Determination of HLA class II risk alleles and prediction of self/non-self-epitopes contributing Hashimoto ’s thyroiditis in a group of Iranian patients

This study aimed to determine theHLA-II risk alleles for developing Hashimoto ’s thyroiditis (HT) in order to analyze the molecular homology between candidate pathogen-derived epitopes and potentially self-antigens (thyroid peroxidase, TPO) based on the presence ofHLA risk alleles.HLA-DRB1/-DQB1 genotyping was performed in 100 HT patients and 330 ethnically matched healthy controls to determine the predisposing/protective alleles for HT disease. Then, in silico analysis was conducted to examine the sequence homology between epitopes derived from autoantigens and four potentially relevant pathogens and their binding capacities toHLA risk alleles based on peptide docking analysis. We identifiedHLA-DRB1*03:01, *04:02, *04:05, and *11:04 as predisposing alleles andDRB1*13:01 as a potentially predictive allele for HT disease. Also,DRB1*11:04 ~ DQB1*03:01 (Pc  = 0.002; OR, 3.97) andDRB1*03:01 ~ DQB1*02:01 (Pc  = 0.004; OR, 2.24) haplotypes conferred a predisposing role for HT. Based on logistic regression analysis, carrying risk alleles increased the risk of HT development 4.5 times in our population (P = 7.09E-10). Also, ROC curve analysis revealed a high predictive power of those risk alleles f or discrimination of the susceptible from healthy individuals (AUC, 0.70; P = 6.6E-10). Analysis of peptide sequence homology between epitopes of TPO and epitopes derived from four candidate microorganisms revealed a homology between envelop glycoprotein D of herp...
Source: Immunogenetics - Category: Genetics & Stem Cells Source Type: research