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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.<\/jats:p>","DOI":"10.3389\/fimmu.2022.904631","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T04:51:35Z","timestamp":1656478295000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Effects of Immunoglobulins G From Systemic Sclerosis Patients in Normal Dermal Fibroblasts: A Multi-Omics Study"],"prefix":"10.3389","volume":"13","author":[{"given":"Aur\u00e9lien","family":"Chepy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solange","family":"Vivier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Bray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Ternynck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pascal","family":"Meneboo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Figeac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Filiot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucile","family":"Guilbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manel","family":"Jendoubi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Rolando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Launay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Dubucquoi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillemette","family":"Marot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Sobanski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1685\u221299","DOI":"10.1016\/S0140-6736(17)30933-9","article-title":"Systemic Sclerosis","volume":"390","author":"Denton","year":"2017","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.revmed.2016.02.016","article-title":"Role of B Cells in the Pathogenesis of Systemic Sclerosis","volume":"38","author":"Sanges","year":"2017","journal-title":"Rev Med Interne F\u00e9vr"},{"key":"B3","doi-asserted-by":"publisher","first-page":"40\u221251","DOI":"10.1007\/s12016-018-8718-8","article-title":"Antinuclear Antibodies in Systemic Sclerosis: An Update","volume":"58","author":"Stochmal","year":"2020","journal-title":"Clin Rev Allergy Immunol F\u00e9vr"},{"key":"B4","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1186\/s13075-018-1689-6","article-title":"Immune Complexes Containing Scleroderma-Specific Autoantibodies Induce a Profibrotic and Proinflammatory Phenotype in Skin Fibroblasts","volume":"20","author":"Raschi","year":"2018","journal-title":"Arthritis Res Ther 29"},{"key":"B5","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1186\/s13075-020-02360-3","article-title":"Scleroderma-Specific Autoantibodies Embedded in Immune Complexes Mediate Endothelial Damage: An Early Event in the Pathogenesis of Systemic Sclerosis","volume":"22","author":"Raschi","year":"2020","journal-title":"Arthritis Res Ther 9"},{"key":"B6","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/s13075-019-1931-x","article-title":"Antibodies Against Specific Extractable Nuclear Antigens (ENAs) as Diagnostic and Prognostic Tools and Inducers of a Profibrotic Phenotype in Cultured Human Skin Fibroblasts: Are They Functional? 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