1. A new molecular classification to drive precision treatment strategies in primary Sjögren's syndrome
- Author
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Soret, Perrine, Le Dantec, Christelle, Desvaux, Emiko, Foulquier, Nathan, Chassagnol, Bastien, Hubert, Sandra, Jamin, Christophe, Barturen, Guillermo, Desachy, Guillaume, Devauchelle-Pensec, Valérie, Boudjeniba, Cheïma, Cornec, Divi, Saraux, Alain, Jousse-Joulin, Sandrine, Barbarroja, Nuria, Rodríguez-Pintó, Ignasi, De Langhe, Ellen, Beretta, Lorenzo, Chizzolini, Carlo, Kovács, László, Witte, Torsten, Bettacchioli, Eléonore, Buttgereit, Anne, Makowska, Zuzanna, Lesche, Ralf, Borghi, Maria Orietta, Martin, Javier, Courtade-Gaiani, Sophie, Xuereb, Laura, Guedj, Mickaël, Moingeon, Philippe, Alarcón-Riquelme, Marta, Laigle, Laurence, Pers, Jacques-Olivier, Vigone, Barbara, Lauwerys, Bernard, Maudoux, Anne-Lise, Vasconcelos, Carlos, Tavares, Ana, Faria, Raquel, Brandão, Mariana, Campar, Ana, Marinho, António, Farinha, Fátima, Almeida, Isabel, Gonzalez-Gay Mantecón, Miguel Angel, Blanco Alonso, Ricardo, Corrales Martínez, Alfonso, Cervera, Ricard, Espinosa, Gerard, Lories, Rik, Hunzelmann, Nicolas, Belz, Doreen, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega-Castro, Rafaela, Aguirre-Zamorano, Ma Angeles, Escudero-Contreras, Alejandro, Castro-Villegas, Ma Carmen, Jiménez Gómez, Yolanda, Ortego, Norberto, Fernández Roldán, María Concepción, Raya, Enrique, Jiménez Moleón, Inmaculada, de Ramon, Enrique, Díaz Quintero, Isabel, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, Zuber, Aleksandra, Wynar, Donatienne, Balog, Attila, Deák, Magdolna, Bocskai, Márta, Dulic, Sonja, Kádár, Gabriella, Hiepe, Falk, Thiel, Silvia, Rodriguez Maresca, Manuel, López-Berrio, Antonio, Aguilar-Quesada, Rocío, Navarro-Linares, Héctor, Ioannou, Yiannis, Chamberlain, Chris, Marovac, Jacqueline, Alarcón Riquelme, Marta, Gomes Anjos, Tania, Marañón, Concepción, Le Lann, Lucas, Simon, Quentin, Rouvière, Bénédicte, Varela, Nieves, Muchmore, Brian, Dufour, Aleksandra, Alvarez, Montserrat, Cremer, Jonathan, Lopez-Pedrera, Chary, Gerl, Velia, Khodadadi, Laleh, Cheng, Qingyu, De Groof, Aurélie, Ducreux, Julie, Trombetta, Elena, Li, Tianlu, Alvarez-Errico, Damiana, Kniesch, Katja, Azevedo, Nancy, Neves, Esmeralda, Rao, Sambasiva, Jouve, Pierre-Emmanuel, Agence Nationale de la Recherche (France), European Commission, 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), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Cluj-Napoca Unit-The Net-Work of International Francophone Clinical Epidemiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca Unit-The Net-Work of International Francophone Clinical Epidemiology, Iuliu Hatieganu University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania., Iuliu Hatieganu University of Medicine & Pharmacy, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), University of South Florida [Tampa] (USF), Cluj-Napoca Unit-The Net-Work of International Francophone Clinical Epidemiology, Iuliu Hatieganu University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania., Institut de Recherches Internationales Servier [Suresnes] (IRIS), Centre for Genomics and Oncological Reearch (GENYO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), Universidad de Córdoba [Cordoba]-Hospital Universitario Reina Sofía, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University Hospitals Leuven and Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium, Maggiore Hospital, IRCCS Foundation, Milano, Department of Pathology and Immunology [Geneva, Switzerland], University of Geneva [Switzerland], University of Szeged [Szeged], Clinic for Immunology and Rhematology, Hannover Medical School, Hanover, Germany, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Pharmaceuticals Division Bayer Pharma Aktiengesellschaft, Università degli Studi di Milano [Milano] (UNIMI), Instituto de Parasitología y Biomedicina 'López-Neyra' (IPBLN), Consejo Superior de Investigaciones Científicas (CSIC), Centre for Genomics and Oncological Research (GENYO) Pfizer, University of Granada, and Università degli Studi di Milano and IRCCS Maggiore Policlinico Hospital, Mangiagalli and Regina Elena Foundation
