OF THYROID AUTOIMMUNITY AND SUBCLINICAL HYPOTHYROIDISM IN A RANDOM POPULATION OF CENTRAL ITALY 344
I. INTRODUCTION 344
II. SELECTION OF THE SAMPLE 345
III. LABORATORY METHODS 345
IV. THYROID AUTOIMMUNITY 345
V. SUBCLINICAL HYPOTHYROIDISM 345
REFERENCES 345
CHAPTER 19. LITHIUM THERAPY INDUCES AUTOIMMUNE THYROID DISEASE 346
Materials and Methods 346
Results 347
Discussion 347
REFERENCES 347
CHAPTER 20. AUTOIMMUNE THYROIDITIS ASSOCIATED WITH MELASMA IN NON-PREGNANT WOMEN 348
Patients and Methods 348
Results 349
Conclusions 349
REFERENCES 349
CHAPTER 21. DETECTION OF ANTI-THYROID MEMBRANE ANTIBODY IN GRAVES' PATIENTS 350
I. INTRODUCTION 350
II. MATERIALS AND METHODS 350
III. RESULTS AND DISCUSSION 351
CHAPTER 22. RELEVANCE OF A CIRCULATING IMMUNE COMPLEX ASSAY (CIC) TO DISTINGUISH BETWEEN PATIENTS WITH AUTOIMMUNE THYROID DISEASES AND HEALTHY CONTROLS 352
INTRODUCTION 352
RESULTS 353
DISCUSSION AND CONCLUSION 353
ACKNOWLEDGMENT 353
CHAPTER 23. THYROTROPIN-RECEPTOR COMPLEX BINDING ANTIBODIES IN AUTOIMMUNE THYROID DISEASES 354
REFERENCES 355
CHAPTER 24. THYROID GROWTH STIMULATING IMMUNOGLOBULINS IN PATIENTS OF AN IODINE-DEFICIENT GOITRE REGION ESTIMATED BY H-THYMIDINE INCORPORATION INTO ISOLATED PORCINE THYROID FOLLICLES 356
Material and methods 356
Results 356
Discussion 356
References 357
CHAPTER 25. AN ANTIBODY TO EYE MUSCLE IN GRAVES' OPHTHALMOPATHY 360
INTRODUCTION 360
RESULTS 360
DISCUSSION 361
REFERENCES 361
CHAPTER 26. ANALYSIS OF NONSPECIFIC REACTION IN ENZYME LINKED IMMUNOSORBENT ASSAY TESTING FOR HUMAN EYE MUSCLE SPECIFIC ANTIBODIES IN GRAVES' OPHTHALMOPATHY AND HASHIMOTO'S THYROIDITIS 362
CHAPTER 27. TISSUE CROSS-REACTIVITY OF MOUSE AND HUMAN MONOCLONAL AND POLYCLONAL ANTIBODIES AGAINST HUMAN ORBITAL TISSUE ANTIGENS 364
MATERIALS AND METHODS 364
RESULTS 364
DISCUSSION 366
REFERENCES 367
CHAPTER 28. DECREASE OF PERIPHERAL LARGE GRANULAR LYMPHOCYTES IN GRAVES DISEASE 368
INTRODUCTION 368
METHODS AND RESULTS 368
REFERENCES 369
CHAPTER 29. T-SUPPRESSOR CELL DEFECTS IN SPORADIC NONTOXIC GOITER DISEASE 370
CHAPTER 30. LYMPHOCYTE MIGRATION INHIBITION IN AUTOIMMUNE THYROID DISEASE 372
INDIRECT MIGRATION INHIBITION TEST 372
DIRECT MIGRATION INHIBITION TEST 372
REFERENCES 373
CHAPTER 31. CYTOTOXICITY IN HASHIMOTO'S THYROIDITIS 374
RESULTS 375
DISCUSSION 375
CHAPTER 32. THYROID ANTIGEN-INDUCED LEUKOCYTE PROCOAGULANT ACTIVITY: A NOVEL APPROACH TO THE STUDY OF CELL-MEDIATED IMMUNITY IN GRAVES' DISEASE AND HASHIMOTO'S THYROIDITIS 376
INTRODUCTION 376
PATIENTS AND METHODS 376
RESULTS 377
DISCUSSION 377
REFERENCES 377
CHAPTER 33. THE PRODUCTION AND PROPERTIES OF MONOCLONAL MOUSE ANTIHUMAN MICROSOMAL ANTIBODIES 378
PRODUCTION OF MAHM ANTIBODIES 378
PROPERTIES OF MAHM ANTIBODIES 379
REFERENCES 379
CHAPTER 34. AUTO-AND HETEROANTIBODIES AGAINST HUMAN THYROGLOBULIN EXHIBIT SIMILAR HETEROGENEITY AND FINE SPECIFICITIES 380
REFERENCES 382
CHAPTER 35. ACCUMULATION OF ANTI-THYROGLOBULIN (Tg) ANTIBODY BY NORMAL THYROID CELLS OF MONOLAYER CULTURE 384
