Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients.
Adult
Aged
Autoimmunity
/ genetics
Cohort Studies
Europe
Female
Gene Expression Profiling
Genome-Wide Association Study
Humans
Immunophenotyping
Interferon Type I
/ blood
Male
Microarray Analysis
Middle Aged
Scleroderma, Systemic
/ genetics
Sequence Analysis, RNA
Signal Transduction
/ genetics
Toll-Like Receptors
/ blood
Transcriptome
/ genetics
autoimmune diseases
epidemiology
systemic sclerosis
Journal
Annals of the rheumatic diseases
ISSN: 1468-2060
Titre abrégé: Ann Rheum Dis
Pays: England
ID NLM: 0372355
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
10
02
2020
revised:
30
04
2020
accepted:
14
05
2020
pubmed:
21
6
2020
medline:
2
10
2020
entrez:
21
6
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32561607
pii: annrheumdis-2020-217116
doi: 10.1136/annrheumdis-2020-217116
pmc: PMC7456554
doi:
Substances chimiques
Interferon Type I
0
Toll-Like Receptors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1218-1226Investigateurs
Doreen Belz
(D)
Eduardo Collantes-Estevez
(E)
Francesca Ingegnoli
(F)
Yolanda Jimenez Gómez
(YJ)
Chary Lopez Pedrera
(CL)
Rik Lories
(R)
Gaia Montanelli
(G)
Silvia Piantoni
(S)
Ignasi Rodriguez Pinto
(IR)
Carlos Vasconcelos
(C)
Christophe Jamin
(C)
Concepción Marañón
(C)
Lucas Le Lann
(LL)
Quentin Simon
(Q)
Bénédicte Rouvière
(B)
Nieves Varela
(N)
Brian Muchmore
(B)
Aleksandra Dufour
(A)
Montserrat Alvarez
(M)
Jonathan Cremer
(J)
Nuria Barbarroja
(N)
Velia Gerl
(V)
Laleh Khodadadi
(L)
Qingyu Cheng
(Q)
Anne Buttgereit
(A)
Aurélie De Groof
(A)
Julie Ducreux
(J)
Elena Trombetta
(E)
Tianlu Li
(T)
Damiana Alvarez-Errico
(D)
Torsten Witte
(T)
Katja Kniesch
(K)
Nancy Azevedo
(N)
Esmeralda Neves
(E)
Sambasiva Rao
(S)
Pierre-Emmanuel Jouve
(PE)
Informations de copyright
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
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