Frommer L, et al. - Researchers conducted this immunogenetic study to examine the impact of amino acid polymorphisms on the peptide-binding interactions within human leucocyte antigen (HLA) class II and its correlation with polyglandular autoimmunity (AP). Five hundred eighty-seven patients with AP, autoimmune thyroid disease (AITD), type 1 diabetes (T1D), and healthy unrelated controls were typed for HLA class II. In all individuals, amino acids within the peptide binding cleft that are encoded by HLA class II exon 2 were listed for all codon positions. According to results, the Monte Carlo exact Fisher test showed marked variations in all 3 loci, DQA1, DQB1, and DRB1 between AP and both AITD and controls, as well as between AP type II (Addison’s disease as a major endocrine component) and AP type III (T1D + AITD). In addition, differences were observed between AP and T1D pertaining to the DRB1 allele. Amino acid polymorphisms within HLA class II exon 2 mediate the risk of AP and distinguish  between thyroid and polyglandular autoimmunity.