Gkoutzourelas Athanasios, Barmakoudi Maria, Bogdanos Dimitrios P
Department of Rheumatology and Clinical Immunology, Faculty of Medicine, University of Thessaly, Larissa, Greece.
Mediterr J Rheumatol. 2020 Mar 31;31(1):50-70. doi: 10.31138/mjr.31.1.50. eCollection 2020 Mar.
A recent bioinformatic analysis revealing dominant B cell epitopes of systemic sclerosis-specific autoantibodies, including anti-centromere B, anti-topoisomerase I and anti-fibrillarin, has demonstrated the existence of several in silico antigenic mimics of pathogens that could act as triggers of the respective dominant autoepitopes. Based on those findings, the aim of the present study was to use a more comprehensive bioinformatic analysis. We demonstrated the presence of a plethora of novel microbial mimics, unnoticed by the studies so far conducted, which share remarkable amino acid similarities with the respective autoantigenic epitopes. This bioinformatic approach coupled by in vitro testing of the homologous self/non-self-mimics in serum samples from patients with systemic sclerosis may provide novel evidence of immunological cross-reactivity, implicating currently ignored or overlooked pathogens, which may indeed play a role in the induction of SSc-specific autoantibodies and assist efforts to understand the pathogenesis of this enigmatic disease.
最近一项生物信息学分析揭示了系统性硬化症特异性自身抗体（包括抗着丝粒B抗体、抗拓扑异构酶I抗体和抗核仁纤维蛋白抗体）的主要B细胞表位，证明存在几种病原体的计算机模拟抗原，它们可能是各自主要自身表位的触发因素。基于这些发现，本研究的目的是进行更全面的生物信息学分析。我们证明了存在大量迄今为止的研究所未发现的新型微生物模拟物，它们与各自的自身抗原表位具有显著的氨基酸相似性。这种生物信息学方法，再结合对系统性硬化症患者血清样本中的同源自身/非自身模拟物进行体外检测，可能会提供免疫交叉反应性的新证据，涉及目前被忽视或未被重视的病原体，这些病原体可能确实在系统性硬化症特异性自身抗体的诱导中起作用，并有助于努力理解这种神秘疾病的发病机制。
