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

Autor: Zuzanna Makowska, Ricard Cervera, Lorenzo Beretta, László Kovács, Marta E. Alarcón-Riquelme, Guillermo Barturen, Isabel Almeida, Divi Cornec, Javier Martín, Jacques-Olivier Pers, Ellen De Langhe, Nicolas Hunzelmann, Carlo Chizzolini, Maria Gerosa, Martin Kerick, Ralf Lesche, Chiara Bellocchi, Barbara Vigone, Rafaela Ortega Castro
Přispěvatelé: Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centre for Genomics and Oncological Research Pfizer [Granada, Spain], Universidad de Granada = University of Granada (UGR)-Andalusian Regional Government [Granada, Spain], Università degli Studi di Milano = University of Milan (UNIMI), Universitätsklinikum Köln (Uniklinik Köln), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], Department of Clinical Sciences and Community Health [Milan, Italy], Hospital Clinic, IDIBAPS, Universidad de Barcelona, Ciberes, Barcelona, Spain., Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), Universidad de Córdoba = University of Córdoba [Córdoba]-Hospital Universitario Reina Sofía, University of Szeged [Szeged], CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Hôpital Universitaire de Genève, Geneva, Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Bayer Pharma AG [Berlin], Instituto de Parasitología y Biomedicina 'López-Neyra', PRECISESADS SSc substudy group, PRECISESADS Flow Cytometry study group : Doreen Belz, Eduardo Collantes-Estevez, Francesca Ingegnoli, Yolanda Jimenez Gómez, Chary Lopez Pedrera, Rik Lories, Gaia Montanelli, Silvia Piantoni, Ignasi Rodriguez Pinto, Carlos Vasconcelos, Christophe Jamin, Concepción Marañón, Lucas Le Lann, Quentin Simon, Bénédicte Rouvière, Nieves Varela, Brian Muchmore, Aleksandra Dufour, Montserrat Alvarez, Jonathan Cremer, Nuria Barbarroja, Velia Gerl, Laleh Khodadadi, Qingyu Cheng, Anne Buttgereit, Aurélie De Groof, Julie Ducreux, Elena Trombetta, Tianlu Li, Damiana Alvarez-Errico, Torsten Witte, Katja Kniesch, Nancy Azevedo, Esmeralda Neves, Sambasiva Rao, Pierre-Emmanuel Jouve., Michel, Geneviève, University of Granada [Granada]-Andalusian Regional Government [Granada, Spain], University of Milan, University Hospitals Leuven and Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium, Università degli Studi di Milano [Milano] (UNIMI), Universidad de Córdoba [Cordoba]-Hospital Universitario Reina Sofía, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Universitaire de Genève, European Commission
Rok vydání: 2020
Předmět:
MESH: Interferon Type I
MESH: Signal Transduction
Male
0301 basic medicine
Microarray
systemic sclerosis
Autoimmunity
Diseases
Pathogenesis
DISEASE
MESH: Scleroderma
Systemic
Cohort Studies
Transcriptome
0302 clinical medicine
Immunophenotyping
Platelet degranulation
Gene expression
MESH: Sequence Analysis
RNA
Immunology and Allergy
Medicine
RNA-Seq
MESH: Cohort Studies
GENE-EXPRESSION
MESH: Aged
MESH: Middle Aged
Toll-Like Receptors
Middle Aged
3. Good health
Europe
Interferon Type I
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
epidemiology
Life Sciences & Biomedicine
MESH: Toll-Like Receptors
Signal Transduction
Adult
MESH: Immunophenotyping
[SDV.IMM] Life Sciences [q-bio]/Immunology
Immunology
Context (language use)
Systemic Sclerosis
Computational biology
General Biochemistry
Genetics and Molecular Biology
MESH: Gene Expression Profiling
03 medical and health sciences
Rheumatology
MESH: Autoimmunity
Humans
autoimmune diseases
Gene
Aged
030203 arthritis & rheumatology
Science & Technology
MESH: Humans
Scleroderma
Systemic
Sequence Analysis
RNA
business.industry
MESH: Transcriptome
Gene Expression Profiling
RNA
MESH: Adult
Microarray Analysis
Expressió gènica
MESH: Male
MESH: Microarray Analysis
Scleroderma (Disease)
030104 developmental biology
MESH: Genome-Wide Association Study
MESH: Europe
Esclerodèrmia
business
MESH: Female
Genome-Wide Association Study
Zdroj: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Agência para a Sociedade do Conhecimento (UMIC)-FCT-Sociedade da Informação
instacron:RCAAP
Annals of the Rheumatic Diseases
Annals of the Rheumatic Diseases, 2020, 79 (9), pp.1218-1226. ⟨10.1136/annrheumdis-2020-217116⟩
Annals of the Rheumatic Diseases, BMJ Publishing Group, 2020, 79 (9), pp.1218-1226. ⟨10.1136/annrheumdis-2020-217116⟩
Dipòsit Digital de la UB
Universidad de Barcelona
Digibug. Repositorio Institucional de la Universidad de Granada
instname
Digibug: Repositorio Institucional de la Universidad de Granada
Universidad de Granada (UGR)
Digital.CSIC. Repositorio Institucional del CSIC
ISSN: 1468-2060
0003-4967
DOI: 10.1136/annrheumdis-2020-217116
Popis: 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.
This work was supported by eU/eFPia/innovative Medicines initiative Joint Undertaking PrecisesaDs Grant no. 115 565.
Databáze: OpenAIRE
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