Table 1.
Summary of major susceptibility genes for AITD and their point of action in the immunoregulatory pathway (central tolerance vs peripheral tolerance vs co-stimulatory signals for proper antigen presentation), chromosomal location, and associated autoimmune diseases (may vary by ethnicity; see references).
Pathway/ Mechanism | GenGene | Chromosome | Associated Autoimmune Diseases | Ref. |
---|---|---|---|---|
Central Tolerance | TSHR | 14q31 | GD | [16, 17] |
Peripheral Tolerance | FOXP3 | Xp11 | GD, HT IPEX T1D RA PBC Psoriasis, Vitiligo Autoimmune Hemolytic Anemia Autoimmune Cytopenia Autoimmune Hepatitis |
[33, 34, 36, 37, 40] |
Peripheral Tolerance | IL-2Rα/ CD25 | 10p15 | GD T1D MS |
[41, 45] |
Co-stimulation (APC and T cell activation) | CD40 | 20q11 | GD SLE RA MS Behcet's disease IBD |
[50, 55-58, 66-68, 113] |
Co-stimulation (T cell activation) | CTLA-4 | 2q33 | GD, HT T1D Autoimmune Addison's Disease SLE RA MS PBC IBD Celiac disease Sjogren's disease Systemic sclerosis Myasthenia gravis |
[86, 114-120] |
Co-stimulation (T cell activation) | PTPN22/LYP | 1p13 | GD, HT T1D SLE RA |
[121-124] |
Co-stimulation (B Cell Activation) | FCRL3 | 1q21-22 | GD, HT SLE RA MS Behcet's disease NMO |
[125-128] |
Antigen Presentation (T cell activation) | HLA | 6p21 | GD, HT T1D SLE RA MS Celiac disease Behcet's disease Myasthenia gravis |
[129, 130]* |
see references for complete list of HLA-associated autoimmune diseases
Abbreviations: TSHR (thyrotropin receptor), FOXP3 (forkhead box P3), CTLA-4 (cytotoxic T-lymphocyte-associated molecule-4), PTPN22 (protein tyrosine phosphatase nonreceptor type-22), LYP (lymphoid tyrosine phosphatase), FCRL3(Fc receptor-like 3), Graves' disease (GD), Hashimoto's thyroiditis (HT), immune dysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX), type I diabetes mellitus (T1D), rheumatoid arthritis (RA), primary biliary cirrhosis (PBC), systemic lupus erythematosus (SLE), multiple sclerosis (MS), inflammatory bowel disease (IBD), neuromyelitis optica (NMO)