- Subjects
Male ,Oncology ,MESH: Inflammation ,MESH: Flow Cytometry ,Disease ,DISEASE ,0302 clinical medicine ,Molecular classification ,Databases, Genetic ,MESH: Interferons ,Databases, Protein ,MESH: Cytokines ,MESH: Middle Aged ,Molecular medicine ,Malalties autoimmunitàries ,MESH: Polymorphism, Single Nucleotide ,ASSOCIATION ,Flow Cytometry ,Pathophysiology ,3. Good health ,Multigene Family ,Marcadors bioquímics ,Cohort ,Cytokines ,Science & Technology - Other Topics ,Epigenetics ,cell cycle ,MESH: Computational Biology ,medicine.medical_specialty ,Science ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,splicing ,MESH: Cross-Sectional Studies ,Rheumatology ,MESH: Computer Simulation ,Humans ,Computer Simulation ,RITUXIMAB ,SIGNATURES ,Autoantibodies ,Science & Technology ,MESH: Humans ,MESH: Transcriptome ,Computational Biology ,MESH: Adult ,DNA Methylation ,Immune dysregulation ,Epigenètica ,Clinical trial ,CLINICAL PHENOTYPES ,Cross-Sectional Studies ,030104 developmental biology ,MESH: Sjogren's Syndrome ,MESH: Genome-Wide Association Study ,chronic lymphocytic leukemia ,MESH: Multigene Family ,MESH: Female ,Biomarkers ,RESPONSES ,0301 basic medicine ,Proteome ,Autoimmune diseases ,General Physics and Astronomy ,medicine.disease_cause ,Cohort Studies ,Clinical trials ,MESH: DNA Methylation ,MESH: Autoantibodies ,RNA-Seq ,liquid chromatography-tandem mass spectrometry ,MESH: Cohort Studies ,MESH: Databases, Genetic ,Multidisciplinary ,Biochemical markers ,Middle Aged ,MESH: Chemokines ,Multidisciplinary Sciences ,MESH: Proteome ,Sjogren's Syndrome ,Assaigs clinics ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,Chemokines ,HYDROXYCHLOROQUINE ,Adult ,INTERFERON ,MESH: Databases, Protein ,MEDLINE ,Polymorphism, Single Nucleotide ,MECHANISMS ,Internal medicine ,cell cycle, chronic lymphocytic leukemia, liquid chromatography-tandem mass spectrometry, splicing ,medicine ,MESH: RNA-Seq ,Inflammation ,030203 arthritis & rheumatology ,business.industry ,General Chemistry ,EFFICACY ,MESH: Male ,MESH: Biomarkers ,Interferons ,Transcriptome ,business ,Assaigs clínics ,Genome-Wide Association Study - Abstract
There is currently no approved treatment for primary Sjögren’s syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics. Here, we report, in a cross-sectional cohort, a molecular classification scheme for Sjögren’s syndrome patients based on the multi-omic profiling of whole blood samples from a European cohort of over 300 patients, and a similar number of age and gender-matched healthy volunteers. Using transcriptomic, genomic, epigenetic, cytokine expression and flow cytometry data, combined with clinical parameters, we identify four groups of patients with distinct patterns of immune dysregulation. The biomarkers we identify can be used by machine learning classifiers to sort future patients into subgroups, allowing the re-evaluation of response to treatments in clinical trials., Sjögren’s syndrome, a disease that primarily affects women, is poorly understood. Here, the authors combine data from a large cohort of patients and healthy controls to identify biomarkers that distinguish patient subgroups to improve our understanding of the disease and facilitate drug development.
- Published
- 2021