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1. Interferon and B-cell Signatures Inform Precision Medicine in Lupus Nephritis

Author

Beretta, Lorenzo, Vigone, Barbara, Pers, Jacques-Olivier, Saraux, Alain, Devauchelle-Pensec, Valérie, Cornec, Divi, Jousse-Joulin, Sandrine, Lauwerys, Bernard, Ducreux, Julie, Maudoux, Anne-Lise, Vasconcelos, Carlos, Tavares, Ana, Neves, Esmeralda, Faria, Raquel, Brandão, Mariana, Campar, Ana, Marinho, António, Farinha, Fátima, Almeida, Isabel, Gonzalez-Gay Mantecón, Miguel Angel, Alonso, Ricardo Blanco, Martínez, Alfonso Corrales, Cervera, Ricard, Rodríguez-Pintó, Ignasi, Espinosa, Gerard, Lories, Rik, De Langhe, Ellen, Hunzelmann, Nicolas, Belz, Doreen, Witte, Torsten, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega-Castro, Rafaela, Aguirre-Zamorano, Ma Angeles, Escudero-Contreras, Alejandro, Castro-Villegas, Ma Carmen, Ortego, Norberto, Fernández Roldán, María Concepción, Raya, Enrique, Moleón, Inmaculada Jiménez, de Ramon, Enrique, Quintero, Isabel Díaz, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, Chizzolini, Carlo, Zuber, Aleksandra, Wynar, Donatienne, Kovács, Laszló, Balog, Attila, Deák, Magdolna, Bocskai, Márta, Dulic, Sonja, Kádár, Gabriella, Hiepe, Falk, Gerl, Velia, Thiel, Silvia, Maresca, Manuel Rodriguez, López-Berrio, Antonio, Aguilar-Quesada, Rocío, Navarro-Linares, Héctor, Parodis, Ioannis, Lindblom, Julius, Toro-Domínguez, Daniel, Borghi, Maria O., Castillo, Jessica, Carnero-Montoro, Elena, Enman, Yvonne, Mohan, Chandra, Alarcón-Riquelme, Marta E., Barturen, Guillermo, and Nikolopoulos, Dionysis

Published
2024
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2. Interferon and B-cell Signatures Inform Precision Medicine in Lupus Nephritis

Author

Parodis, Ioannis, primary, Lindblom, Julius, additional, Toro-Domínguez, Daniel, additional, Beretta, Lorenzo, additional, Borghi, Maria O., additional, Castillo, Jessica, additional, Carnero-Montoro, Elena, additional, Enman, Yvonne, additional, Mohan, Chandra, additional, Alarcón-Riquelme, Marta E., additional, Barturen, Guillermo, additional, Nikolopoulos, Dionysis, additional, Vigone, Barbara, additional, Pers, Jacques-Olivier, additional, Saraux, Alain, additional, Devauchelle-Pensec, Valérie, additional, Cornec, Divi, additional, Jousse-Joulin, Sandrine, additional, Lauwerys, Bernard, additional, Ducreux, Julie, additional, Maudoux, Anne-Lise, additional, Vasconcelos, Carlos, additional, Tavares, Ana, additional, Neves, Esmeralda, additional, Faria, Raquel, additional, Brandão, Mariana, additional, Campar, Ana, additional, Marinho, António, additional, Farinha, Fátima, additional, Almeida, Isabel, additional, Gonzalez-Gay Mantecón, Miguel Angel, additional, Alonso, Ricardo Blanco, additional, Martínez, Alfonso Corrales, additional, Cervera, Ricard, additional, Rodríguez-Pintó, Ignasi, additional, Espinosa, Gerard, additional, Lories, Rik, additional, De Langhe, Ellen, additional, Hunzelmann, Nicolas, additional, Belz, Doreen, additional, Witte, Torsten, additional, Baerlecken, Niklas, additional, Stummvoll, Georg, additional, Zauner, Michael, additional, Lehner, Michaela, additional, Collantes, Eduardo, additional, Ortega-Castro, Rafaela, additional, Aguirre-Zamorano, Ma Angeles, additional, Escudero-Contreras, Alejandro, additional, Castro-Villegas, Ma Carmen, additional, Ortego, Norberto, additional, Fernández Roldán, María Concepción, additional, Raya, Enrique, additional, Moleón, Inmaculada Jiménez, additional, de Ramon, Enrique, additional, Quintero, Isabel Díaz, additional, Meroni, Pier Luigi, additional, Gerosa, Maria, additional, Schioppo, Tommaso, additional, Artusi, Carolina, additional, Chizzolini, Carlo, additional, Zuber, Aleksandra, additional, Wynar, Donatienne, additional, Kovács, Laszló, additional, Balog, Attila, additional, Deák, Magdolna, additional, Bocskai, Márta, additional, Dulic, Sonja, additional, Kádár, Gabriella, additional, Hiepe, Falk, additional, Gerl, Velia, additional, Thiel, Silvia, additional, Maresca, Manuel Rodriguez, additional, López-Berrio, Antonio, additional, Aguilar-Quesada, Rocío, additional, and Navarro-Linares, Héctor, additional

