A new molecular classification to drive precision treatment strategies in primary Sjögren’s syndrome

Perrine Soret, Christelle Le Dantec, Emiko Desvaux, Nathan Foulquier, Bastien Chassagnol, Sandra Hubert, Christophe Jamin, Guillermo Barturen, Guillaume Desachy, Valérie Devauchelle-Pensec, Cheïma Boudjeniba, Divi Cornec, Alain Saraux, Sandrine Jousse-Joulin, Nuria Barbarroja, Ignasi Rodríguez-Pintó, Ellen De Langhe, Lorenzo Beretta, Carlo Chizzolini, László Kovács, Torsten Witte, Eléonore Bettacchioli, Anne Buttgereit, Zuzanna Makowska, Ralf Lesche, Maria Orietta Borghi, Javier Martin, Sophie Courtade-Gaiani, Laura Xuereb, Mickaël Guedj, Philippe Moingeon, Marta E. Alarcón-Riquelme, Laurence Laigle and Jacques-Olivier Pers ()
Additional contact information
Perrine Soret: Institut de Recherches Internationales Servier, Departments of Translational Medicine and Immuno-Inflammatory Diseases Research and Development
Christelle Le Dantec: Univ Brest, Inserm
Emiko Desvaux: Institut de Recherches Internationales Servier, Departments of Translational Medicine and Immuno-Inflammatory Diseases Research and Development
Nathan Foulquier: Univ Brest, Inserm
Bastien Chassagnol: Institut de Recherches Internationales Servier, Departments of Translational Medicine and Immuno-Inflammatory Diseases Research and Development
Sandra Hubert: Institut de Recherches Internationales Servier, Departments of Translational Medicine and Immuno-Inflammatory Diseases Research and Development
Christophe Jamin: Univ Brest, Inserm
Guillermo Barturen: Center for Genomics and Oncological Research (GENYO)
Guillaume Desachy: Institut de Recherches Internationales Servier, Departments of Translational Medicine and Immuno-Inflammatory Diseases Research and Development
Valérie Devauchelle-Pensec: Univ Brest, Inserm
Cheïma Boudjeniba: Institut de Recherches Internationales Servier, Departments of Translational Medicine and Immuno-Inflammatory Diseases Research and Development
Divi Cornec: Univ Brest, Inserm
Alain Saraux: Univ Brest, Inserm
Sandrine Jousse-Joulin: Univ Brest, Inserm
Nuria Barbarroja: University of Cordoba
Ignasi Rodríguez-Pintó: Institut d’Investigacions Biomèdiques August Pi i Sunyer
Ellen De Langhe: KU Leuven and Division of Rheumatology
Lorenzo Beretta: Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico di Milano
Carlo Chizzolini: University Hospital and School of Medicine
László Kovács: University of Szeged
Torsten Witte: Medical University Hannover
Eléonore Bettacchioli: CHU de Brest
Anne Buttgereit: Bayer Pharma Aktiengesellschaft
Zuzanna Makowska: Bayer Pharma Aktiengesellschaft
Ralf Lesche: Bayer Pharma Aktiengesellschaft
Maria Orietta Borghi: Università degli studi di Milano
Javier Martin: Consejo Superior de Investigaciones Científicas (IPBLN-CSIC)
Sophie Courtade-Gaiani: Institut de Recherches Internationales Servier, Departments of Translational Medicine and Immuno-Inflammatory Diseases Research and Development
Laura Xuereb: Institut de Recherches Internationales Servier, Departments of Translational Medicine and Immuno-Inflammatory Diseases Research and Development
Mickaël Guedj: Institut de Recherches Internationales Servier, Departments of Translational Medicine and Immuno-Inflammatory Diseases Research and Development
Philippe Moingeon: Institut de Recherches Internationales Servier, Departments of Translational Medicine and Immuno-Inflammatory Diseases Research and Development
Marta E. Alarcón-Riquelme: Center for Genomics and Oncological Research (GENYO)
Laurence Laigle: Institut de Recherches Internationales Servier, Departments of Translational Medicine and Immuno-Inflammatory Diseases Research and Development
Jacques-Olivier Pers: Univ Brest, Inserm

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-23472-7

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