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

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...

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Authors: 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; PRECISESADS Clinical Consortium; PRECISESADS Flow Cytometry Consortium; 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
Format: Article
Status:Published version
Publication date:2021
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/179151
Online Access:https://hdl.handle.net/2445/179151
Access Level:Open access
Keyword:Malalties autoimmunitàries
Assaigs clínics
Marcadors bioquímics
Epigenètica
Autoimmune diseases
Clinical trials
Biochemical markers
Epigenetics
Summary: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.

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