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

PRECISESADS Clinical Consortium, PRECISESADS Flow Cytometry Consortium, 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 BerettaCarlo Chizzolini, László Kovács, Torsten Witte, Eléonore Bettacchioli, Anne Buttgereit, Zuzanna Makowska, Ralf Lesche, Maria Orietta Borghi, J Martin, Sophie Courtade-Gaiani , Laura Xuereb, Mickaël Guedj, P. Moingeon, Marta E. Alarcón-Riquelme, Laurence Laigle, Jacques Olivier Pers

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number3523
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2021

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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