1. O31 Integrative analysis reveals a molecular stratification of systemic autoimmune diseases
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Carlo Chizzolini, Yolanda Jiménez Gómez, Pier Luigi Meroni, M.C. Castro-Villegas, Ralf Lesche, Fernanda Genre, Javier Martín, Raquel Faria, Márta Bocskai, Tommaso Schioppo, Emanuele de Rinaldis, Divi Cornec, Torsten Witte, Pierre-Emmanuel Jouve, Sikander Hayat, Johan Frostegård, Guillermo Barturen, Christophe Jamin, Laleh Khodadadi, Alfonso Corrales Martínez, Quentin Simon, Mariana Brandão, Chris Chamberlain, Alain Saraux, Javier Rodríguez-Ubreva, Francesc Català-Moll, Michaela Lehner, Ricard Cervera, Tania F. Rowley, Tianlu Li, Attila Balog, Enrique de Ramón, Maria Angeles Aguirre-Zamorano, Elena Carnero-Montoro, Rafaela Ortega-Castro, László Kovács, Velia Gerl, Carolina Artusi, Nancy Azevedo, Martin Kerick, Antonio López-Berrio, Esmeralda Neves, Anne-Lise Maudoux, Bénédicte Rouvière, Bernard Lauwerys, Maria Gerosa, Yiannis Ioannou, Fátima Farinha, Ian White, Tania Anjos, Sepideh Babaei, N.T. Baerlecken, Katja Kniesch, Jonathan Cremer, Joerg Mueller, Julie Ducreux, Lucas Le Lann, Norberto Ortego, Jerome Wojcik, Marialbert Acosta-Herrera, Maria Hernandez-Fuentes, Héctor Navarro-Linares, Maria Orietta Borghi, Inmaculada Jiménez Moleón, António Marinho, Rocío Aguilar-Quesada, Enrique Raya, Falk Hiepe, Raquel López Mejías, Mcdonald Fiona Mcdougall, Robert J. Benschop, Georg Stummvoll, Isabel Díaz Quintero, Esteban Ballestar, Aleksandra Maria Dufour, Jordi Martorell-Marugán, Elena Trombetta, Manuel Rodriguez Maresca, Miguel A. González-Gay, Valérie Devauchelle-Pensec, Maria Juarez, Carlos Vasconcelos, Doreen Belz, Yves Renaudineau, Donatienne Wynar, Jacqueline Marovac, Aurélie De Groof, Sandrine Jousse-Joulin, Alejandro Escudero-Contreras, Laurence Laigle, Ignasi Rodríguez-Pintó, Zuzanna Makowska, Isabel Almeida, Lorenzo Beretta, Damiana Álvarez-Errico, Nieves Varela, Montserrat Alvarez, Concepción Marañón, Ricardo Blanco Alonso, Daniel Toro-Domínguez, Ana Campar, Manuel Martínez-Bueno, Barbara Vigone, Francisco Javier Garrancho, Rik Lories, Gabriella Kádár, Michael Zauner, Silvia Thiel, Pedro Carmona-Sáez, María Concepción Fernández Roldán, Magdolna Deák, Marta E. Alarcón-Riquelme, Rosario Lopez-Pedrera, Qingyu Cheng, Sonja Dulic, Sara Remuzgo, Ana Lisa Taylor Tavares, Gerard Espinosa, Gaia Montanelli, Nuria Barbarroja, Sambasiva P. Rao, Eduardo Collantes-Estevez, Anne Buttgereit, Begoña Ubilla Garcia, Ernst R. Dow, Jorge Kageyama, Antonio Garcia-Gomez, Jacques-Olivier Pers, Nicolas Hunzelmann, and Ellen De Langhe
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Oncology ,medicine.medical_specialty ,Disease clusters ,business.industry ,Disease progression ,INCEPTION COHORT ,Internal medicine ,T cell immunity ,medicine ,Effective treatment ,Christian ministry ,Medical diagnosis ,business ,Unsupervised clustering - Abstract
Background Clinical heterogeneity, a hallmark of systemic autoimmune diseases (SADs) impedes early diagnosis and effective treatment, issues that may be addressed if patients could be grouped into a molecular defined stratification. Methods With the aim of reclassifying SADs independently of the clinical diagnoses, unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data of 918 patients with 7 SADs and 263 healthy controls was undertaken. An inception cohort prospectively followed for 6 and 14 months was studied to validate the results in early cases and analyze if cluster assignment was modified with time. Results Four clusters were identified Three aberrant clusters were ‘acute phase inflammatory’, ‘T cell immunity’, and ‘interferon’, each including all diagnoses, were defined by genetic, clinical, serological and cellular features. A fourth cluster showed no specific molecular pattern, to which 74% of healthy controls clustered with patients. The inception cohort showed that most patients were either assigned always to the same cluster or moved from the healthy-like cluster to a single aberrant cluster resembling the relapsing-remitting dynamic of these diseases, showing that single aberrant molecular signatures characterize each individual patient. Conclusions Patients with SADs share molecular signatures and can be therefore stratified into three disease clusters differentiating each patient into a specific molecular disease pathway. Such assignment is stable with time. These results have important implications for understanding disease progression and therapy design marking a paradigm shift in our view of SADs. Acknowledgment This work has been supported through a grant from the Innovative Medicines Initiative Joint Undertaking No. 115565 and in-kind and in-cash contributions from the EFPIA partners. G.B. is supported by the Instituto de Salud Carlos III (ISCIII, Spanish Health Ministry), through the Sara Borrell subprogram (CD18/00153). The authors would like to particularly express their gratitude to the patients, nurses and many others who helped directly or indirectly in the consecution of this study.
- Published
- 2020
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