Title :

Effects of Immunoglobulins G From Systemic Sclerosis Patients in Normal Dermal Fibroblasts: A Multi-Omics Study

Author(s) :

Chepy, Aurelien [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Service de médecine interne [Lille]
Vivier, Solange [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Bray, Fabrice [Auteur]
Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 [MSAP]
Ternynck, Camille [Auteur]
Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Meneboo, Jean-Pascal [Auteur]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
Figeac, Martin [Auteur]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
Filiot, Alexandre [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Guilbert, Lucile [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Institut d'Immunologie [CHRU Lille]
Jendoubi, Manel [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Rolando, Christian [Auteur]
Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 [MSAP]
Launay, David [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Dubucquoi, Sylvain [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Service de médecine interne [Lille]
Briend, Guillemette [Auteur]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
MOdel for Data Analysis and Learning [MODAL]
Sobanski, Vincent [Auteur]
Service de médecine interne [Lille]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Institut universitaire de France [IUF]

Journal title :

Frontiers in Immunology

Pages :

904631

Publisher :

Frontiers

Publication date :

2022-06-29

ISSN :

1664-3224

English keyword(s) :

systemic sclerosis
multi-omics analysis
autoantibodies
proteomics
transcriptomics

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Autoantibodies (Aabs) are frequent in systemic sclerosis (SSc). Although recognized as potent biomarkers, their pathogenic role is debated. This study explored the effect of purified immunoglobulin G (IgG) from SSc patients ...
Show more >Autoantibodies (Aabs) are frequent in systemic sclerosis (SSc). Although recognized as potent biomarkers, their pathogenic role is debated. This study explored the effect of purified immunoglobulin G (IgG) from SSc patients on protein and mRNA expression of dermal fibroblasts (FBs) using an innovative multi-omics approach. Dermal FBs were cultured in the presence of sera or purified IgG from patients with diffuse cutaneous SSc (dcSSc), limited cutaneous SSc or healthy controls (HCs). The FB proteome and transcriptome were explored using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and microarray assays, respectively. Proteomic analysis identified 3,310 proteins. SSc sera and purified IgG induced singular protein profile patterns. These FB proteome changes depended on the Aab serotype, with a singular effect observed with purified IgG from anti-topoisomerase-I autoantibody (ATA) positive patients compared to HC or other SSc serotypes. IgG from ATA positive SSc patients induced enrichment in proteins involved in focal adhesion, cadherin binding, cytosolic part, or lytic vacuole. Multi-omics analysis was performed in two ways: first by restricting the analysis of the transcriptomic data to differentially expressed proteins; and secondly, by performing a global statistical analysis integrating proteomics and transcriptomics. Transcriptomic analysis distinguished 764 differentially expressed genes and revealed that IgG from dcSSc can induce extracellular matrix (ECM) remodeling changes in gene expression profiles in FB. Global statistical analysis integrating proteomics and transcriptomics confirmed that IgG from SSc can induce ECM remodeling and activate FB profiles. This effect depended on the serotype of the patient, suggesting that SSc Aab might play a pathogenic role in some SSc subsets.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Laboratoire Paul Painlevé - UMR 8524

Source :

Harvested from HAL