التفاصيل البيبلوغرافية
| العنوان: |
Genome-wide whole blood transcriptome profiling in a large European cohort of systemic sclerosis patients. |
| المؤلفون: |
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, PRECISESADS SSc substudy group |
| المصدر: |
Annals of the Rheumatic Diseases; Sep2020, Vol. 79 Issue 9, p1218-1226, 9p |
| مصطلحات موضوعية: |
RESEARCH, SEQUENCE analysis, RESEARCH methodology, SYSTEMIC scleroderma, CELL receptors, MICROARRAY technology, EVALUATION research, MEDICAL cooperation, CELLULAR signal transduction, INTERFERONS, COMPARATIVE studies, IMMUNITY, GENE expression profiling, IMMUNOPHENOTYPING, LONGITUDINAL method, BLOOD |
| مصطلحات جغرافية: |
EUROPE |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
|
Copyright of Annals of the Rheumatic Diseases is the property of BMJ Publishing Group and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
