II. Epidemiology
- Women account for 75% of Autoimmunity
- Age of onset is most common in young adult women
III. Physiology: Self-Tolerance
- Background
- Self-Tolerance prevents immune response to self-Antigens (body fighting itself)
- Central Tolerance (eliminate autoreactive cells that attack self)
- T-Cells (Thymus)
- B-Cells (Bone Marrow)
- Autoreactive B-Cells are eliminated (apoptosis) before release into peripheral circulation (negative selection) OR
- Receptor Editing allows B Cells to redefine Ig Light chain, and therefore no longer self-reactive
- Peripheral Tolerance (immunologically deactive autoreactive cells)
- T-Cells
- B-Cells
- T-Helper Cells are typically absent for self-Antigen, and the autoreactive B-Cells remain inactive or die
IV. Risk Factors
-
Genetic Predisposition to Autoimmunity
- Major Histocompatibility Complex (MHC) Defects - Human Leukocyte Antigen (HLA) I and II specific allotypes
- Example: Type 1 Diabetes Mellitus is associated with DR3 and DR4 HLA types
- Non-MHC Genetic Defects
- Major Histocompatibility Complex (MHC) Defects - Human Leukocyte Antigen (HLA) I and II specific allotypes
- Environmental Predisposition to Autoimmunity
- Infectious Disease (e.g. Coxsackie Virus B and Type 1 Diabetes Mellitus)
V. Mechanism
- Mediators of Autoimmunity
- Mechanisms
- Molecular mimicry
- Polyclonal Lymphocyte activation
- Polyclonal activators (e.g. EBV, CMV) non-specifically activate B-Cells including autoreactive cells
- Other polyclonal activators (e.g. lectin plant Protein including PHA) activate T Cells
- Sequestered Antigen Release
- Non-exposed tissue Antigens (e.g. behind blood-brain barrier) may be exposed with injury (e.g. Head Injury)
- Antigen Spreading
- Predisposing factors
- Autoimmunity increases with age: lower self tolerance
- Genetic predisposition
- Protective factors
- Autoimmunity less common where high Antigen exposure
- Protective exposures in first year of life
- Eating dirt
- Living on a farm
- House pet
- Day care
- References
VI. Associated Conditions: Dermatologic Autoimmune Conditions
- Psoriasis
- Dermatitis herpeteformis
- Pemphigus Vulgaris
- Vitiligo
- Alopecia Areata
VII. Associated Conditions: Endocrine Autoimmune Conditions
-
Insulin Dependent Diabetes Mellitus
- Autoantibody to Pancreatic Beta Cell Antigens
-
Grave's Disease
- Autoantibody: TSH Receptor Antibody (Thyroid Stimulating Immunoglobulin)
-
Hashimoto's Thyroiditis
- Autoantibody: Antithyroid Peroxidase Antibody (TPO Antibody) and Antithyroglobulin Antibody (TgAb)
- Thyroid tissue infiltration and destruction by B-Cells and CD4+ T Cells
-
Addison's Disease
- Autoantibody to Adrenal cytoplasmic P450 Antigens
VIII. Associated Conditions: Gastrointestinal Autoimmune Conditions
- Crohn's Disease
- Ulcerative Colitis
- Primary Biliary Cirrhosis
- Autoantibody to Centromere
-
Autoimmune Hepatitis
- Autoantibody to hepatocyte Antigens
IX. Associated Conditions: Hematologic Autoimmune Conditions
- Autoimmune Hemolytic Anemia
- Autoimmune Thrombocytopenia
-
Pernicious Anemia
- Autoantibody to Gastrointestinal Intrinsic Factor and parietal cells
X. Associated Conditions: Musculoskeletal Autoimmune Conditions
- Ankylosing Spondylitis
-
Systemic Lupus Erythematosus
- Autoantibody to nuclear and ribosomal Antigens (dsDNA, SS-A or Ro, SS-B or La, Smith, DNA-Histone)
-
Drug-induced Lupus
- Autoantibody to nuclear Antigens (dsDNA, DNA-Histone)
-
Rheumatoid Arthritis
- Predisposition in patients with HLA-DR4 haplotypes (MHC Class 2)
- Autoantibody to nuclear Antigens (rheumatoid-associated nuclear Antigen, Ribonucleoprotein, DNA-Histone)
- Autoantibodies to IgG as well as IgM and IgA (Rheumatoid Factors)
- Autoantibody binding to Fc region of IgG results in Complement Activation and host tissue destruction
-
Scleroderma (Systemic Sclerosis, also part of CREST Syndrome)
- Autoantibody to nucleolar Antigens (nucleolar-specific RNA, centromere, Ribonucleoprotein, Scl-70/Topisomerase)
-
Polymyositis
- Autoantibody to nuclear Antigens (PM-Scl, Jo-1, Ribonucleoprotein)
-
Dermatomyositis
- Autoantibody to nuclear Antigens (Jo-1, Mi-2)
- Sjogren's Syndrome
XI. Associated Conditions: Neurologic Autoimmune Conditions
- Guillain-Barre Syndrome
-
Multiple Sclerosis
- Autoantibody to brain and spinal cord myelin Proteins
-
Myasthenia Gravis
- Autoantibody to Acetylcholine receptor on Muscle Cells
XII. Associated Conditions: Vascular Autoimmune Conditions
- Temporal Arteritis
- Anti-phospholipid Syndrome
- Granulomatosis with Polyangiitis (previously known as Wegener's Granulomatosis)
- Behcet's Syndrome
- Rheumatic Fever
XIII. Associated Conditions: Miscellaneous
XIV. References
- Mahmoudi (2014) Immunology Made Ridiculously Simple, MedMaster, Miami, FL, p. 32-40
- Zuber (2003) AAFP Board Review, Seattle