Principles and Methods for Assessing Autoimmunity Associated with Exposure to Chemicals: Environmental Health Criteria Series No. 236 (Environmental Health Criteria)

TITLE......Page 1
COPYRIGHT......Page 2
CONTENTS......Page 3
NOTE TO READERS OF THE CRITERIA MONOGRAPHS......Page 10
PREAMBLE......Page 11
WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA ON PRINCIPLES AND METHODS FOR ASSESSING AUTOIMMUNITY ASSOCIATED WITH EXPOSURE TO CHEMICALS......Page 16
ACRONYMS AND ABBREVIATIONS......Page 22
1. SUMMARY......Page 27
2. INTRODUCTION AND DEFINITIONS OF AUTOIMMUNITY AND AUTOIMMUNE DISEASE......Page 31
3.1 Introduction......Page 35
3.2 The innate immune response......Page 36
3.3.1 Function......Page 37
3.3.2 Aberrant function......Page 40
3.3.3 Ageing......Page 41
3.4 Mechanisms of self-tolerance......Page 42
3.5.1 Mechanisms of induction......Page 44
3.5.2 Effector mechanisms......Page 47
3.6 Summary......Page 48
4.1.1 Probable monogenic autoimmune syndromes......Page 50
4.1.2 Multigenic autoimmune diseases......Page 52
4.1.2.1 Immune deficiencies......Page 53
4.1.2.2 Defects and dysregulation in apoptosis pathways and cell cycle regulation......Page 55
4.1.2.3 Associations with MHC alleles or haplotypes......Page 57
4.1.2.4 Polymorphisms in genes coding for regulatory and effector molecules of the immune system......Page 61
4.1.2.5 Hormones and genes......Page 63
4.1.2.6 Genetic polymorphisms of xenobiotic-metabolizing enzymes......Page 64
4.1.2.7 Genes coding for autoantigens......Page 65
4.1.2.8 Genes coding for enzymes involved in post-translational modification of autoantigens......Page 66
4.1.3 Problems and perspectives......Page 67
4.2.1.1 Suppression of autoimmunity......Page 68
4.2.1.2 Stimulation of autoimmunity......Page 69
4.2.2 Psychological stress......Page 72
5.1 Introduction......Page 73
5.2 Addison disease......Page 76
5.3 ANCA-associated vasculitis......Page 77
5.4 Antiphospholipid syndrome......Page 78
5.5 Coeliac disease......Page 79
5.6 Diabetes mellitus......Page 80
5.7 Goodpasture disease......Page 81
5.8 Guillain-Barré syndrome......Page 82
5.9.1 Warm autoimmune haemolytic anaemia......Page 83
5.9.2 Cold autoimmune haemolytic anaemia......Page 84
5.10 Autoimmune hepatitis......Page 85
5.11.1 Crohn disease......Page 87
5.11.2 Ulcerative colitis......Page 88
5.12 Multiple sclerosis......Page 89
5.13 Myasthenia gravis......Page 90
5.15 Autoimmune myositis......Page 92
5.16 Paraneoplastic neurological syndromes......Page 93
5.17 Pemphigus/pemphigoid......Page 94
5.17.1 Pemphigus......Page 95
5.18 Pernicious anaemia......Page 96
5.19.1 APGS type 1......Page 97
5.20 Primary biliary cirrhosis......Page 98
5.21 Psoriasis......Page 99
5.22 Rheumatoid arthritis......Page 100
5.23 Scleroderma (systemic sclerosis)......Page 101
5.24 Sjögren syndrome......Page 103
5.25.1 Systemic lupus erythematosus......Page 104
5.25.2 Lupus syndrome......Page 105
5.26.1 Immune thrombocytopenic purpura......Page 106
5.26.3 Drug-induced thrombocytopenia......Page 107
5.27 Autoimmune thyroid diseases......Page 108
5.27.2 Hashimoto thyroiditis......Page 109
5.27.3 Iodine and thyroid disease......Page 110
5.28 Diseases with autoimmune components......Page 111
6.1 Descriptive epidemiology......Page 113
6.1.1 Demographic patterns......Page 115
6.1.2 Co-morbidity of autoimmune diseases......Page 117
6.2.1 Prevalence of autoantibodies in the general population......Page 118
6.2.2 Associations between autoantibodies and environmental exposures......Page 120
7.1 General......Page 122
7.2.1 Formation of neoantigens......Page 124
7.2.2 Cross-reactivity......Page 125
7.2.3 Release of non-tolerant epitopes......Page 126
7.2.4 Interference with central tolerance......Page 127
