Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Department of Pulmonology, Cologne Merheim Hospital, Kliniken der Stadt Köln gGmbH, Witten/Herdecke University, Cologne, Germany.
Front Immunol. 2023 Jan 4;13:1045523. doi: 10.3389/fimmu.2022.1045523. eCollection 2022.
Systemic sclerosis (SSc) belongs to the group of connective tissue diseases and is associated with the occurrence of disease-specific autoantibodies. Although it is still controversial whether these antibodies contribute to pathogenesis, there are new insights into the development of these specific antibodies and their possible pathophysiological properties. Interestingly, they are associated with specific clinical manifestations, but for some rarer antibodies this association is not fully clarified. The aim of this study is a comprehensive analysis of the serum autoantibody status in patients with SSc followed by correlation analyses of autoantibodies with the clinical course of the disease.
Serum from SSc patients was analyzed using a line blot (EUROLINE, EUROIMMUN AG) for SSc-related autoantibodies. Autoantibodies to centromere, Topo-1, antimitochondrial antibodies (AMA) M2 subunit, angiotensin II type 1 receptors (ATR) and endothelin-1 type-A-receptors (ETR) were also determined by ELISA. We formed immunological clusters and used principal components analysis (PCA) to assign specific clinical characteristics to these clusters.
A total of 372 SSc patients were included. 95.3% of the patients were antinuclear antibody positive and in 333 patients at least one SSc specific antibody could be detected. Four immunological clusters could be found by PCA. Centromere, Topo-1 and RP3 all formed own clusters, which are associated with distinct clinical phenotypes. We found that patients with an inverted phenotype, such as limited cutaneous SSc patients within the Topo-1 cluster show an increased risk for interstital lung disease compared to ACA positive patients. Anti-ATR and anti-ETR autoantibodies were measured in 176 SSc patients; no association with SSc disease manifestation was found. SSc patients with AMA-M2 antibodies showed an increased risk of cardiovascular events.
In our in large cluster analysis, which included an extended autoantibody profile, we were able to show that serologic status of SSc patients provides important clues to disease manifestation, co-morbidities and complications. Line blot was a reliable technique to detect autoantibodies in SSc and detected rarer autoantibodies in 42% of our patients.
系统性硬化症（SSc）属于结缔组织疾病，与疾病特异性自身抗体的发生有关。尽管这些抗体是否有助于发病机制仍存在争议，但对这些特定抗体的发展及其可能的病理生理特性有了新的认识。有趣的是，它们与特定的临床表现有关，但对于一些罕见的抗体，这种关联尚未完全阐明。本研究的目的是全面分析 SSc 患者的血清自身抗体状态，并对自身抗体与疾病临床过程进行相关性分析。
使用线印迹（EUROLINE，EUROIMMUN AG）分析 SSc 患者的血清，以检测 SSc 相关自身抗体。还通过 ELISA 测定着丝粒、拓扑异构酶 1、抗线粒体抗体（AMA）M2 亚单位、血管紧张素 II 型 1 受体（ATR）和内皮素 1 型-A 受体（ETR）自身抗体。我们形成免疫群集，并使用主成分分析（PCA）将特定的临床特征分配给这些群集。
共纳入 372 例 SSc 患者。95.3%的患者抗核抗体阳性，333 例患者至少检测到一种 SSc 特异性抗体。通过 PCA 发现了 4 个免疫群集。着丝粒、拓扑异构酶 1 和 RP3 均形成自己的群集，与独特的临床表型相关。我们发现，在拓扑异构酶 1 群集内，如局限性皮肤型 SSc 患者的倒置表型，与 ACA 阳性患者相比，间质性肺病的风险增加。在 176 例 SSc 患者中测量了抗 ATR 和抗 ETR 自身抗体；与 SSc 疾病表现无关联。AMA-M2 抗体阳性的 SSc 患者发生心血管事件的风险增加。
在我们的大型聚类分析中，包括了扩展的自身抗体谱，我们能够表明 SSc 患者的血清状态为疾病表现、合并症和并发症提供了重要线索。线印迹是检测 SSc 自身抗体的可靠技术，在我们的 42%患者中检测到了罕见的自身抗体。
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