I. INTRODUCTION 384
II. MATERIALS AND METHODS 384
III. RESULTS AND DISCUSSION 385
CHAPTER 36. PARTICIPATION OF Ir-GENE(S) ON THE PRODUCTION OF ANTI-TEOTOID HARMONE ANTIBODIES 386
I. INTRODUCTION 386
II. MATERIALS, METHODS AND RESULTS 386
III. SUMMARY 387
REFERENCES 387
CHAPTER 37. IN SITU EXPRESSION OF HLA ANTIGENSIN GRAVES'DISEASE 388
I. INTRODUCTION 388
II. MATERIAL AND METHODS 388
III. RESULTS 389
REFERENCES 389
CHAPTER 38. IMMUNOGLOBULIN ALLOTYPES AND HLA-DR IN DIFFUSE AND MULTINODULAR SIMPLE GOITER DISEASE, GRAVES THYROTOXICOSIS AND ENDOCRINE OPHTHALMOPATHY 390
CHAPTER 39. GENETIC MARKERS AND GRAVES' DISEASE : STUDY OF THE FOURTH COMPONENT COMPLEMENT ALLELES (C4) 392
CHAPTER 40. HLA-ASSOCIATED MALE SUSCEPTIBILITY TO THYROID AÜTOANTIBODY PRODUCTION IN A SELECTED POPULATION 394
METHODS 395
RESULTS 395
DISCUSSION 396
REFERENCES 396
CHAPTER 41. INFLUENCE OF HLA-DR4 ON THE DEVELOPMENT OF AUTOIMMUNE POSTPARTUM THYROIDITIS1 398
SUBJECTS & METHODS
RESULTS & DISCUSSION
REFERENCES 399
CHAPTER 42. HLA ANTIGENS IN THYROIDITIS: DIFFERENCES BETWEEN SILENT AND POSTPARTUM LYMPHOCYTIC FORMS, AND COMPARISON WITH SUBACUTE AND GOITROUS AUTOIMMUNE THYROIDITIS 400
MATERIALS AND METHODS 401
RESULTS 401
DISCUSSION 401
REFERENCES 402
CHAPTER 43. RABBITS IMMUNIZED WITH TSH PRODUCE THYROID-STMJLATING ANTIBODIESl 404
INTRODUCTION 404
METHODS & RESULTS
DISCUSSION 405
ACKNOWLEDGMENTS 405
REFERENCES 406
CHAPTER 44. IDENTIFICATION OF THYROID AUTOANTIGENS AND PRECIPITATION OF THE TSH RECEPTOR BY GRAVES' DISEASE IMMUNOGLOBULINS 408
REFERENCES 409
CHAPTER 45. The Development Of Monoclonal Antibodies Directed Against Anti-TSH Receptor Antibodies 410
INTRODUCTION 410
METHODS 410
RESULTS 411
DISCUSSION 411
REFERENCES 412
CHAPTER 46. PREPARATION OF BIOTINYLATED RECEPTOR PURIFIED GRAVES' IgG: A SIMPLE TECHNIQUE ALLOWING DIRECT FUNCTIONAL ASSESSMENT OF TSH RECEPTOR ANTIBODY INTERACTION WITH MEMBRANES 414
MATERIALS AND METHODS 414
RESULTS 415
DISCUSSION 415
REFERENCES 416
CHAPTER 47. STIMULATION OF IODINE ORGANIFICATION IN CULTURED PORCINE THYROID CELLS BY GRAVES' IMMUNOGLOBULINS 418
INTRODUCTION 418
MATERIALS AND METHODS 419
SUMMARY 419
CONCLUSION 420
REFERENCES 420
CHAPTER 48. EVALUATION OF STIMULATING EFFECTS OF GRAVES1 IgG USING VARIOUS THYROID PREPARATIONS 422
I. INTRODUCTION 422
II. MATERIALS AND METHODS 422
III. RESULTS 423
CHAPTER 49. DEMONSTRATION OF HETEROGENEITY IN THYROTROPIN DISPLACING (TDI) OR THYROID STIMULATING IMMUNOGLOBULINS (TSI) IN SERA OF PATIENTSWITH GRAVES' DISEASE BY FOUR DIFFERENT ASSAY METHODS. 424
INTRODUCTION 424
MATERIALS AND METHODS 424
RESULTS 425
DISCUSSION 425
REFERENCES 426
CHAPTER 50. AN IMPROVED METHOD FOR THE DETECTION OF THYROID HORMONE AUTOANTIBODIES ( THAA ) IN SERUM 428
I. INTRODUCTION 428
II. MATERIALS AND METHODS 428
III. RESULTS AND DISCUSSION 429
References 429
CHAPTER 51. TWO CASES ASSOCIATED WITH THYROID HORMONE AUTOANTIBODIES 430
I. INTRODUCTION 430
