Maldonado-Catala Pablo, Gouripeddi Ram, Schlesinger Naomi, Facelli Julio C
Department of Biomedical Informatics and Utah Clinical and Translational Science Institute.
Division of Rheumatology, The University of Utah.
Immunoinformatics (Amst). 2025 Jun;18. doi: 10.1016/j.immuno.2025.100050. Epub 2025 Mar 13.
Molecular mimicry is one mechanism by which an infectious agent may trigger an autoimmune disease in a human subject and occurs when foreign- and self-peptides contain similar epitopes that activate an autoimmune response in a susceptible individual. Here, we employ a scalable in-silico approach, to identify 861 pairs of known SARS-CoV-2 and autoimmune disease epitopes, out of more than one billion possible pairs. These SARS-CoV-2 epitopes show 1) sequence homology to human autoimmune disorder epitopes, 2) empirical binding data that predict that they bind the same major histocompatibility complex (MHC) molecule and 3) exhibit high empirical immunogenicity. Analysis of these epitope pairs reveals an association between autoimmune disorders, such as type 1 diabetes, autoimmune uveitis, ankylosing spondylitis, and SARS-CoV-2 infection. These associations are consistent with those reported in the literature from the analysis of clinical records.
分子模拟是一种感染因子可能在人类受试者中引发自身免疫性疾病的机制,当外源肽和自身肽包含相似的表位,从而在易感个体中激活自身免疫反应时就会发生。在此,我们采用一种可扩展的计算机模拟方法,从超过十亿种可能的组合中,识别出861对已知的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)和自身免疫性疾病表位。这些SARS-CoV-2表位显示出:1)与人类自身免疫性疾病表位的序列同源性;2)预测它们能结合相同主要组织相容性复合体(MHC)分子的实验性结合数据;3)具有高实验性免疫原性。对这些表位对的分析揭示了1型糖尿病、自身免疫性葡萄膜炎、强直性脊柱炎等自身免疫性疾病与SARS-CoV-2感染之间的关联。这些关联与文献中通过临床记录分析所报告的关联一致。