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Title: Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients
Author: Beretta, Lorenzo
Barturen, Guillermo
Vigone, Barbara
Bellocchi, Chiara
Hunzelmann, Nicolas
Langhe, Ellen De
Cervera i Segura, Ricard, 1960-
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
PRECISESADS SSc substudy group
PRECISESADS Flow Cytometry study group.
Keywords: Esclerodèrmia
Expressió gènica
Scleroderma (Disease)
Gene expression
Issue Date: Sep-2020
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.
Note: Reproducció del document publicat a:
It is part of: Annals of Rheumatic Disease, 2020, vol. 79, num. 9
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ISSN: 1468-2060
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Medicina)

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