Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
Curr Opin Rheumatol. 2021 Nov 1;33(6):486-494. doi: 10.1097/BOR.0000000000000834.
Autoantibodies are hallmark findings in systemic sclerosis (SSc), often present prior to disease onset. Clinical diagnosis and prognosis of SSc have long relied on the antitopoisomerase - anticentromere - anti-RNA polymerase antibody trichotomy. However, many more autoantibodies found in SSc are being actively investigated for insights into triggering events, mechanisms of tolerance break, and connections to tissue damage. This review examines recent studies on SSc autoantibodies and the early events that lead to their development.
Recent work has elucidated potential connections between human cytomegalovirus infection, silicone breast implants, and malignancy to SSc autoantibody development. At the level of the dendritic cell:T cell interaction, where tolerance is broken, new studies identified shared motifs in the peptide-binding domains of SSc-associated human leukocyte antigen alleles. Immunological analysis of SSc patient B cells has uncovered several anomalies in the regulatory capacities of SSc naïve and memory B cell populations. Expanding efforts to uncover new SSc autoantibodies revealed anti-CXCL4, anticollagen V, and other autoantibodies as potential players in disease pathogenesis.
Further research into the role of autoantibodies in SSc development may uncover new mechanism-guided therapeutic targets. In addition, a better understanding of autoantibody associations with SSc disease outcomes will improve clinical care.
自身抗体是系统性硬化症（SSc）的标志性发现，通常在疾病发作前就已存在。SSc 的临床诊断和预后长期以来一直依赖于抗拓扑异构酶-抗着丝粒-抗 RNA 聚合酶抗体三分法。然而，人们正在积极研究 SSc 中发现的许多其他自身抗体，以深入了解触发事件、耐受破坏的机制以及与组织损伤的关系。这篇综述探讨了 SSc 自身抗体及其导致自身抗体产生的早期事件的最新研究进展。
最近的研究阐明了人类巨细胞病毒感染、硅酮乳房植入物和恶性肿瘤与 SSc 自身抗体发展之间的潜在联系。在树突状细胞与 T 细胞相互作用的水平上，即耐受被打破的水平上，新的研究确定了与 SSc 相关的人类白细胞抗原等位基因肽结合结构域中的共享基序。对 SSc 患者 B 细胞的免疫分析揭示了 SSc 幼稚和记忆 B 细胞群体在调节能力方面的几个异常。扩大发现新的 SSc 自身抗体的努力揭示了抗 CXCL4、抗胶原 V 等自身抗体可能是疾病发病机制中的潜在参与者。
进一步研究自身抗体在 SSc 发病机制中的作用可能会发现新的机制导向治疗靶点。此外，更好地了解自身抗体与 SSc 疾病结局的关联将改善临床护理。
