Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Curr Opin Rheumatol. 2025 Jan 1;37(1):51-63. doi: 10.1097/BOR.0000000000001035. Epub 2024 Aug 2.
Antinuclear autoantibodies represent a serological hallmark of systemic sclerosis (SSc), with anticentromere, antitopoisomerase-I, and anti-RNA polymerase III antibodies routinely assessed for diagnosis, clinical subset classification, and prognosis. In addition, an increasing number of autoantibodies have been demonstrated to play a pathogenic role by mediating different SSc manifestations. This review aims to give an overview on autoantibodies as putative biomarkers in SSc and discuss their possible pathogenic role as triggers of cell dysfunctions.
Over the years, different autoantibodies have been proposed as biomarkers aiding in diagnosis, disease subtype classification, disease progression prediction, organ involvement, as well as in understanding treatment response. Increasing literature also indicates functional autoantibodies as direct contributors to SSc pathogenesis by exerting agonistic or antagonistic activities on their specific cognate targets.
In SSc, search and validation of novel autoantibodies with higher diagnostic specificity and more accurate predictive values are increasingly needed for early diagnosis and specific follow-up, and to define the best therapeutic option according to different disease subsets. Moreover, since autoantibodies are also emerging as functional pathogenic players, a better unraveling of their possible pathomechanisms becomes essential to identify new targets and develop promising therapeutic agents able to neutralize their effects.
抗核抗体是系统性硬化症（SSc）的血清学标志，通常评估抗着丝点、抗拓扑异构酶 I 和抗 RNA 聚合酶 III 抗体用于诊断、临床亚型分类和预后。此外，越来越多的自身抗体已被证明通过介导不同的 SSc 表现发挥致病作用。这篇综述旨在概述自身抗体作为 SSc 中的潜在生物标志物，并讨论其可能的致病作用，作为细胞功能障碍的触发因素。
多年来，不同的自身抗体已被提出作为辅助诊断、疾病亚型分类、疾病进展预测、器官受累以及了解治疗反应的生物标志物。越来越多的文献还表明，功能性自身抗体作为 SSc 发病机制的直接贡献者，通过对其特定的同源靶标发挥激动或拮抗作用。
在 SSc 中，需要不断寻找和验证具有更高诊断特异性和更准确预测值的新型自身抗体，以实现早期诊断和特定随访，并根据不同疾病亚型确定最佳治疗选择。此外，由于自身抗体也作为功能性致病因子出现，因此必须更好地阐明其可能的发病机制，以确定新的靶点并开发有前途的能够中和其作用的治疗药物。
