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 (thyroid peroxidase, 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 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 to HLA risk alleles based on peptide docking analysis. We identified HLA-DRB1*03:01, *04:02, *04:05, and *11:04 as predisposing alleles and DRB1*13:01 as a 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 for 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 herpes virus and sequence 151–199 of TPO with remarkable binding capacity to HLA-DRB1*03:01 allele. Our findings indicate the increased risk of developing HT in those individuals carrying HLA risk alleles which can also be related to herpes virus infection.

自身免疫发生的可能假设之一是分子拟态。本研究旨在确定发展桥本甲状腺炎 (HT) 的HLA-II风险等位基因，以便根据HLA风险等位基因的存在分析候选病原体衍生表位与潜在自身抗原（甲状腺过氧化物酶，TPO）之间的分子同源性。对 100 名 HT 患者和 330 名种族匹配的健康对照进行HLA-DRB1/-DQB1基因分型，以确定 HT 疾病的诱发/保护性等位基因。然后，进行计算机分析，以基于肽对接分析检查源自自身抗原和四种潜在相关病原体的表位之间的序列同源性及其与HLA风险等位基因的结合能力。我们确定HLA-DRB1*03:01、*04:02、*04:05和 * 11:04为易感等位基因，DRB1*13:01为 HT 疾病的潜在预测等位基因。此外，DRB1*11:04  ~  DQB1*03:01 (Pc = 0.002; OR, 3.97) 和DRB1*03:01  ~  DQB1*02:01 (Pc = 0.004; OR, 2.24) 单倍型赋予 HT 的易感作用。根据逻辑回归分析，携带风险等位基因会使我们人群患 HT 的风险增加 4.5 倍 (P = 7.09E-10)。此外，ROC 曲线分析显示这些风险等位基因对于区分易感者和健康个体具有很高的预测能力（AUC，0.70；P = 6.6E-10）。对 TPO 表位与来自四种候选微生物的表位之间的肽序列同源性分析揭示了疱疹病毒的包膜糖蛋白 D 与 TPO 序列 151-199 之间的同源性，对HLA-DRB1*03:01等位基因具有显着的结合能力。我们的研究结果表明，携带HLA风险等位基因的个体患 HT 的风险增加，这也可能与疱疹病毒感染有关。