II. CASE REPORT 430
III. DISCUSSION 431
REFERENCES 431
CHAPTER 52. T4 ANTIBODIES AND THYROXINE-BINDING GLOBULIN (TBG) IMMUNORADIOMETRIC ASSAY 432
PATIENTS and METHODS 432
COMMENT 433
REFERENCES 433
CHAPTER 52. PRODUCTION OF ANTI-RABBIT THYRDOEJOBULIN AND ANTI-THYROID HOHVOSE ANTIBODIES IN RABBITS 
434 
I . INTRODUCTION 434
II. MATERIALS, METHODS AND RESULTS 434
III. SUMMARY 435
REFERENCES 435
CHAPTER 54. EFFECTS OF ANTITHYROID DRUGS (MMI & PTU) ON CONCANAVALIN AINDUCED SUPPRESSOR CELL ACTIVITY IN STUDIES WITH MURINE SPLEEN CELLS
INTRODUCTION 436
MATERIALS AND METHODS 436
RESULTS AND DISCUSSION 436
REFERENCES 437
CHAPTER 55. CORRELATION OF THYROID SUPPRESSIBILITY AND DETERMINATION OF THYROTROPIN BINDING INHIBITING ANTIBODIES (TBIAb)AT THE END OF ANTITHYROID DRUG TREATMENT IN PATIENTS WITH GRAVES'DISEASE 438
RESULTS 439
REFERENCES 439
CHAPTER 56. SERUM THYROGLOBULIN LEVELS IN PATIENTS WITH GRAVES' DISEASE TREATED WITH METHIMAZOLE: CORRELATION WITH THYROID-STIMULATING AND TSH-BINDING INHIBITING IMMUNOGLOBULINS 440
I. INTRODUCTION 440
II. MATERIAL AND METHODS 441
III. RESULTS 441
IV. DISCUSSION 442
V. REFERENCES 443
CHAPTER 57. RELATIONSHIP OF DISEASE ACTIVITY AND ALTERED BALANCE OF PERIPHERAL T LYMPHOCYTE SUBSETS IN GRAVES' DISEASE TREATED WITH THIONAMIDE DRUGS 444
REFERENCE 445
CHAPTER 58. TSAb AND T LYMPHOCYTES SUBSET CHANGES IN PATIENTS WITH GRAVES' DISEASE (GD) TREATED BY CARBIMAZOLE (C) 446
INTRODUCTION 446
PATIENTS 446
METHODS 446
RESULTS 447
COMMENTS AND CONCLUSION 447
CHAPTER 59. PERIPHERAL T-LYMPHOCYTE SUBSETS BEFORE AND DURING CARBTMAZOLE THERAPY IN PATIENTS WITH GRAVES' DISEASE (GD) 448
SUBJECTS AND METHODS 448
RESULTS AND COMMENT 449
CHAPTER 60. INCREASE OF T8 CELLS DURING TREATMENT COURSE AND IN REMISSION IN A PROSPECTIVE STUDY OF MEDICAL TREATMENT FOR GRAVES' DISEASE 452
CHAPTER 61. GRAVES' DISEASE AND HASHIMOTO'S THYROIDITIS: EFFECTS OF HIGH DOSES OF ANTITHYROID DRUGS ON THYROIDAL ANTIBODIES 454
INTRODUCTION 454
PATIENTS AND METHODS 454
RESULTS 455
DISCUSSION 456
REFERENCES 456
CHAPTER 62. IN VIVO EFFECTS OF METHIMAZOLE AND THYROXINE ON THYROID MICROSOMAL ANTIBODY TITERS IN HASHIMOTO'S THYROIDITIS1 458
SUBJECTS & METHODS
RESULTS 459
DISCUSSION 459
CHAPTER 63. PROGNOSTIC FACTORS IN GRAVES' DISEASE 460
SUBJECTS & METHODS
RESULTS 461
DISCUSSION 461
CHAPTER 64. THYROID ANTIBODIES (TAb) AND OUTCOME OF GRAVES' DISEASE 462
PATIENTS and METHODS 462
COMMENT 463
REFERENCES 463
CHAPTER 65. SERUM .-GLUTAMYLTRANSPEPTIDASE (GGT) AND ALKALINE PHOSPHATASE (ALP): RELATION WITH THE OUTCOME OF GRAVES' DISEASE 464
PATIENTS and METHODS 464
COMMENT 465
REFERENCES 465
CHAPTER 66. EFFECT OF PARTIAL THYROIDECTOMY ON ANTIBODY ACTIVITY IN GRAVES1 DISEASE 466
BACKGROUND 466
MATERIAL & METHODS
RESULTS 467
DISCUSSION 467
REFERENCES 467
CHAPTER 67. RADIOIODINE THERAPY AND SERUM LATS-PROTECTOR 468
I. THE BACKGROUND 468
II. PLAN OF STUDY 468
III. RESULTS 469
IV. CONCLUSIONS 469
REFERENCES 469
Index 470