THE HLA GENE COMPLEX IN THYROID AUTOIMMUNITY: FROM EPIDEMIOLOGY TO ETIOLOGY

摘要: The autoimmune thyroid diseases (AITD) comprise a cadre of complex whose underlying pathoetiology stems from genetic-environmental interaction, between susceptibility genes (e.g. CTLA-4, HLA-DR, thyroglobulin) and environmental triggers dietary iodine), that orchestrates the initiation an response to antigens, leading onset disease. Abundant epidemiological data, including family twin studies, point strong genetic influence on development AITD. Several AITD have been identified, with HLA genes, in particular, appearing be major importance. Early studies showed association HLA-DR3 Graves' disease (GD) Caucasians. More recently, importance amino acid substitution at position 74 DR beta 1 chain (DRb1-Arg74), disease, has shown. Furthermore, there is increasing evidence for interaction thyroglobulin variants DRb1-Arg74 conferring risk GD. Mechanistically, presence arginine elicits significant structural change peptide binding pocket potentially affecting pathogenic thyroidal peptides. Future therapeutic interventions may attempt exploit this new bolus knowledge by endeavoring block or modulate presentation HLA-DR.