RT Journal Article
T1 Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients.
A1 Beretta, Lorenzo
A1 Barturen, Guillermo
A1 Vigone, Barbara
A1 Bellocchi, Chiara
A1 Hunzelmann, Nicolas
A1 De Langhe, Ellen
A1 Cervera, Ricard
A1 Gerosa, Maria
A1 Kovacs, Lászlo
A1 Ortega Castro, Rafaela
A1 Almeida, Isabel
A1 Cornec, Divi
A1 Chizzolini, Carlo
A1 Pers, Jacques-Olivier
A1 Makowska, Zuzanna
A1 Lesche, Ralf
A1 Kerick, Martin
A1 Alarcon-Riquelme, Marta Eugenia
A1 Martin, Javier
K1 Autoimmune diseases
K1 Epidemiology
K1 Systemic sclerosis
AB 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. 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. 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. 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.
PB BMJ Group
YR 2020
FD 2020-05-14
LK http://hdl.handle.net/10668/15780
UL http://hdl.handle.net/10668/15780
LA en
NO Beretta L, Barturen G, Vigone B, Bellocchi C, Hunzelmann N, De Langhe E, et al. Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients. Ann Rheum Dis. 2020 Sep;79(9):1218-1226
DS RISalud
RD Apr 7, 2025