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

Abstract

One of the probable hypotheses for the onset of autoimmunity is molecular mimicry. This study aimed to determine the HLA-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 (TPO) based on the presence of HLA risk alleles. HLA-DRB1/-DQB1 genotyping was performed in 100 HT patients and 330 ethnically matched healthy controls to determine the predisposing/protective HLA alleles for HT disease in our population. Then, insilico analysis was carried out to examine the sequence homology between epitopes derived from autoantigens and four potentially relevant pathogens and their binding capacity for HLA risk alleles based on peptide docking analysis. We identi ed HLA-DRB1*03:01, *04:02, *04:05 and *11:04 as predisposing alleles and DRB1*13:01 as potentially predictive allele for HT disease. Also, DRB1*11:04 ~ DQB1*03:01 (Pc = 0.002, OR:3.97) and DRB1*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 in discrimination of 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 herpes virus and sequence 151-199 of TPO with remarkable binding capacity to HLA-DRB1*03:01 allele. Our ndings indicate the increased risk of developing HT in those individual carrying HLA risk alleles which can also be related to herpes virus infection.