Published
2024
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3. A new molecular classification to drive precision treatment strategies in primary Sjögren’s syndrome

Author

Soret, Perrine, Le Dantec, Christelle, Desvaux, Emiko, Foulquier, Nathan, Chassagnol, Bastien, Hubert, Sandra, Christophe, Jamin, Barturen, Guillermo, Desachy, Guillaume, Devauchelle-Pensec, Valérie, Boudjeniba, Cheïma, Cornec, Divi, Saraux, Alain, Jousse-Joulin, Sandrine, Barbarroja, Nuria, Rodríguez-Pintó, Ignasi, de Langhe, Ellen, Beretta, Lorenzo, Chizzolini, Carlo, Kovács, László, Witte, Torsten, Bettacchioli, Eléonore, Buttgereit, Anne, Makowska, Zuzanna, Lesche, Ralf, Borghi, Maria Orietta, Martin, Javier, Courtade-Gaiani, Sophie, Xuereb, Laura, Guedj, Mickaël, Moingeon, Philippe, Alarcón-Riquelme, Marta, Laigle, Laurence, Pers, Jacques-Olivier, Vigone, Barbara, Lauwerys, Bernard, Maudoux, Anne-Lise, Vasconcelos, Carlos, Tavares, Ana, Faria, Raquel, Brandão, Mariana, Campar, Ana, Marinho, António, Farinha, Fátima, Almeida, Isabel, Gonzalez-Gay Mantecón, Miguel Angel, Blanco Alonso, Ricardo, Corrales Martínez, Alfonso, Cervera, Ricard, Espinosa, Gerard, Lories, Rik, Hunzelmann, Nicolas, Belz, Doreen, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega-Castro, Rafaela, Aguirre-Zamorano, Ma Angeles, Escudero-Contreras, Alejandro, Castro-Villegas, Ma Carmen, Jiménez Gómez, Yolanda, Ortego, Norberto, Fernández Roldán, María Concepción, Raya, Enrique, Jiménez Moleón, Inmaculada, de Ramon, Enrique, Díaz Quintero, Isabel, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, Zuber, Aleksandra, Wynar, Donatienne, Balog, Attila, Deák, Magdolna, Bocskai, Márta, Dulic, Sonja, Kádár, Gabriella, Hiepe, Falk, Thiel, Silvia, Rodriguez Maresca, Manuel, López-Berrio, Antonio, Aguilar-Quesada, Rocío, Navarro-Linares, Héctor, Ioannou, Yiannis, Chamberlain, Chris, Marovac, Jacqueline, Alarcón Riquelme, Marta, Gomes Anjos, Tania, Marañón, Concepción, Le Lann, Lucas, Simon, Quentin, Rouvière, Bénédicte, Varela, Nieves, Muchmore, Brian, Dufour, Aleksandra, Alvarez, Montserrat, Cremer, Jonathan, Lopez-Pedrera, Chary, Gerl, Velia, Khodadadi, Laleh, Cheng, Qingyu, de Groof, Aurélie, Ducreux, Julie, Trombetta, Elena, Li, Tianlu, Alvarez-Errico, Damiana, Kniesch, Katja, Azevedo, Nancy, Neves, Esmeralda, Rao, Sambasiva, Jouve, Pierre-Emmanuel, Institut de Recherches Internationales Servier [Suresnes] (IRIS), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre for Genomics and Oncological Reearch (GENYO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), Universidad de Córdoba = University of Córdoba [Córdoba]-Hospital Universitario Reina Sofía, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Maggiore Hospital, IRCCS Foundation, Milano, Department of Pathology and Immunology [Geneva, Switzerland], Université de Genève = University of Geneva (UNIGE), University of Szeged [Szeged], Clinic for Immunology and Rhematology, Hannover Medical School, Hanover, Germany, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Pharmaceuticals Division Bayer Pharma Aktiengesellschaft, Università degli Studi di Milano = University of Milan (UNIMI), Instituto de Parasitología y Biomedicina 'López-Neyra' (IPBLN), Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Granada = University of Granada (UGR), and Michel, Geneviève