7.2.5.1 Importance of signal 2......Page 128
7.2.5.2 Induction of signal 2......Page 129
7.2.6 Immunoregulation......Page 130
7.3 Other mechanisms......Page 132
8.1 Toxic oil syndrome......Page 133
8.1.1 Clinical features of toxic oil syndrome......Page 134
8.1.2 Immune markers in toxic oil syndrome......Page 135
8.1.3 Experimental studies of toxic oil syndrome......Page 137
8.2 TCDD (dioxins)......Page 140
8.3.1 General......Page 141
8.3.2 Hexachlorobenzene......Page 143
8.3.2.2 Adverse immune effects of hexachlorobenzene......Page 144
8.5.1 Introduction to epidemiological studies of silica exposure......Page 148
8.5.2 Occupational silica exposure and systemic autoimmune diseases......Page 150
8.5.3 Experimental studies of immune- and autoimmune-related effects of silica......Page 153
8.5.4 Summary......Page 156
8.6.1 Mercury......Page 157
8.6.3 Cadmium......Page 161
8.6.4 Other heavy metals......Page 162
8.7 Solvents......Page 164
8.8 Tobacco smoke......Page 167
8.9 Ethanol......Page 171
8.10 Iodine......Page 174
8.11.1 General......Page 175
8.11.2 Hydralazine......Page 176
8.11.3 Procainamide......Page 177
8.11.4 D-Penicillamine......Page 178
8.11.6 Gold drugs......Page 179
8.11.7 Biopharmaceuticals......Page 181
8.11.8.1 Diethylstilbestrol-induced immune alterations......Page 182
8.11.8.2 Immune effects of diethylstilbestrol in humans......Page 183
8.12.1 Introduction......Page 185
8.12.2 Silicone breast implants and systemic disease......Page 186
8.12.3 Conclusion......Page 188
9.1 Infections: cause of autoimmunity, and immune programming......Page 189
9.1.1 Streptococcus and rheumatic fever......Page 191
9.1.2 Hepatitis C virus......Page 192
9.1.4 Other infections......Page 193
9.1.5 Absence of infections: the hygiene hypothesis......Page 194
9.2.1 Vaccines themselves......Page 195
9.2.2 Vaccine additives......Page 196
9.3 Dietary factors......Page 197
9.3.2 Dietary fat and fatty acid content......Page 198
9.3.4 Vitamin D......Page 200
9.3.5 L-Tryptophan and eosinophilia myalgia syndrome......Page 201
10.1 Introduction......Page 204
10.2.1 The Brown Norway rat model......Page 206
10.2.1.1 Metals......Page 207
10.2.1.3 Hexachlorobenzene......Page 208
10.3 Mouse models......Page 209
10.3.2 Drugs......Page 210
10.3.3 Pristane......Page 211
10.4.1 Systemic lupus erythematosus-prone strains of mice......Page 212
10.5 Other species......Page 213
10.6.2 Primary, secondary, and adoptive popliteal lymph node assays and the lymph node proliferation assay......Page 214
10.6.3 Reporter antigen popliteal lymph node assay......Page 215
10.7 Testing strategy......Page 217
11.1 Introduction......Page 219
11.2.2 Counter-immunoelectrophoresis......Page 221
11.2.3 Haemagglutination......Page 222
11.2.4 Enzyme-linked immunosorbent assay/fluorescent enzyme immunoassay......Page 223
11.2.5 Radioimmunoassay......Page 224
11.2.7 Multiplex analysis......Page 225
11.3.1 Autoantigens......Page 226
11.3.2 Anti-immunoglobulin reagents......Page 228
11.4 Clinical interpretation......Page 229
11.5.1 Autoimmune disease and human immunoglobulin levels......Page 230
11.5.2 Quantification of human immunoglobulins......Page 231
11.6 Testing in the diagnosis of delayed-type chemical hypersensitivity......Page 233
11.7 Conclusions......Page 234
12.1 Introduction......Page 237
12.2 Hazard identification of chemical-induced autoimmune disease (animal models)......Page 238
12.4 Mode of action......Page 239
12.5 Epidemiological issues......Page 241
12.6 Susceptibility factors......Page 242
12.7 Burden of autoimmune disease......Page 243
13.1 Conclusions......Page 245
13.2 Recommendations......Page 246
TERMINOLOGY......Page 248
REFERENCES......Page 282
RESUME......Page 351
RESUMEN......Page 356