Медицинская библиотека · Arthritis & rheumatology (Hoboken, N.J.) · 2021

Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases.

Barturen Guillermo, Babaei Sepideh, Català-Moll Francesc, Martínez-Bueno Manuel, Makowska Zuzanna, Martorell-Marugán Jordi, Carmona-Sáez Pedro, Toro-Domínguez Daniel, Carnero-Montoro Elena, Teruel María, Kerick Martin, Acosta-Herrera Marialbert, Le Lann Lucas, 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, Gomes Anjos Tania, Varela Nieves, Aguilar-Quesada Rocío, Garrancho Francisco Javier, López-Berrio Antonio, Rodriguez Maresca Manuel, 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, Thiagaran Divya, Blanco Alonso Ricardo, Corrales Martínez Alfonso, Genre Fernanda, López Mejías Raquel, Gonzalez-Gay Miguel A, Remuzgo Sara, Ubilla Garcia Begoña, Cervera Ricard, Espinosa Gerard, Rodríguez-Pintó Ignasi, De Langhe Ellen, 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, de Ramon Enrique, Díaz Quintero Isabel, Escudero-Contreras Alejandro, Fernández Roldán María Concepción, Jiménez Gómez Yolanda, Jiménez Moleón Inmaculada, Lopez-Pedrera Rosario, Ortega-Castro Rafaela, Ortego Norberto, Raya Enrique, Artusi Carolina, Gerosa Maria, Meroni Pier Luigi, Schioppo Tommaso, De Groof Aurélie, 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, de Rinaldis Emanuele, 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

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Аннотация

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Для цитирования: Barturen Guillermo, Babaei Sepideh, Català-Moll Francesc, Martínez-Bueno Manuel, Makowska Zuzanna, Martorell-Marugán Jordi, Carmona-Sáez Pedro, Toro-Domínguez Daniel, Carnero-Montoro Elena, Teruel María, Kerick Martin, Acosta-Herrera Marialbert, Le Lann Lucas, 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, Gomes Anjos Tania, Varela Nieves, Aguilar-Quesada Rocío, Garrancho Francisco Javier, López-Berrio Antonio, Rodriguez Maresca Manuel, 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, Thiagaran Divya, Blanco Alonso Ricardo, Corrales Martínez Alfonso, Genre Fernanda, López Mejías Raquel, Gonzalez-Gay Miguel A, Remuzgo Sara, Ubilla Garcia Begoña, Cervera Ricard, Espinosa Gerard, Rodríguez-Pintó Ignasi, De Langhe Ellen, 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, de Ramon Enrique, Díaz Quintero Isabel, Escudero-Contreras Alejandro, Fernández Roldán María Concepción, Jiménez Gómez Yolanda, Jiménez Moleón Inmaculada, Lopez-Pedrera Rosario, Ortega-Castro Rafaela, Ortego Norberto, Raya Enrique, Artusi Carolina, Gerosa Maria, Meroni Pier Luigi, Schioppo Tommaso, De Groof Aurélie, 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, de Rinaldis Emanuele, 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. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases.. Arthritis & rheumatology (Hoboken, N.J.). 2021. DOI: 10.1002/art.41610.

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