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Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients

2020Journal article Open access
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dc.contributor.authorBeretta, Lorenzo
dc.contributor.authorBarturen, Guillermo
dc.contributor.authorVigone, Barbara
dc.contributor.authorBellocchi, Chiara
dc.contributor.authorHunzelmann, Nicolas
dc.contributor.authorDe Langhe, Ellen
dc.contributor.authorCervera, Ricard
dc.contributor.authorGerosa, Maria
dc.contributor.authorKovács, László
dc.contributor.authorOrtega Castro, Rafaela
dc.contributor.authorAlmeida, Isabel
dc.contributor.authorCornec, Divi
dc.contributor.authorChizzolini, Carlo
dc.contributor.authorPers, Jacques-Olivier
dc.contributor.authorMakowska, Zuzanna
dc.contributor.authorLesche, Ralf
dc.contributor.authorKerick, Martin
dc.contributor.authorAlarcón-Riquelme, Marta Eugenia
dc.contributor.authorMartin, Javier
dc.date.accessioned2021-07-02T19:16:51Z
dc.date.available2021-07-02T19:16:51Z
dc.date.issued2020
dc.description.abstractObjectives: 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.pt_PT
dc.description.sponsorshipThis work was supported by eU/eFPia/innovative Medicines initiative Joint Undertaking PRECISESADs Grant no. 115 565pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBeretta L, Barturen G, Vigone B, Bellocchi C, Hunzelmann N, De Langhe E, Cervera R, Gerosa M, Kovács L, Ortega Castro R, Almeida I, Cornec D, Chizzolini C, Pers JO, Makowska Z, Lesche R, Kerick M, Alarcón-Riquelme ME, Martin J; PRECISESADS SSc substudy group; PRECISESADS Flow Cytometry study group. Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients. Ann Rheum Dis. 2020 Sep;79(9):1218-1226. doi: 10.1136/annrheumdis-2020-217116. Epub 2020 Jun 19. PMID: 32561607; PMCID: PMC7456554.pt_PT
dc.identifier.doi10.1136/annrheumdis-2020-217116pt_PT
dc.identifier.issn1468-2060
dc.identifier.urihttp://hdl.handle.net/10400.16/2484
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherBMJpt_PT
dc.relation.publisherversionhttps://ard.bmj.com/content/79/9/1218.longpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectautoimmune diseasespt_PT
dc.subjectepidemiologypt_PT
dc.subjectsystemic sclerosispt_PT
dc.titleGenome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patientspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceEnglandpt_PT
oaire.citation.endPage1226pt_PT
oaire.citation.issue9pt_PT
oaire.citation.startPage1218pt_PT
oaire.citation.titleAnnals of the rheumatic diseasespt_PT
oaire.citation.volume79pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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