AUTOIMMUNE

DISEASE
Santoso Cornain MD,DSc
Laboratory of Immunopathology,
Faculty of Medicine, University of Indonesia
 Autoimmune response
 Autoimmune response / Autoimmunity :
= acquired immune response to self
antigens;
- autoimmune reaction  tissue damage
 autoimmune disease;
 Prevalence: 1-2 % in USA or 3.5 % in UK;
- 94 % Graves’s disease / hyperthyroidism,
Type I diabetes mellitus (DM), pernicious
anemia, rheumatoid arthritis (RA), thyroiditis,
vitiligo, multiple sclerosis (MS), systemic lupus
erythematosus (SLE);
 Mechanisms of development (1)
 1. Breakdown of self tolerance
 2. Molecular mimicry and T cell bypass
  cross reacting antigen of microbial antigen 
 autoantibody response;
 e.g. heart autoantibody in post group A streptococcal
 rheumatic fever;
 3. Defective regulation mediated via helper T cells
  microbial infection  Th1 (pro inflammatory cytokines)
 and Th2 (anti inflammatory cytokines and antibody formation),
 predominance of Th1 or Th2 due certain situation (e.g. pregnancy)
  autoimmunity (RA and SLE);
 4. Polyclonal activation via microbial antigens
  some microbes  polyclonal activators e.g. E. coli LPS, EBV;
  I.M. (infectious mononucleosis)  anti DNA antibody;
(Adapted from Lydyard PM et al. Instant Notes in Immunology 2000)
(Adapted from Lydyard PM et al. Instant Notes in Immunology 2000)
 Mechanisms of development (2)
 5. Modification of cell surfaces by microbes and drugs
  viruses or drugs  attached to surface in hapten like
 manner  alter specificity;
 e.g. thrombocytopenia and anemia in viral infection or
 drug induced;
 6. Availability of normally sequestered self antigen
  anatomically separated (sequestered) antigens
 (lens, CNS, thyroid, testes)  trauma or infection 
 released or presented  autoimmunity;
 7. Dysregulation of the idiotype network
  immune response to hormone  anti hormone
 antibody
  anti-idiotype antibody  interact with the receptor
  autoimmune disease;
 e.g. Antibodies to insulin and acetylcholine receptor
(Adapted from Lydyard PM et al Instant Notes in Immunology 2000)
 Spectrum / Classification of
Autoimmune DIsease
 1. Organ specific:
= involving certain organ with auto-
antibody specific to that organ (organ
specific autoantibody);
 2. Non-organ specific:
= involving various organs with auto-
antibodies specific to various organs
(non-organ specific autoantibodies);
 3. Combination / overlap between ad 1) and ad 2):
= involving more than one type with both
types of autoantibodies
 (1). Organ specific auto-immune diseases
 Disease  Autoantigens targeted

 Organ specific:
1. Myasthenia gravis 1. Acethylcholine receptor
2. Graves’ disease 2. Thyroid stimulating hormone rec.
3. Hashimoto’s thyroiditis 3. Thyroid peroxidase thyroglobulin
4. Type I diabetes 4. Islet cell cytopl. Insulin, GAD
5. Pernicious anemia 5. HK ATPase (GPP), intrinsic factor
6. Addison’s disease 6. 17 hydroxylase
7. Pemphigus vulgaris
7. 130 kDa cadherin adhesion mol.
8. Bulbous pemphigoid
8. 160 kDa & 230 kDa cell adhesion
molecules
9. Vitiligo
9. Melanocyte cytoplasmic antigen
10. Autoimmune hepatitis
10. Asialoglycoprotein rec,
11. Autoimmune hemolytic anemia Cytochrome P450206
11. Red blood cell surface antigen
(Adapted from Lydyard PM et al. Instant Notes in Immunology 2000)
(Adapted from Lydyard PM et al. Instant Notes in Immunology 2000)
(2). Non-organ specific autoimmune diseases
 Disease
 Non-organ specific
 1. Rheumatoid arthritis
 2. Systemic lupus
 erythematosus
 3. Sjogren’s syndrome
 4. Systemic sclerosis
 5. Mixed connective tissue
 disease
 6. Polymyositis
 Main autoantigens targeted
 1. IgG
 2. ds DNA, Sm, SS-A (Ro: a
 60 kDa ribonucleo-
 protein), SS-B (La: a 47 kDa
 ribo-nucleoprotein), histones
 3. SS-A, SS-B
 4. DNA topoisomerase I,
 centromere
 5. 70 kDa small nuclear ribo-
 nucleoprotein
 6. tRNA synthetase
(3). Overlap between organ- and non-organ
specific autoimmune diseases
 Disease  Main autoantigens targeted
 Overlap of organ- non-
organ specific
 1. Primary biliary cirrhosis  1. Mitochondrial pyruvate
 dehydrogenase
 2. Systemic lupus  2. Non-collagenous domain
 erythematosus  of type IV collagen in renal
 and lung basement
 membrane
(4). Autoimmune diseases might occur in more than one type
e.g. thyroiditis autoimmune disease and gastric autoimmunity
Pathogenesis of autoimmune diseases

 1. primarily by antibody (auto-antibody):

 e.g. hemolytic anemia
 2. primarily by cellular immunity (auto-
 reactive T cell):
 e.g. multiple sclerosis
 3. combination of antibody and cell mediated
 immunity:
 e.g. rheumatoid arthritis
Factors contributing to autoimmune diseases (1)

 Autoimmunity arises as the results of a breakdown

of self tolerance;
 Autoimmune disease is a multifactorial disease;
 Factors:
 1. age  more in older age
 2. gender  F/M ratio 7-10/1
 3. genetics  HLA linked
 4. infections  viral (EBV), bacterial
 5. the nature of autoantigens  sequestered Ag
 6. drugs  procainamide  SLE like
 7. immunodeficiency  cellular immunodef.
Autoimmune diseases and HLA association
(Caucasians)
 Disease HLA Relative
 Risk
 -----------------------------------------------------------------
 Ankylosing spondylitis B27 90
 Reiter’s disease B27 36.0
 Systemic lupus erythematosus DR3 15
 Myastenia gravis DR3 2.5
 Juvenile diabetes mellitus DR3/ 25
 (insulin dependent) DR4
 Psoriasis vulgaris DR4 14
 Multiple sclerosis DR2 5
 Rheumatoid arthritis DR4 4
 Viral and bacterial sequences that cross react
with autoantigens
 Disease Autoantibody Autoantigen Microbe

 1. Chagas disease Heart autoAb Laminin T. cruzi

 2. Post streptococcal Heart autoAb Myosin, tropo- Group A
 rheumatic fever myosin streptococci
3. Autoimmune Liver Kidney Cytochrome HSV-1,HCV
 hepatitis microsomal Ab P450206
 4. Ankylosing Anti-HLA B27 HLA B27 Klebsiella
 spondylitis pnemoniae
 nitrogenase
 5. Coeliac disease Anti-A-gliadin A-gliadin Adenovirus 12
 6. Type I diabetes Anti-glutamic Glutamic acid Coxsackie B4
 acid decarboxylase decarboxylase