Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients. Issue 9 (19th June 2020)

• Record Type: Journal Article
• Authors: Beretta, Lorenzo; Barturen, Guillermo; Vigone, Barbara; Bellocchi, Chiara; Hunzelmann, Nicolas; De Langhe, Ellen; Cervera, Ricard; Gerosa, Maria; Kovács, László; Ortega Castro, Rafaela; Almeida, Isabel; Cornec, Divi; Chizzolini, Carlo; Pers, Jacques-Olivier; Makowska, Zuzanna; Lesche, Ralf; Kerick, Martin; Alarcón-Riquelme, Marta Eugenia; Martin, Javier
• Other Names: author non-byline.; Belz Doreen author non-byline.; Collantes-Estevez Eduardo author non-byline.; Ingegnoli Francesca author non-byline.; Gómez Yolanda Jimenez author non-byline.; Pedrera Chary Lopez author non-byline.; Lories Rik author non-byline.; Montanelli Gaia author non-byline.; Piantoni Silvia author non-byline.; Pinto Ignasi Rodriguez author non-byline.; Vasconcelos Carlos author non-byline.; author non-byline.; Jamin Christophe author non-byline.; Marañón Concepción author non-byline.; Lann Lucas Le author non-byline.; Simon Quentin author non-byline.; Rouvière Bénédicte author non-byline.; Varela Nieves author non-byline.; Muchmore Brian author non-byline.; Dufour Aleksandra author non-byline.; Alvarez Montserrat author non-byline.; Cremer Jonathan author non-byline.; Barbarroja Nuria author non-byline.; Gerl Velia author non-byline.; Khodadadi Laleh author non-byline.; Cheng Qingyu author non-byline.; Buttgereit Anne author non-byline.; Groof Aurélie De author non-byline.; Ducreux Julie author non-byline.; Trombetta Elena author non-byline.; Li Tianlu author non-byline.; Alvarez-Errico Damiana author non-byline.; Witte Torsten author non-byline.; Kniesch Katja author non-byline.; Azevedo Nancy author non-byline.; Neves Esmeralda author non-byline.; Rao Sambasiva author non-byline.; Jouve Pierre-Emmanuel author non-byline.;
• Is Part Of: Annals of the rheumatic diseases. Volume 79:Issue 9(2020)
• Page Start: 1218
• Page End: 1226
• Publication Date: 2020-06-19
• Subjects: systemic sclerosis -- autoimmune diseases -- epidemiology; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2020-217116
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Objectives: The analysis of annotated transcripts from genome-wide expression studies may help to understand the pathogenesis of complex diseases, such as systemic sclerosis (SSc). We performed a whole blood (WB) transcriptome analysis on RNA collected in the context of the European PRECISESADS project, aiming at characterising the pathways that differentiate SSc from controls and that are reproducible in geographically diverse populations. Methods: Samples from 162 patients and 252 controls were collected in RNA stabilisers. Cases and controls were divided into a discovery (n=79+163; Southern Europe) and validation cohort (n=83+89; Central-Western Europe). RNA sequencing was performed by an Illumina assay. Functional annotations of Reactome pathways were performed with the Functional Analysis of Individual Microarray Expression (FAIME) algorithm. In parallel, immunophenotyping of 28 circulating cell populations was performed. We tested the presence of differentially expressed genes/pathways and the correlation between absolute cell counts and RNA transcripts/FAIME scores in regression models. Results significant in both populations were considered as replicated. Results: Overall, 15 224 genes and 1277 functional pathways were available; of these, 99 and 225 were significant in both sets. Among replicated pathways, we found a deregulation in type-I interferon, Toll-like receptor cascade, tumour suppressor p53 protein function, platelet degranulation and activation. RNA transcripts or FAIME scores were jointly correlated with cell subtypes with strong geographical differences; neutrophils were the major determinant of gene expression in SSc-WB samples. Conclusions: We discovered a set of differentially expressed genes/pathways validated in two independent sets of patients with SSc, highlighting a number of deregulated processes that have relevance for the pathogenesis of autoimmunity and SSc.