Subjects
MESH: Databases, Protein, MESH: Inflammation, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Flow Cytometry, MESH: Cross-Sectional Studies, MESH: DNA Methylation, MESH: Computer Simulation, cell cycle, chronic lymphocytic leukemia, liquid chromatography-tandem mass spectrometry, splicing, MESH: Autoantibodies, MESH: Interferons, MESH: RNA-Seq, MESH: Cohort Studies, MESH: Databases, Genetic, MESH: Cytokines, MESH: Humans, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, MESH: Transcriptome, MESH: Adult, MESH: Chemokines, MESH: Male, MESH: Proteome, MESH: Sjogren's Syndrome, MESH: Genome-Wide Association Study, MESH: Biomarkers, MESH: Multigene Family, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Female, MESH: Computational Biology
Abstract

International audience; 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.

Published
2021

4. Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

Author

Teruel, María, Barturen, Guillermo, Martínez Bueno, Manuel, Castellini Pérez, Olivia, Barroso Gil, Miguel, Povedano, Elena, Kerick, Martin, Català Moll, Francesc, Makowska, Zuzanna, Buttgereit, Anne, Beretta, Lorenzo, Chizzolini, Carlo, Zuber, Aleksandra, Wynar, Donatienne, Kovács, Laszló, Balog, Attila, Deák, Magdolna, Bocskai, Márta, Dulic, Sonja, Kádár, Gabriella, Hiepe, Falk, Gerl, Velia, Thiel, Silvia, Rodriguez Maresca, Manuel, López Berrio, Antonio, Aguilar Quesada, Rocío, Navarro Linares, Héctor, Alvarez, Montserrat, Álvarez Errico, Damiana, Azevedo, Nancy, Barbarroja, Nuria, Cheng, Qingyu, Cremer, Jonathan, Groof, Aurélie de, Langhe, Ellen de, Ducreux, Julie, Dufour, Aleksandra, Hernández Fuentes, María, Khodadadi, Laleh, Kniesch, Katja, Li, Tianlu, López Pedrera, Chary, Marañón, Concepción, Muchmore, Brian, Neves, Esmeralda, Rouvière, Bénédicte, Simon, Quentin, Trombetta, Elena, Varela, Nieves, Witte, Torsten, Pers, Jacques-olivier, Ballestar, Esteban, Martin, Javier, Carnero Montoro, Elena, Alarcón Riquelme, Marta, Precisesads Clinical Consortium, Precisesads Flow Cytometry Study Group, Vigone, Barbara, Pers, Jacques Olivier, Saraux, Alain, Devauchelle-Pensec, Valérie, Cornec, Divi, Jousse-Joulin, Sandrine, Lauwerys, Bernard, Maudoux, Anne-lise, Vasconcelos, Carlos, Tavares, Ana, Faria, Raquel, Brandão, Mariana, Campar, Ana, Marinho, António, Farinha, Fátima, Almeida, Isabel, Gonzalez-Gay Mantecón, Miguel Ángel, Blanco Alonso, Ricardo, Corrales Martínez, Alfonso, Cervera, Ricard, Rodríguez Pintó, Ignasi, Espinosa, Gerard, Lories, Rik, Hunzelmann, Nicolas, Belz, Doreen, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega Castro, Rafaela, Aguirre Zamorano, Mª Angeles, Escudero Contreras, Alejandro, Castro Villegas, Mª Carmen, Ortego, Norberto, Fernández Roldán, María Concepción, Raya, Enrique, Jiménez Moleón, Inmaculada, Ramon, Enrique de, Díaz Quintero, Isabel, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, PRECISESADS Clinical Consortium, PRECISESADS Flow Cytometry Study Group, [Teruel,M, Barturen,G, Martínez-Bueno,M, Castellini-Pérez,O, Barroso-Gil,M, Povedano,E, Marañón,C, Carnero-Montoro,E, Alarcón-Riquelme,ME] GENYO, Center for Genomics and Oncological Research Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain. [Kerick,M, Martin,J] IPBLN-CSIC, Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científcas, Granada, Spain. [Català-Moll,F, Ballestar,E] Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC), Badalona, Barcelona, Spain. [Català-Moll,F, Ballestar,E] IDIBELL, Bellvitge Biomedical Research Institute L’Hospitalet de Llobregat, Barcelona, Spain. [Makowska,Z, Buttgereit,A] Pharmaceuticals Division, Bayer Pharma Aktiengesellschaft, Berlin, Germany. [Pers,JO] Université de Brest, INSERM, Labex IGO, CHU de Brest, Brest, France.[Alarcón-Riquelme,ME] Institute for Environmental Medicine, Karolinska Institutet, Solna, Sweden., and Funding for the preparation of this manuscript has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement nº 115,565, resources composed of the financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013) and the EFPIA companies’ in kind contribution. MT is supported by a Spanish grant from Health Department, Junta de Andalucía (PI/0017/2016) and through the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806975. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. EC-M was funded by the Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness (FJCI_2014_20652). We thank Ralf Lesche for the production of RNASeq data and Marc Torres Ciuró for design support.

