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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases
Arthritis and Rheumatology, Volume 73, No. 6, Year 2021
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Description
Objective: Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis. Methods: Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time. Results: Four clusters were identified and validated. Three were pathologic, representing “inflammatory,” “lymphoid,” and “interferon” patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse–remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient. Conclusion: Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases. © 2020, American College of Rheumatology
Authors & Co-Authors
Kerick, Martin
Spain, Madrid
Consejo Superior de Investigaciones Científicas
Jamin, Christophe
France, Brest
Centre Hospitalier Universitaire de Brest
Hayat, Sikander
Germany, Leverkusen
Bayer ag
Almeida, Isabel M.
Unknown Affiliation
Faria, Raquel M.
Unknown Affiliation
Marinho, António A.P.
Unknown Affiliation
Neves, Esmeralda
Unknown Affiliation
Vasconcelos, Carlos A.C.
Unknown Affiliation
Blanco-Alonso, Ricardo
Spain, Santander
Universidad de Cantabria
Corrales, Alfonso F.
Spain, Santander
Universidad de Cantabria
Genre, Fernanda
Spain, Santander
Universidad de Cantabria
López-Mejías, Raquel
Spain, Santander
Universidad de Cantabria
González-Gay, Miguel Ángel
Spain, Santander
Universidad de Cantabria
Cervera, Ricard
Spain, Barcelona
Hospital Clinic Barcelona
Espinosa, Gerard
Spain, Barcelona
Hospital Clinic Barcelona
Rodríguez-Pintó, Ignasi
Spain, Barcelona
Hospital Clinic Barcelona
de Langhe, Ellen
Belgium, Leuven
Ku Leuven– University Hospital Leuven
Hunzelmann, Nicolas
Germany, Koln
Uniklinik Köln
Baerlecken, Niklas Thomas
Germany, Hannover
Hannover Medical School
Witte, Torsten
Germany, Hannover
Hannover Medical School
Aguirre, Mª Angeles
Spain, Cordoba
Universidad de Córdoba
Barbarroja, Nuria
Spain, Cordoba
Universidad de Córdoba
Collantes, Eduardo
Spain, Cordoba
Universidad de Córdoba
de Rámon, Enrique
Spain, Malaga
Hospital Regional Universitario Carlos Haya
Escudero-Contreras, A.
Spain, Cordoba
Universidad de Córdoba
Ortega-Castro, Rafaela
Spain, Cordoba
Universidad de Córdoba
Raya Álvarez, Enriqué G.
Spain, Granada
Complejo Hospitalario Universitario de Granada
Gerosa, Maria
Italy, Milan
Università Degli Studi Di Milano
Meroni, Pier Luigi
Italy, Milan
Università Degli Studi Di Milano
Lauwerys, Bernard R.
Belgium, Brussels
Cliniques Universitaires Saint-luc
Cornec, Divi Y.K.
France, Brest
Centre Hospitalier Universitaire de Brest
Devauchelle-Pensec, Valérie
France, Brest
Centre Hospitalier Universitaire de Brest
Jousse-Joulin, Sandrine
France, Brest
Centre Hospitalier Universitaire de Brest
Saraux, Alain
France, Brest
Centre Hospitalier Universitaire de Brest
Chizzolini, Carlo
Switzerland, Geneva
Hôpitaux Universitaires de Genève
Hiepe, Falk
Germany, Berlin
Charité – Universitätsmedizin Berlin
de Rinaldis, Emanuele
United States, Cambridge
Sanofi
Renaudineau, Yves
France, Brest
Centre Hospitalier Universitaire de Brest
Borghi, Maria Orietta
Italy, Milan
Irccs Istituto Auxologico Italiano
Frostegård, Johan
Sweden, Stockholm
Karolinska Institutet
Martin, Javier
Spain, Madrid
Consejo Superior de Investigaciones Científicas
Beretta, Lorenzo
Italy, Milan
Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico
Pers, Jacques-Olivier Olivier
France, Brest
Centre Hospitalier Universitaire de Brest
Alarcón-Riquelme, Marta Eugenia
Unknown Affiliation
Statistics
Citations: 66
Authors: 44
Affiliations: 27
Identifiers
Doi:
10.1002/art.41610
ISSN:
23265191
Research Areas
Genetics And Genomics
Health System And Policy
Study Design
Cross Sectional Study
Cohort Study