Chepy Aurélien, Vivier Solange, Bray Fabrice, Chauvet Clément, Lescoat Alain, Elhannani Abderrahmane, Figeac Martin, Guilbert Lucile, Leprêtre Frédéric, Bourel Louisa, Hachulla Eric, Rolando Christian, Lecureur Valérie, Dubucquoi Sylvain, Launay David, Sobanski Vincent
Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France.
CHU Lille, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-Immunes et Auto-Inflammatoires Rares du Nord, Nord-Ouest, Méditerranée et Guadeloupe (CeRAINOM), Lille, France.
RMD Open. 2025 Mar 23;11(1):e004290. doi: 10.1136/rmdopen-2024-004290.
Antinuclear antibodies (ANA) are powerful biomarkers in systemic sclerosis (SSc). Functional antibodies (FA) might be implicated in vasculopathy, in which endothelial cells (EC) are key players. We aimed to explore the effect of purified IgG from patients with SSc on omics signatures of EC and examine the influence of ANA serotypes and FA.
EC were cultured in the presence of purified IgG from patients with SSc, patients with systemic lupus erythematosus (SLE) or healthy controls (HC). EC omics profiles were analysed by liquid chromatography with tandem mass spectrometry (LC-MS/MS) and RNA sequencing. EC proteome induced by IgG from patients with SSc was confirmed with an external validation cohort.
In the derivation cohort, principal component analysis (PCA) using proteomics data showed three distinct groups of subjects: a first one including mostly anti-topoisomerase-I positive patients (ATA+), a second one including mostly anti-centromere positive patients and a third group comprising anti-RNA polymerase-III positive patients, SLE and HC. In transcriptomics, PCA distinguished one group composed of ATA+patients only from a second group mixing ATA+patients with other individuals. The validation cohort confirmed the existence of two groups of distinct EC proteome profiles and clinical severity in ATA+patients. In both SSc cohorts, no association between FA presence and proteomic profiles was observed. Quantitative proteomics measured the most discriminant proteins in EC exposed to purified IgG.
Purified IgG from patients with SSc can modify EC proteome and transcriptome. The observed changes closely associate with ANA serotype.
抗核抗体（ANA）是系统性硬化症（SSc）中强大的生物标志物。功能性抗体（FA）可能与血管病变有关，其中内皮细胞（EC）是关键因素。我们旨在探讨SSc患者纯化IgG对EC组学特征的影响，并研究ANA血清型和FA的作用。
将EC与SSc患者、系统性红斑狼疮（SLE）患者或健康对照（HC）的纯化IgG一起培养。通过液相色谱串联质谱（LC-MS/MS）和RNA测序分析EC的组学特征。用外部验证队列证实了SSc患者IgG诱导的EC蛋白质组。
在衍生队列中，使用蛋白质组学数据进行的主成分分析（PCA）显示出三组不同的受试者：第一组主要包括抗拓扑异构酶-I阳性患者（ATA+），第二组主要包括抗着丝点阳性患者，第三组包括抗RNA聚合酶-III阳性患者、SLE患者和HC。在转录组学中，PCA将仅由ATA+患者组成的一组与将ATA+患者与其他个体混合的第二组区分开来。验证队列证实了ATA+患者中存在两组不同的EC蛋白质组特征和临床严重程度。在两个SSc队列中，均未观察到FA的存在与蛋白质组特征之间的关联。定量蛋白质组学测定了暴露于纯化IgG的EC中最具鉴别力的蛋白质。
SSc患者的纯化IgG可改变EC蛋白质组和转录组。观察到的变化与ANA血清型密切相关。