Subjects
Epigenomics, Male, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation [Medical Subject Headings], Autoimmune diseases, Gene Expression, Quantitative trait, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Interferons [Medical Subject Headings], 0302 clinical medicine, Rheumatic diseases, HLA Antigens, Genetics, Regulation of gene expression, 0303 health sciences, education.field_of_study, Multidisciplinary, Malalties autoimmunitàries, Molecular medicine, Epigenetic, Autoanticuerpos, Genomics, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Genomics::Epigenomics [Medical Subject Headings], 3. Good health, Sjogren's Syndrome, DNA methylation, Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::DNA Methylation [Medical Subject Headings], Medicine, Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::HLA Antigens [Medical Subject Headings], Epigenetics, Female, Phenomena and Processes::Genetic Phenomena::Genetic Variation [Medical Subject Headings], Extracellular matrix organization, Science, Population, Check Tags::Male [Medical Subject Headings], Human leukocyte antigen, Biology, Variación genética, Article, 03 medical and health sciences, Rheumatology, Enfermedades autoinmunes, Diseases::Immune System Diseases::Autoimmune Diseases [Medical Subject Headings], Immunogenetics, Diseases::Immune System Diseases::Autoimmune Diseases::Arthritis, Rheumatoid::Sjogren's Syndrome [Medical Subject Headings], Humans, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies [Medical Subject Headings], education, Gene, 030304 developmental biology, Autoantibodies, 030203 arthritis & rheumatology, Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic [Medical Subject Headings], Genetic Variation, DNA Methylation, Epigenètica, Check Tags::Female [Medical Subject Headings], Gene Expression Regulation, Epigenómica, Síndrome de Sjögren, Interferons, Expresión génica
Abstract

Funding for the preparation of this manuscript has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no 115,565, resources composed of the financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013) and the EFPIA companies' in kind contribution. MT is supported by a Spanish grant from Health Department, Junta de Andalucia (PI/0017/2016) and through the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806975. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. EC-M was funded by the Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness (FJCI_2014_20652). We thank Ralf Lesche for the production of RNASeq data and Marc Torres Ciuro for design support., Primary Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population., Innovative Medicines Initiative Joint Undertaking from the European Union's Seventh Framework Program (FP7/2007-2013) 115,565, EFPIA companies, Junta de Andalucia PI/0017/2016, Innovative Medicines Initiative 2 Joint Undertaking 806975 European Union's Horizon 2020 research and innovation programme, EFPIA, Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness FJCI_2014_20652

Published
2021

5. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases.

Author

UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Alarcón-Riquelme, Marta E, Benschop, Robert J, 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, Chamberlain, Chris, Dufour, Aleksandra, 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, Wynar, Donatienne, 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, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de rhumatologie, Alarcón-Riquelme, Marta E, Benschop, Robert J, 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, Chamberlain, Chris, Dufour, Aleksandra, 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, Wynar, Donatienne, 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, and Chizzolini, Carlo

Abstract

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.

Published
2021

6. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases

Author

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

Published
2021
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7. O31 Integrative analysis reveals a molecular stratification of systemic autoimmune diseases

Author

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

Published
2020
Full Text
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8. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases

Author

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

Published
2020
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