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Here we construct a transcriptional patient map of SLE by analyzing 1,167 total samples (783 SLE, 384 healthy controls) across different resolutions, including single-cell and bulk blood as well as spatially resolved kidney tissue transcriptomes. Using an unsupervised approach we inferred patient-level transcriptomic immune programs from two independent single-cell RNA sequencing cohorts of peripheral blood mononuclear cells (PBMCs), capturing both differences between SLE and health as well as within-SLE heterogeneity. Specifically, we identified four conserved programs comprising two multicellular inflammatory programs driven by interferon and TNF\/NFkB activity across immune cells, and two cell type-specific programs reflecting CD8 T cell cytotoxicity and a CD4 T cell naive-to-effector state. Functional analysis of these programs revealed a rewiring of both cell-to-cell interactions and task allocation across cell types during disease activation. In addition, mapping these programs onto an external longitudinal blood transcriptomic cohort predicted flare risk and identified candidate blood protein biomarkers detectable by proteomics. Finally, we showed that these blood programs were enriched in immune-infiltrated glomerular regions from kidney biopsies of individuals with lupus nephritis using spatially resolved transcriptomic data, thereby linking systemic immune programs to local tissue pathology.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"721379v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                    <\/jats:fig>\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.28.721379","type":"posted-content","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T19:35:14Z","timestamp":1777664114000},"source":"Crossref","is-referenced-by-count":2,"title":["A transcriptional patient map of systemic lupus erythematosus reveals disease-related multicellular immune programs conserved between blood and kidney"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5454-1297","authenticated-orcid":false,"given":"Jose","family":"Li\u00f1ares-Blanco","sequence":"first","affiliation":[{"name":"European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridgeshire, U.K"},{"name":"Machine Learning lab in Life Sciences. Dept. of Computer Science and Information Technologies, Universidade da Coru\u00f1a (CITIC), A Coru\u00f1a, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4403-8592","authenticated-orcid":false,"given":"Philipp Sven Lars","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9338-4978","authenticated-orcid":false,"given":"Leoni","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2063-9744","authenticated-orcid":false,"given":"Ricardo","family":"Melo Ferreira","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8440-312X","authenticated-orcid":false,"given":"Daniel","family":"Toro Dominguez","sequence":"additional","affiliation":[{"name":"Unit of Inflammatory Diseases, Department of Environmental Medicine, Karolinska Institute, Nobel v\u00e4g 13, 171 67, Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6173-7255","authenticated-orcid":false,"given":"Pedro","family":"Carmona Saez","sequence":"additional","affiliation":[{"name":"Bioinformatics and Health Data Science. Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO). Granada, Spain"},{"name":"Department of Statistics and Operations Research. University of Granada. Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7177-1003","authenticated-orcid":false,"given":"Jovan","family":"Tanevski","sequence":"additional","affiliation":[{"name":"Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7632-4154","authenticated-orcid":false,"given":"Marta E.","family":"Alarcon Riquelme","sequence":"additional","affiliation":[{"name":"Unit of Inflammatory Diseases, Department of Environmental Medicine, Karolinska Institute, Nobel v\u00e4g 13, 171 67, Solna, Sweden"},{"name":"Genetics and Genomics of Immune-Mediated Diseases, Centro Pfizer \u2013 Universidad de Granada \u2013 Junta de Andaluc\u00eda de Gen\u00f3mica e Investigaci\u00f3n Oncol\u00f3gica (GENYO), Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3066-2876","authenticated-orcid":false,"given":"Michael T.","family":"Eadon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0087-371X","authenticated-orcid":false,"given":"Ricardo O.","family":"Ramirez Flores","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridgeshire, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8552-8976","authenticated-orcid":false,"given":"Julio","family":"Saez-Rodriguez","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridgeshire, U.K"},{"name":"Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026050517350574000_2026.04.28.721379v1.1","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/S0140-6736(13)61499-3","article-title":"Clinical aspects of autoimmune rheumatic diseases","volume":"382","year":"2013","journal-title":"Lancet Lond. 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