A new molecular classification to drive precision treatment strategies in primary Sjögren’s syndrome
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, Beretta Lorenzo , Vigone Barbara , Pers Jacques-Olivier , Saraux Alain , Devauchelle-Pensec Valérie , Cornec Divi , Jousse-Joulin Sandrine , Lauwerys Bernard , Ducreux Julie , Maudoux Anne-Lise , Vasconcelos Carlos , Tavares Ana , Neves Esmeralda , 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 , Rodríguez-Pintó Ignasi , Espinosa Gerard , Lories Rik , De Langhe Ellen , Hunzelmann Nicolas , Belz Doreen , Witte Torsten , 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 , Chizzolini Carlo , Zuber Aleksandra , Wynar Donatienne , Kovács Laszló , Balog Attila , Deák Magdolna , Bocskai Márta , Dulic Sonja , Kádár Gabriella , Hiepe Falk , Gerl Velia , 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 ,   PRECISESADS Flow Cytometry Consortium, Jamin Christophe , Marañón Concepción , Le Lann Lucas , Simon Quentin , Rouvière Bénédicte , Varela Nieves , Muchmore Brian , Dufour Aleksandra , Alvarez Montserrat , Chizzolini Carlo , Cremer Jonathan , De Langhe Ellen , Barbarroja Nuria , Lopez-Pedrera Chary , Gerl Velia , Khodadadi Laleh , Cheng Qingyu , Buttgereit Anne , Makowska Zuzanna , De Groof Aurélie , Ducreux Julie , Trombetta Elena , Li Tianlu , Alvarez-Errico Damiana , Witte Torsten , Kniesch Katja , Azevedo Nancy , Neves Esmeralda , Rao Sambasiva , Jouve Pierre-Emmanuel , Pers Jacques-Olivier , 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 E. , Laigle Laurence , Pers Jacques-Olivier 
Published: June 2021

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.