ArticleArthritis & rheumatology (Hoboken, N.J.)2021
Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases.
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Article in Arthritis & rheumatology (Hoboken, N.J.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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94citing papers in PubMed
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94 citing papers in PubMed.
- Myocardial injury in systemic lupus erythematosus and lupus nephritis: a silent threat.Clinical kidney journal · 2026Review
- Clinical and Ultrasonographic Characterization of Proposed Sjögren's Disease Phenotypes in a Korean Longitudinal Cohort.Journal of clinical medicine · 2026Article
- Methylation and polygenic risk scores capture different features of Systemic Lupus Erythematosus.Rheumatology (Oxford, England) · 2026Article
- From Molecular Pathophysiology to Clinical Trial Design in Sjögren's Disease: A Three-Axis Framework.International journal of molecular sciences · 2026Review
- Digital twins to accelerate target identification and drug development for immune-mediated disorders.FEBS open bio · 2026Review
- A symposium update on the key perspectives in systemic sclerosis and systemic lupus erythematosus.Journal of translational autoimmunity · 2026Review
- Lupus trials and tribulations: are outcome measures the problem?EULAR rheumatology open · 2026Review
- GEDO: topology-based inference of gene module activity in Sjögren's disease.Briefings in bioinformatics · 2026Article
- A transcriptional patient map of systemic lupus erythematosus reveals disease-related multicellular immune programs conserved between blood and kidney.bioRxiv : the preprint server for biology · 2026Article
- Molecular Stratification of Antiphospholipid Syndrome Through Integrative Analysis of the Whole-Blood RNA Transcriptome.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Unsupervised clustering of clinical and laboratory features of systemic lupus erythematosus: insights from a multicentre cohort.Lupus science & medicine · 2026Article
- The SjD Map: an interactive pathway tour into Sjögren's disease signalling mechanisms.NPJ systems biology and applications · 2026Article
- Single-cell Unperturbed Activation Profiling by mass cytometry capturesFrontiers in immunology · 2026Article
- Assessing the translational relevance of specific molecular pathways in spontaneous lupus mouse models.Frontiers in immunology · 2026Article
- SLE-diseaseome: a comprehensive meta-collection of systemic lupus erythematosus relevant functional pathways.Bioinformatics advances · 2026Article
- A study of gene expression in the living human brain.Molecular psychiatry · 2026Article
- Clinical features, diagnosis, and treatment of primary Sjögren's disease with interstitial lung disease: A narrative review.Frontiers in immunology · 2026Review
- A decision tree-based algorithm for structured risk stratification of rare rheumatic diseases in a tertiary referral setting.Frontiers in medicine · 2026Article
- Transcriptome analysis unveils Th1 cell cycle signature as a distinctive feature of mixed connective tissue disease.Arthritis research & therapy · 2025Article
- Dysregulation of innate and adaptive lymphoid immunity may have implications for symptom attribution and predict responses to targeted therapies in neuropsychiatric systemic lupus erythematosus.Journal of translational autoimmunity · 2025Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
132 authors.
Guillermo BarturenPfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research, Granada, Spain.ORCID 0000-0003-2103-1028
Sepideh BabaeiBayer, Berlin, Germany.
Francesc Català-MollBellvitge Biomedical Research Institute, Barcelona, Spain.
Manuel Martínez-BuenoPfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research, Granada, Spain.
Zuzanna MakowskaBayer, Berlin, Germany.
Jordi Martorell-MarugánPfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research, Granada, Spain.ORCID 0000-0002-5186-0735
Pedro Carmona-SáezPfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research, Granada, Spain.
Daniel Toro-DomínguezPfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research, Granada, Spain.ORCID 0000-0001-8440-312X
Elena Carnero-MontoroPfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research, Granada, Spain.
María TeruelPfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research, Granada, Spain.
Martin KerickInstitute of Parasitology and Biomedicine "López Neyra", Spanish National Research Council, Granada, Spain.
Marialbert Acosta-HerreraInstitute of Parasitology and Biomedicine "López Neyra", Spanish National Research Council, Granada, Spain.
Lucas Le LannUniversité de Brest, Centre Hospitalier Universitaire de Brest, INSERM, and Labex IGO, Brest, France.
Christophe JaminUniversité de Brest, Centre Hospitalier Universitaire de Brest, INSERM, and Labex IGO, Brest, France.
Javier Rodríguez-UbrevaBellvitge Biomedical Research Institute, Barcelona, Spain.
Antonio García-GómezBellvitge Biomedical Research Institute, Barcelona, Spain.
Jorge KageyamaBayer, Berlin, Germany.
Anne ButtgereitBayer, Berlin, Germany.
Sikander HayatBayer, Berlin, Germany.
Joerg MuellerBayer, Berlin, Germany.
Ralf LescheBayer, Berlin, Germany.
Maria Hernandez-FuentesUCB, Slough, UK.
Maria JuarezUCB, Slough, UK.
Tania RowleyUCB, Slough, UK.
Ian WhiteUCB, Slough, UK.
Concepción MarañónPfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research, Granada, Spain.
Tania Gomes AnjosPfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research, Granada, Spain.
