RT Journal Article
T1 Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases.
A1 Barturen, Guillermo
A1 Babaei, Sepideh
A1 Catala-Moll, Francesc
A1 Martinez-Bueno, Manuel
A1 Makowska, Zuzanna
A1 Martorell-Marugan, Jordi
A1 Carmona-Saez, Pedro
A1 Toro-Dominguez, Daniel
A1 Carnero-Montoro, Elena
A1 Teruel, Maria
A1 Kerick, Martin
A1 Acosta-Herrera, Marialbert
A1 Le Lann, Lucas
A1 Jamin, Christophe
A1 Rodriguez-Ubreva, Javier
A1 Garcia-Gomez, Antonio
A1 Kageyama, Jorge
A1 Buttgereit, Anne
A1 Hayat, Sikander
A1 Mueller, Joerg
A1 Lesche, Ralf
A1 Hernandez-Fuentes, Maria
A1 Juarez, Maria
A1 Rowley, Tania
A1 White, Ian
A1 Marañon, Concepcion
A1 Gomes-Anjos, Tania
A1 Varela, Nieves
A1 Aguilar-Quesada, Rocio
A1 Garrancho, Francisco Javier
A1 Lopez-Berrio, Antonio
A1 Rodriguez-Maresca, Manuel
A1 Navarro-Linares, Hector
A1 Almeida, Isabel
A1 Azevedo, Nancy
A1 Brandão, Mariana
A1 Campar, Ana
A1 Faria, Raquel
A1 Farinha, Fatima
A1 Marinho, António
A1 Neves, Esmeralda
A1 Tavares, Ana
A1 Vasconcelos, Carlos
A1 Trombetta, Elena
A1 Montanelli, Gaia
A1 Vigone, Barbara
A1 Alvarez-Errico, Damiana
A1 Li, Tianlu
A1 Thiagaran, Divya
A1 Blanco-Alonso, Ricardo
A1 Corrales-Martinez, Alfonso
A1 Genre, Fernanda
A1 Lopez-Mejias, Raquel
A1 Gonzalez-Gay, Miguel A
A1 Remuzgo, Sara
A1 Ubilla-Garcia, Begoña
A1 Cervera, Ricard
A1 Espinosa, Gerard
A1 Rodriguez-Pinto, Ignasi
A1 De-Langhe, Ellen
A1 Cremer, Jonathan
A1 Lories, Rik
A1 Belz, Doreen
A1 Hunzelmann, Nicolas
A1 Baerlecken, Niklas
A1 Kniesch, Katja
A1 Witte, Torsten
A1 Lehner, Michaela
A1 Stummvoll, Georg
A1 Zauner, Michael
A1 Aguirre-Zamorano, Maria Angeles
A1 Barbarroja, Nuria
A1 Castro-Villegas, Maria Carmen
A1 Collantes-Estevez, Eduardo
A1 de-Ramon, Enrique
A1 Diaz-Quintero, Isabel
A1 Escudero-Contreras, Alejandro
A1 Fernandez Roldan, Maria Concepcion
A1 Jimenez-Gomez, Yolanda
A1 Jimenez Moleon, Inmaculada
A1 Lopez-Pedrera, Rosario
A1 Ortega-Castro, Rafaela
A1 Ortego, Norberto
A1 Raya, Enrique
A1 Artusi, Carolina
A1 Gerosa, Maria
A1 Meroni, Pier Luigi
A1 Schioppo, Tommaso
A1 De-Groof, Aurelie
A1 Ducreux, Julie
A1 Lauwerys, Bernard
A1 Maudoux, Anne-Lise
A1 Cornec, Divi
A1 Devauchelle-Pensec, Valerie
A1 Jousse-Joulin, Sandrine
A1 Jouve, Pierre-Emmanuel
A1 Rouviere, Benedicte
A1 Saraux, Alain
A1 Simon, Quentin
A1 Alvarez, Montserrat
A1 Chizzolini, Carlo
A1 Dufour, Aleksandra
A1 Wynar, Donatienne
A1 Balog, Attila
A1 Bocskai, Marta
A1 Deak, Magdolna
A1 Dulic, Sonja
A1 Kadar, Gabriella
A1 Kovacs, Laszlo
A1 Cheng, Qingyu
A1 Gerl, Velia
A1 Hiepe, Falk
A1 Khodadadi, Laleh
A1 Thiel, Silvia
A1 de-Rinaldis, Emanuele
A1 Rao, Sambasiva
A1 Benschop, Robert J
A1 Chamberlain, Chris
A1 Dow, Ernst R
A1 Ioannou, Yiannis
A1 Laigle, Laurence
A1 Marovac, Jacqueline
A1 Wojcik, Jerome
A1 Renaudineau, Yves
A1 Borghi, Maria Orietta
A1 Frostegard, Johan
A1 Martin, Javier
A1 Beretta, Lorenzo
A1 Ballestar, Esteban
A1 McDonald, Fiona
A1 Pers, Jacques-Olivier
A1 Alarcon-Riquelme, Marta E
K1 Mixed Connective Tissue Disease
K1 Scleroderma, Systemic
K1 Sjogren's Syndrome
K1 Undifferentiated Connective Tissue Diseases
AB Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups defined by molecular pattern. This study was undertaken to identify molecular clusters for reclassifying systemic autoimmune diseases independently of clinical diagnosis. Unsupervised clustering of integrated whole blood transcriptome and methylome cross-sectional data on 955 patients with 7 systemic autoimmune diseases and 267 healthy controls was undertaken. In addition, an inception cohort was prospectively followed up for 6 or 14 months to validate the results and analyze whether or not cluster assignment changed over time. Four clusters were identified and validated. Three were pathologic, representing "inflammatory," "lymphoid," and "interferon" patterns. Each included all diagnoses and was defined by genetic, clinical, serologic, and cellular features. A fourth cluster with no specific molecular pattern was associated with low disease activity and included healthy controls. A longitudinal and independent inception cohort showed a relapse-remission pattern, where patients remained in their pathologic cluster, moving only to the healthy one, thus showing that the molecular clusters remained stable over time and that single pathogenic molecular signatures characterized each individual patient. Patients with systemic autoimmune diseases can be jointly stratified into 3 stable disease clusters with specific molecular patterns differentiating different molecular disease mechanisms. These results have important implications for future clinical trials and the study of nonresponse to therapy, marking a paradigm shift in our view of systemic autoimmune diseases.
PB Wiley
YR 2021
FD 2021-05-29
LK http://hdl.handle.net/10668/17043
UL http://hdl.handle.net/10668/17043
LA en
NO Barturen G, Babaei S, Català-Moll F, Martínez-Bueno M, Makowska Z, Martorell-Marugán J, et al. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases. Arthritis Rheumatol. 2021 Jun;73(6):1073-1085
DS RISalud
RD Apr 18, 2025