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

Perrine Soret 1 Christelle Le Dantec 2 Emiko Desvaux 1, 2 Nathan Foulquier 2 Bastien Chassagnol 1 Sandra Hubert 1 Christophe Jamin 2 Guillermo Barturen 3 Guillaume Desachy 1 Valérie Devauchelle-Pensec 2, 4 Cheïma Boudjeniba 1 Divi Cornec 2, 4 Alain Saraux 2, 4 Sandrine Jousse-Joulin 2, 4 Nuria Barbarroja 5 Ignasi Rodríguez-Pintó 6 Ellen de Langhe 7 Lorenzo Beretta 8 Carlo Chizzolini 9 László Kovács 10 Torsten Witte 11 Eléonore Bettacchioli 12 Anne Buttgereit 13 Zuzanna Makowska 13 Ralf Lesche 13 Maria Orietta Borghi 14 Javier Martin 15 Sophie Courtade-Gaiani 1 Laura Xuereb 1 Mickaël Guedj 1 Philippe Moingeon 1 Marta Alarcón-Riquelme 16 Laurence Laigle 1 Jacques-Olivier Pers 2, 12 Barbara Vigone 17 Bernard Lauwerys Anne-Lise Maudoux Carlos Vasconcelos Ana Tavares Raquel Faria Mariana Brandão Ana Campar António Marinho Fátima Farinha Isabel Almeida Miguel Angel Gonzalez-Gay Mantecón Ricardo Blanco Alonso Alfonso Corrales Martínez Ricard Cervera Gerard Espinosa Rik Lories Nicolas Hunzelmann Doreen Belz Niklas Baerlecken Georg Stummvoll Michael Zauner Michaela Lehner Eduardo Collantes Rafaela Ortega-Castro Ma Angeles Aguirre-Zamorano Alejandro Escudero-Contreras Ma Carmen Castro-Villegas Yolanda Jiménez Gómez Norberto Ortego María Concepción Fernández Roldán Enrique Raya Inmaculada Jiménez Moleón Enrique de Ramon Isabel Díaz Quintero Pier Luigi Meroni Maria Gerosa Tommaso Schioppo Carolina Artusi Aleksandra Zuber Donatienne Wynar Attila Balog Magdolna Deák Márta Bocskai Sonja Dulic Gabriella Kádár Falk Hiepe Silvia Thiel Manuel Rodriguez Maresca Antonio López-Berrio Rocío Aguilar-Quesada Héctor Navarro-Linares Yiannis Ioannou Chris Chamberlain Jacqueline Marovac Marta Alarcón Riquelme Tania Gomes Anjos Concepción Marañón Lucas Le Lann Quentin Simon Bénédicte Rouvière Nieves Varela Brian Muchmore Aleksandra Dufour Montserrat Alvarez Jonathan Cremer Chary Lopez-Pedrera Velia Gerl Laleh Khodadadi Qingyu Cheng Aurélie de Groof Julie Ducreux Elena Trombetta Tianlu Li Damiana Alvarez-Errico Katja Kniesch Nancy Azevedo Esmeralda Neves Sambasiva Rao Pierre-Emmanuel Jouve
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.
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https://hal.univ-brest.fr/hal-03301637
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Submitted on : Tuesday, July 27, 2021 - 3:47:45 PM
Last modification on : Tuesday, October 19, 2021 - 10:56:58 PM

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Perrine Soret, Christelle Le Dantec, Emiko Desvaux, Nathan Foulquier, Bastien Chassagnol, et al.. A new molecular classification to drive precision treatment strategies in primary Sjögren’s syndrome. Nature Communications, Nature Publishing Group, 2021, 12 (1), pp.3523. ⟨10.1038/s41467-021-23472-7⟩. ⟨hal-03301637⟩

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