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

Mar 24, 2025

Experts: Aurélien Chepy,Solange Vivier,Fabrice Bray,Clément Chauvet,Alain Lescoat,Abderrahmane Elhannani,Martin Figeac,Lucile Guilbert,Frédéric Leprêtre,Louisa Bourel,Eric Hachulla,Christian Rolando,Valérie Lecureur,Sylvain Dubucquoi,David Launay,Vincent Sobanski

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.

© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.

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ABOUT THE EXPERTS

Aurélien Chepy,Solange Vivier,Fabrice Bray,Clément Chauvet,Alain Lescoat,Abderrahmane Elhannani,Martin Figeac,Lucile Guilbert,Frédéric Leprêtre,Louisa Bourel,Eric Hachulla,Christian Rolando,Valérie Lecureur,Sylvain Dubucquoi,David Launay,Vincent Sobanski

Aurélien Chepy

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.

Solange Vivier

Univ. Lille, Inserm, CHU Lille, U1286 – INFINITE – Institute for Translational Research in Inflammation, Lille, France.

Fabrice Bray

Univ. Lille, CNRS, USR 3290 – MSAP – Miniaturisation pour la Synthèse, l’Analyse et la Protéomique, Lille, France.

Clément Chauvet

Univ. Lille, Inserm, CHU Lille, U1286 – INFINITE – Institute for Translational Research in Inflammation, Lille, France.

Alain Lescoat

Service de Médecine Interne et Immunologie Clinique, CHU Rennes, Université Rennes, Rennes, France.

Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) – UMR_S 1085, Rennes, France.

Abderrahmane Elhannani

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.

Martin Figeac

Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 – UAR 2014 – PLBS, Lille, France.

Lucile Guilbert

Univ. Lille, Inserm, CHU Lille, U1286 – INFINITE – Institute for Translational Research in Inflammation, Lille, France.

CHU Lille, Institut d’Immunologie, Lille, France.

Frédéric Leprêtre

Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US 41 – UAR 2014 – PLBS, Lille, France.

Louisa Bourel

Univ. Lille, Inserm, CHU Lille, U1286 – INFINITE – Institute for Translational Research in Inflammation, Lille, France.

Eric Hachulla

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.

Christian Rolando

Univ. Lille, CNRS, USR 3290 – MSAP – Miniaturisation pour la Synthèse, l’Analyse et la Protéomique, Lille, France.

Valérie Lecureur

Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) – UMR_S 1085, Rennes, France.

Sylvain Dubucquoi

Univ. Lille, Inserm, CHU Lille, U1286 – INFINITE – Institute for Translational Research in Inflammation, Lille, France.

CHU Lille, Institut d’Immunologie, Lille, France.

David Launay

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.

Vincent Sobanski

Univ. Lille, Inserm, CHU Lille, U1286 – INFINITE – Institute for Translational Research in Inflammation, Lille, France vincent.sobanski@univ-lille.fr.

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.

Institut Universitaire de France (IUF), Paris, France.