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, Lorenzo Beretta, Barbara Vigone, Jacques‐Olivier Pers, Alain Saraux, Valérie Devauchelle‐Pensec, Divi Cornec, Sandrine Jousse-Joulin, Bernard Lauwerys, Julie Ducreux, Anne‐Lise Maudoux, Carlos Vasconcelos, Ana Tavares, Esmeralda Neves, Raquel Faria, Mariana Brandão, Ana Campar, António Marinho, Fátima Farinha, Isabel Almeida, Miguel Á. González‐Gay, Ricardo Blanco, Alfonso Corrales Martínez, Ricard Cervera, Ignasi Rodríguez‐Pintó, Gerard Espinosa, Rik Lories, Ellen De Langhe, Nicolas Hunzelmann, Doreen Belz, Torsten Witte, Niklas Baerlecken, Georg Stummvoll, Michael Zauner, Michaela Lehner, Eduardo Collantes‐Estévez, R. Ortega Castro, M. Á. Aguirre, Alejandro Escudero-Contreras, Ma Carmen Castro‐Villegas, Yolanda Jiménez, Norberto Ortego, María Concepción Fernández Roldán, Enrique Raya, Inmaculada Jiménez Moleón, Enrique de Ramón, Isabel Díaz Quintero, Pier Luigi Meroni, Maria Gerosa, Tommaso Schioppo, Carolina Artusi, Carlo Chizzolini, Aleksandra Zuber, Donatienne Wynar, László Kovács, Attila Balog, Magdolna Deák, Márta Bocskai, Sonja Dulic, Gabriella Kádár, Falk Hiepe, Velia Gerl, Silvia Thiel, Manuel Rodríguez Maresca, Antonio López‐Berrio, Rocío Aguilar‐Quesada, Héctor Navarro‐Linares, Yiannis Ioannou, Chris Chamberlain, Jacqueline Marovac, Marta Alarcón Riquelme, Tania Gomes Anjos, Christophe Jamin, Concepción Marañón, Lucas Le Lann, Quentin Simon, Bénédicte Rouvière, Nieves Varela, Brian Muchmore, Aleksandra Maria Dufour
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.