03286nab a2200373 i 4500 publ24510 20220610120657.0 220610s2022 hu o 0|| Angol d 2326-5191 10.1002/art.42243 doi 32869486 mtmt SZTE Publicatio Repozitórium hun Angol Foulquier Nathan Machine learning identifies a common signature for anti-SSA/Ro60 antibody expression across autoimmune diseases [elektronikus dokumentum] / Foulquier Nathan 2022 Terjedelem: 31 p.-Azonosító: 42243 ARTHRITIS & RHEUMATOLOGY Anti-Ro autoantibodies are among the most frequently detected extractable nuclear antigen autoantibodies, mainly associated with primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and undifferentiated connective tissue disease (UCTD). Is there a common signature to all patients expressing anti-Ro60 autoantibodies regardless of their disease phenotype?Using high-throughput multi-omics data collected within the cross-sectional cohort from the PRECISESADS IMI project (genetic, epigenomic, transcriptomic, combined with flow cytometric data, multiplexed cytokines, classical serology and clinical data), we assessed by machine learning the integrated molecular profiling of 520 anti-Ro60-positive (anti-Ro60+ ) compared to 511 anti-Ro60-negative (anti-Ro60- ) patients with pSS, SLE and UCTD, and 279 healthy controls (HCs).The selected features for RNA-Seq, DNA methylation and GWAS data allowed a clear separation between anti-Ro60+ and anti-Ro60- patients. The different features selected by machine learning from the anti-Ro60+ patients constitute specific signatures when compared to anti-Ro60- patients and HCs. Remarkably, the transcript z-score of three genes (ATP10A, MX1 and PARP14), presenting an overexpression associated with a hypomethylation and genetic variation, and independently identified by the Boruta algorithm, was clearly higher in anti-Ro60+ patients compared to anti-Ro60- patients in all the diseases. We demonstrate that these signatures, enriched in interferon stimulated genes, were also found in anti-Ro60+ patients with rheumatoid arthritis and systemic sclerosis and remained stable over time and not influenced by treatment.Anti-Ro60+ patients present a specific inflammatory signature regardless of their disease suggesting that a dual therapeutic approach targeting both Ro-associated RNAs and anti-Ro60 autoantibodies should be considered. Immunológia Le Dantec Christelle aut Bettacchioli Eleonore aut Jamin Christophe aut Alarcón-Riquelme Marta Eugenia aut Pers Jacques-Olivier aut Kollaborációs szervezet: PRECISESADS Clinical Consortium aut Kollaborációs szervezet PRECISESADS Flow Cytometry Consortium aut Kovács László aut Balog Attila aut Deák Magdolna aut Bocskai Márta aut Dulic Sonja aut Kádár Gabriella aut http://publicatio.bibl.u-szeged.hu/24510/1/FoulquierArthritisRheumatology2022.pdf Dokumentum-elérés