Nieves VarelaPfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research, Granada, Spain.
Rocío Aguilar-QuesadaAndalusian Public Health System Biobank, Granada, Spain.
Francisco Javier GarranchoAndalusian Public Health System Biobank, Granada, Spain.
Antonio López-BerrioAndalusian Public Health System Biobank, Granada, Spain.
Manuel Rodriguez MarescaAndalusian Public Health System Biobank, Granada, Spain.
Héctor Navarro-LinaresAndalusian Public Health System Biobank, Granada, Spain.
Isabel AlmeidaCentro Hospitalar do Porto, Porto, Portugal.
Nancy AzevedoCentro Hospitalar do Porto, Porto, Portugal.
Mariana BrandãoCentro Hospitalar do Porto, Porto, Portugal.
Ana CamparCentro Hospitalar do Porto, Porto, Portugal.
Raquel FariaCentro Hospitalar do Porto, Porto, Portugal.
Fátima FarinhaCentro Hospitalar do Porto, Porto, Portugal.
António MarinhoCentro Hospitalar do Porto, Porto, Portugal.
Esmeralda NevesCentro Hospitalar do Porto, Porto, Portugal.
Ana TavaresCentro Hospitalar do Porto, Porto, Portugal.
Carlos VasconcelosCentro Hospitalar do Porto, Porto, Portugal.
Elena TrombettaFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Gaia MontanelliFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Barbara VigoneFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Damiana Alvarez-ErricoBellvitge Biomedical Research Institute, Barcelona, Spain.
Tianlu LiBellvitge Biomedical Research Institute, Barcelona, Spain.
Divya ThiagaranKarolinska Institutet, Stockholm, Sweden.
Ricardo Blanco AlonsoHospital Universitario Marqués de Valdecilla, IDIVAL, Universidad de Cantabria, Santander, Spain.
Alfonso Corrales MartínezHospital Universitario Marqués de Valdecilla, IDIVAL, Universidad de Cantabria, Santander, Spain.
Fernanda GenreHospital Universitario Marqués de Valdecilla, IDIVAL, Universidad de Cantabria, Santander, Spain.
Raquel López MejíasHospital Universitario Marqués de Valdecilla, IDIVAL, Universidad de Cantabria, Santander, Spain.
Miguel A Gonzalez-GayHospital Universitario Marqués de Valdecilla, IDIVAL, Universidad de Cantabria, Santander, Spain.ORCID 0000-0002-7924-7406
Sara RemuzgoHospital Universitario Marqués de Valdecilla, IDIVAL, Universidad de Cantabria, Santander, Spain.
Begoña Ubilla GarciaHospital Universitario Marqués de Valdecilla, IDIVAL, Universidad de Cantabria, Santander, Spain.
Ricard CerveraHospital Clínic and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Gerard EspinosaHospital Clínic and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Ignasi Rodríguez-PintóHospital Clínic and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Ellen De LangheKatholieke Universiteit Leuven and Universitair Ziekenhuis Leuven, Leuven, Belgium.
Jonathan CremerKatholieke Universiteit Leuven and Universitair Ziekenhuis Leuven, Leuven, Belgium.
Rik LoriesKatholieke Universiteit Leuven and Universitair Ziekenhuis Leuven, Leuven, Belgium.
Doreen BelzKlinikum der Universitaet zu Koeln, Cologne, Germany.
Nicolas HunzelmannKlinikum der Universitaet zu Koeln, Cologne, Germany.
Niklas BaerleckenHannover Medical School, Hannover, Germany.
Katja KnieschHannover Medical School, Hannover, Germany.
Torsten WitteHannover Medical School, Hannover, Germany.
Michaela LehnerMedical University Vienna, Vienna, Austria.
Georg StummvollMedical University Vienna, Vienna, Austria.
Michael ZaunerMedical University Vienna, Vienna, Austria.
Maria Angeles Aguirre-ZamoranoReina Sofia University Hospital and University of Cordoba, Cordoba, Spain.
Nuria BarbarrojaReina Sofia University Hospital and University of Cordoba, Cordoba, Spain.
Maria Carmen Castro-VillegasReina Sofia University Hospital and University of Cordoba, Cordoba, Spain.
Eduardo Collantes-EstevezReina Sofia University Hospital and University of Cordoba, Cordoba, Spain.
Enrique de RamonHospital Regional Universitario de Málaga, Málaga, Spain.
Isabel Díaz QuinteroHospital Regional Universitario de Málaga, Málaga, Spain.
Alejandro Escudero-ContrerasReina Sofia University Hospital and University of Cordoba, Cordoba, Spain.
María Concepción Fernández RoldánHospital Universitario San Cecilio, Granada, Spain.
Yolanda Jiménez GómezReina Sofia University Hospital and University of Cordoba, Cordoba, Spain.ORCID 0000-0002-1607-2717
Inmaculada Jiménez MoleónHospital Virgen de las Nieves, Granada, Spain.
Rosario Lopez-PedreraReina Sofia University Hospital and University of Cordoba, Cordoba, Spain.
