Chavez Y, Garces J, Díaz R, Escobar M, Sanchez A, Buendía E, Múnera M
Medical Research Group (GINUMED) Universitary Corporation Rafael Nuñez, Centro Calle de la Soledad No. 5-70, Cartagena 130002, Colombia.
Catholic University of Manizales, Manizales, Av. Santander #No. 60, Manizales, Caldas 111321, Colombia.
Oxf Open Immunol. 2022 Dec 2;3(1):iqac009. doi: 10.1093/oxfimm/iqac009. eCollection 2022.
Wegener's granulomatosis is an autoimmune disease where autoantibodies target human autoantigen PR3, a serine protease locates on the neutrophil membrane. This disease affects blood small vessels and could be deadly. The origin of these autoantibodies is unknown, but infections have been implicated with autoimmune disease. In this study, we explored potential molecular mimicry between human PR3 and homologous pathogens through analysis. Thirteen serine proteases from human pathogens (, , sp., , , , , , , , and ) shared structural homology and amino acid sequence identity with human PR3. Epitope prediction found an only conserved epitope IVGG, located between residues 59-74. However, multiple alignments showed conserved regions that could be involved in cross-reactivity between human and pathogens serine proteases (90-98, 101-108, 162-169, 267 and 262 residues positions). In conclusion, this is the first report providing evidence about the existence of molecular mimicry between human and pathogens serine proteases, that could explain the origins of autoantibodies found in patients suffering from Wegener's granulomatosis.
韦格纳肉芽肿病是一种自身免疫性疾病，其中自身抗体靶向人类自身抗原PR3，一种位于中性粒细胞膜上的丝氨酸蛋白酶。这种疾病会影响血液中的小血管，可能会致命。这些自身抗体的起源尚不清楚，但感染与自身免疫性疾病有关。在本研究中，我们通过分析探索了人类PR3与同源病原体之间潜在的分子模拟。来自人类病原体（，，sp.，，，，，，，，和）的13种丝氨酸蛋白酶与人类PR3具有结构同源性和氨基酸序列同一性。表位预测发现一个仅有的保守表位IVGG，位于第59 - 74位残基之间。然而，多重比对显示了可能参与人类和病原体丝氨酸蛋白酶之间交叉反应的保守区域（第90 - 98、101 - 108、162 - 169、267和262位残基位置）。总之，这是第一份提供证据证明人类和病原体丝氨酸蛋白酶之间存在分子模拟的报告，这可以解释在韦格纳肉芽肿病患者中发现的自身抗体的起源。
