O31 Integrative analysis reveals a molecular stratification of systemic autoimmune diseases. (23rd March 2020)

• Record Type: Journal Article
• Authors: Barturen, Guillermo; Babaei, Sepideh; Català-Moll, Francesc; Martínez-Bueno, Manuel; Makowska, Zuzanna; Martorell-Marugán, Jordi; Carmona-Sáez, Pedro; Toro-Domínguez, Daniel; Carnero-Montoro, Elena; Kerick, Martin; Acosta-Herrera, Marialbert; Lann, Lucas Le; Jamin, Christophe; Rodríguez-Ubreva, Javier; García-Gómez, Antonio; Kageyama, Jorge; Buttgereit, Anne; Hayat, Sikander; Mueller, Joerg; Lesche, Ralf; Hernandez-Fuentes, Maria; Juarez, Maria; Rowley, Tania; White, Ian; Marañón, Concepción; Anjos, Tania Gomes; Varela, Nieves; Aguilar-Quesada, Rocío; Garrancho, Francisco Javier; López-Berrio, Antonio; Maresca, Manuel Rodriguez; Navarro-Linares, Héctor; Almeida, Isabel; Azevedo, Nancy; Brandão, Mariana; Campar, Ana; Faria, Raquel; Farinha, Fátima; Marinho, António; Neves, Esmeralda; Tavares, Ana; Vasconcelos, Carlos; Trombetta, Elena; Montanelli, Gaia; Vigone, Barbara; Alvarez-Errico, Damiana; Li, Tianlu; Alonso, Ricardo Blanco; Martínez, Alfonso Corrales; Genre, Fernanda; Mejías, Raquel López; Gonzalez-Gay, Miguel A; Remuzgo, Sara; Garcia, Begoña Ubilla; Cervera, Ricard; Espinosa, Gerard; Rodríguez-Pintó, Ignasi; Langhe, Ellen De; Cremer, Jonathan; Lories, Rik; Belz, Doreen; Hunzelmann, Nicolas; Baerlecken, Niklas; Kniesch, Katja; Witte, Torsten; Lehner, Michaela; Stummvoll, Georg; Zauner, Michael; Aguirre-Zamorano, Maria Angeles; Barbarroja, Nuria; Castro-Villegas, Maria Carmen; Collantes-Estevez, Eduardo; Ramon, Enrique de; Quintero, Isabel Díaz; Escudero-Contreras, Alejandro; Roldán, María Concepción Fernández; Gómez, Yolanda Jiménez; Moleón, Inmaculada Jiménez; Lopez-Pedrera, Rosario; Ortega-Castro, Rafaela; Ortego, Norberto; Raya, Enrique; Artusi, Carolina; Gerosa, Maria; Meroni, Pier Luigi; Schioppo, Tommaso; Groof, Aurélie De; Ducreux, Julie; Lauwerys, Bernard; Maudoux, Anne-Lise; Cornec, Divi; Devauchelle-Pensec, Valérie; Jousse-Joulin, Sandrine; Jouve, Pierre-Emmanuel; Rouvière, Bénédicte; Saraux, Alain; Simon, Quentin; Alvarez, Montserrat; Chizzolini, Carlo; Dufour, Aleksandra; Wynar, Donatienne; Balog, Attila; Bocskai, Márta; Deák, Magdolna; Dulic, Sonja; Kádár, Gabriella; Kovács, László; Cheng, Qingyu; Gerl, Velia; Hiepe, Falk; Khodadadi, Laleh; Thiel, Silvia; Rinaldis, Emanuele de; Rao, Sambasiva; Benschop, Robert J; Chamberlain, Chris; Dow, Ernst R; Ioannou, Yiannis; Laigle, Laurence; Marovac, Jacqueline; Wojcik, Jerome; Renaudineau, Yves; Borghi, Maria Orietta; Frostegård, Johan; Martín, Javier; Beretta, Lorenzo; Ballestar, Esteban; McDonald, Fiona; Pers, Jacques-Olivier; Alarcón-Riquelme, Marta E;
• Is Part Of: Lupus science & medicine. Volume 7(2020)Supplement 1
• Page Start: A25
• Page End: A25
• Publication Date: 2020-03-23
• Subjects: Systemic lupus erythematosus -- Periodicals; 616.772005
• DOI: 10.1136/lupus-2020-eurolupus.42
• Languages: English
• ISSNs: 2398-8851

Abstract

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.