Rafaela Ortega-CastroReina Sofia University Hospital and University of Cordoba, Cordoba, Spain.ORCID 0000-0002-7552-3469
Norberto OrtegoHospital Universitario San Cecilio, Granada, Spain.
Enrique RayaHospital Virgen de las Nieves, Granada, Spain.
Carolina ArtusiUniversità degli Studi di Milano, Milan, Italy.
Maria GerosaUniversità degli Studi di Milano, Milan, Italy.
Pier Luigi MeroniUniversità degli Studi di Milano, Milan, Italy.
Tommaso SchioppoUniversità degli Studi di Milano, Milan, Italy.
Aurélie De GroofUniversité Catholique de Louvain and Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Julie DucreuxUniversité Catholique de Louvain and Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Bernard LauwerysUniversité Catholique de Louvain and Cliniques Universitaires Saint-Luc, Brussels, Belgium.ORCID 0000-0003-3243-6151
Anne-Lise MaudouxUniversité Catholique de Louvain and Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Divi CornecUniversité de Brest, Centre Hospitalier Universitaire de Brest, INSERM, and Labex IGO, Brest, France.ORCID 0000-0002-9159-702X
Valérie Devauchelle-PensecUniversité de Brest, Centre Hospitalier Universitaire de Brest, INSERM, and Labex IGO, Brest, France.ORCID 0000-0003-0432-825X
Sandrine Jousse-JoulinUniversité de Brest, Centre Hospitalier Universitaire de Brest, INSERM, and Labex IGO, Brest, France.
Pierre-Emmanuel JouveAltraBio, Lyon, France.
Bénédicte RouvièreUniversité de Brest, Centre Hospitalier Universitaire de Brest, INSERM, and Labex IGO, Brest, France.
Alain SarauxUniversité de Brest, Centre Hospitalier Universitaire de Brest, INSERM, and Labex IGO, Brest, France.ORCID 0000-0002-8454-7067
Quentin SimonUniversité de Brest, Centre Hospitalier Universitaire de Brest, INSERM, and Labex IGO, Brest, France.
Montserrat AlvarezGeneva University Hospital, Geneva, Switzerland.
Carlo ChizzoliniGeneva University Hospital, Geneva, Switzerland.ORCID 0000-0003-4849-6335
Aleksandra DufourGeneva University Hospital, Geneva, Switzerland.
Donatienne WynarGeneva University Hospital, Geneva, Switzerland.
Attila BalogUniversity of Szeged, Szeged, Hungary.
Márta BocskaiUniversity of Szeged, Szeged, Hungary.
Magdolna DeákUniversity of Szeged, Szeged, Hungary.
Sonja DulicUniversity of Szeged, Szeged, Hungary.
Gabriella KádárUniversity of Szeged, Szeged, Hungary.
László KovácsUniversity of Szeged, Szeged, Hungary.
Qingyu ChengCharité Universitätsmedizin Berlin, Berlin, Germany.
Velia GerlCharité Universitätsmedizin Berlin, Berlin, Germany.
Falk HiepeCharité Universitätsmedizin Berlin, Berlin, Germany.
Laleh KhodadadiCharité Universitätsmedizin Berlin, Berlin, Germany.
Silvia ThielCharité Universitätsmedizin Berlin, Berlin, Germany.
Emanuele de RinaldisSanofi, Cambridge, Massachusetts.
Sambasiva RaoSanofi-Genzyme, Framingham, Massachusetts.
Robert J BenschopEli Lilly, Indianapolis, Indiana.
Chris ChamberlainUCB, Slough, UK.
Ernst R DowEli Lilly, Indianapolis, Indiana.
Yiannis IoannouUCB, Slough, UK.
Laurence LaigleInstitut de Recherches Internationales Servier, Suresnes, France.
Jacqueline MarovacUCB, Slough, UK.
Jerome WojcikQuartzBio, Geneva, Switzerland.
Yves RenaudineauUniversité de Brest, Centre Hospitalier Universitaire de Brest, INSERM, and Labex IGO, Brest, France.
Maria Orietta BorghiUniversità degli Studi di Milano and Istituto Auxologico Italiano, Milan, Italy.
Johan FrostegårdKarolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-3569-3367
Javier MartínInstitute of Parasitology and Biomedicine "López Neyra", Spanish National Research Council, Granada, Spain.
Lorenzo BerettaFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.ORCID 0000-0002-6529-6258
Esteban BallestarBellvitge Biomedical Research Institute, Barcelona, Spain.
Fiona McDonaldBayer, Berlin, Germany.
Jacques-Olivier PersUniversité de Brest, Centre Hospitalier Universitaire de Brest, INSERM, and Labex IGO, Brest, France.
Marta E Alarcón-RiquelmePfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research, Granada, Spain, and Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-7632-4154
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveClinical 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.
methodsUnsupervised 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.
resultsFour 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.
conclusionPatients 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.
Indexed as
EpigenomeGene Expression ProfilingAdultAgedAntiphospholipid SyndromeArthritis, RheumatoidAutoimmune DiseasesCase-Control StudiesCluster AnalysisCross-Sectional StudiesEpigenomicsFemaleHumansInflammationInterferonsLupus Erythematosus, SystemicInterferons
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