Immunoglobulins G from Systemic Sclerosis Patients Modify the Molecular Signatures of Endothelial Cells

Antinuclear antibodies (ANA) are powerful biomarkers in systemic sclerosis (SSc). Functional antibodies (FA) might be implicated in the vasculopathy, in which endothelial cells (EC) are key players. We aimed to explore the effect of purified IgG from SSc patients on omics signatures of EC and examine the influence of ANA serotypes or FA. EC were cultured in the presence of purified IgG from SSc patients, systemic lupus erythematosus patients (SLE) or healthy controls (HC). EC omics profiles were analyzed by liquid chromatography with tandem mass spectrometry (LC-MS/MS) and RNA sequencing. EC proteome induced by IgG from SSc patients was confirmed with an external validation cohort. In the derivation cohort, principal component analysis (PCA) using proteomics data showed 3 distinct groups of subjects: a first one including mostly anti-topoisomerase-I positive patients (ATA+), a second one including mostly anti-centromere positive patients (ACA+) and a third group comprising anti-RNA polymerase-III positive patients (ARA+), SLE and HC. In transcriptomics, PCA distinguished one group composed by 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, FA impact was minimal. Quantitative proteomics measured the most discriminant proteins in EC exposed to purified IgG. Purified IgG from SSc patients modify EC proteome and transcriptome according to ANA serotypes. IgG from ATA+ patients induced distinct EC proteomic profiles.