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
(14)
,
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
1
IRIS -
Institut de Recherches Internationales Servier [Suresnes]
2 LBAI - Lymphocytes B, Autoimmunité et Immunothérapies
3 Centre for Genomics and Oncological Reearch (GENYO)
4 CHU - BREST - Rhumato - CHRU Brest - Service de Rhumatologie
5 IMIBIC - Instituto Maimonides de Investigación Biomédica de Cordoba
6 Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
7 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
8 Maggiore Hospital, IRCCS Foundation, Milano
9 Department of Pathology and Immunology [Geneva, Switzerland]
10 University of Szeged [Szeged]
11 Clinic for Immunology and Rhematology, Hannover Medical School, Hanover, Germany
12 CHU - BREST - Hôpital Morvan - CHRU de Brest
13 Pharmaceuticals Division Bayer Pharma Aktiengesellschaft
14 UNIMI - Università degli Studi di Milano = University of Milan
15 IPBLN - Instituto de Parasitología y Biomedicina “López-Neyra”
16 UGR - Universidad de Granada = University of Granada
2 LBAI - Lymphocytes B, Autoimmunité et Immunothérapies
3 Centre for Genomics and Oncological Reearch (GENYO)
4 CHU - BREST - Rhumato - CHRU Brest - Service de Rhumatologie
5 IMIBIC - Instituto Maimonides de Investigación Biomédica de Cordoba
6 Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
7 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
8 Maggiore Hospital, IRCCS Foundation, Milano
9 Department of Pathology and Immunology [Geneva, Switzerland]
10 University of Szeged [Szeged]
11 Clinic for Immunology and Rhematology, Hannover Medical School, Hanover, Germany
12 CHU - BREST - Hôpital Morvan - CHRU de Brest
13 Pharmaceuticals Division Bayer Pharma Aktiengesellschaft
14 UNIMI - Università degli Studi di Milano = University of Milan
15 IPBLN - Instituto de Parasitología y Biomedicina “López-Neyra”
16 UGR - Universidad de Granada = University of Granada
Christophe Jamin
- Function : Author
- PersonId : 2136
- IdHAL : christophe-jamin
- ORCID : 0000-0002-9494-3223
- IdRef : 116289511
Valérie Devauchelle-Pensec
- Function : Author
- PersonId : 766858
- ORCID : 0000-0003-0432-825X
Divi Cornec
- Function : Author
- PersonId : 766860
- ORCID : 0000-0002-9159-702X
Alain Saraux
- Function : Author
- PersonId : 762362
- ORCID : 0000-0002-8454-7067
Sandrine Jousse-Joulin
- Function : Author
- PersonId : 766854
- ORCID : 0000-0002-5479-5887
Carlo Chizzolini
- Function : Author
- PersonId : 767598
- ORCID : 0000-0003-4849-6335
Jacques-Olivier Pers
- Function : Author
- PersonId : 753610
- IdHAL : jacques-olivier-pers
- ORCID : 0000-0001-7287-5541
- IdRef : 068262159
Bernard Lauwerys
- Function : Author
Anne-Lise Maudoux
- Function : Author
Carlos Vasconcelos
- Function : Author
Ana Tavares
- Function : Author
Raquel Faria
- Function : Author
Mariana Brandão
- Function : Author
Ana Campar
- Function : Author
António Marinho
- Function : Author
Fátima Farinha
- Function : Author
Isabel Almeida
- Function : Author
Miguel Angel Gonzalez-Gay Mantecón
- Function : Author
Ricardo Blanco Alonso
- Function : Author
Alfonso Corrales Martínez
- Function : Author
Ricard Cervera
- Function : Author
Gerard Espinosa
- Function : Author
Rik Lories
- Function : Author
Nicolas Hunzelmann
- Function : Author
Doreen Belz
- Function : Author
Niklas Baerlecken
- Function : Author
Georg Stummvoll
- Function : Author
Michael Zauner
- Function : Author
Michaela Lehner
- Function : Author
Eduardo Collantes
- Function : Author
Rafaela Ortega-Castro
- Function : Author
Ma Angeles Aguirre-Zamorano
- Function : Author
Alejandro Escudero-Contreras
- Function : Author
Ma Carmen Castro-Villegas
- Function : Author
Yolanda Jiménez Gómez
- Function : Author
Norberto Ortego
- Function : Author
María Concepción Fernández Roldán
- Function : Author
Enrique Raya
- Function : Author
Inmaculada Jiménez Moleón
- Function : Author
Enrique de Ramon
- Function : Author
Isabel Díaz Quintero
- Function : Author
Pier Luigi Meroni
- Function : Author
Maria Gerosa
- Function : Author
Tommaso Schioppo
- Function : Author
Carolina Artusi
- Function : Author
Aleksandra Zuber
- Function : Author
Donatienne Wynar
- Function : Author
Attila Balog
- Function : Author
Magdolna Deák
- Function : Author
Márta Bocskai
- Function : Author
Sonja Dulic
- Function : Author
Gabriella Kádár
- Function : Author
Falk Hiepe
- Function : Author
Silvia Thiel
- Function : Author
Manuel Rodriguez Maresca
- Function : Author
Antonio López-Berrio
- Function : Author
Rocío Aguilar-Quesada
- Function : Author
Héctor Navarro-Linares
- Function : Author
Yiannis Ioannou
- Function : Author
Chris Chamberlain
- Function : Author
Jacqueline Marovac
- Function : Author
Marta Alarcón Riquelme
- Function : Author
Tania Gomes Anjos
- Function : Author
Concepción Marañón
- Function : Author
Lucas Le Lann
- Function : Author
Quentin Simon
- Function : Author
Bénédicte Rouvière
- Function : Author
Nieves Varela
- Function : Author
Brian Muchmore
- Function : Author
Aleksandra Dufour
- Function : Author
Montserrat Alvarez
- Function : Author
Jonathan Cremer
- Function : Author
Chary Lopez-Pedrera
- Function : Author
Velia Gerl
- Function : Author
Laleh Khodadadi
- Function : Author
Qingyu Cheng
- Function : Author
Aurélie de Groof
- Function : Author
Julie Ducreux
- Function : Author
Elena Trombetta
- Function : Author
Tianlu Li
- Function : Author
Damiana Alvarez-Errico
- Function : Author
Katja Kniesch
- Function : Author
Nancy Azevedo
- Function : Author
Esmeralda Neves
- Function : Author
Sambasiva Rao
- Function : Author
Pierre-Emmanuel Jouve
- Function : Author
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.