{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T06:24:24Z","timestamp":1786947864012,"version":"build-2736575974"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001664","name":"Leibniz-Gemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001664","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018693","name":"HORIZON EUROPE Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018693","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100022558","name":"Deutsches Rheuma-Forschungszentrum, Leibniz-Gemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022558","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Systemic lupus erythematosus (SLE) and other chronic inflammatory diseases are complex, multifactorial conditions where patient heterogeneity poses a major challenge to treatment. Despite the availability of numerous omics technologies, reliable biomarkers for precision medicine remain scarce, and many cell-based approaches are difficult to integrate into clinical settings. In this proof-of-concept study, we hypothesized that interrogating the cells\u2019 imprinting by the inflammatory environment through Unperturbed Activation Profiling (UACT) without prior restimulation would allow for the assessment of individual immune status in chronic rheumatic diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a highly standardized mass cytometry-based workflow to assess signaling protein phosphorylation in peripheral blood leukocytes from active SLE patients (n=20) and healthy controls (n=20) at the single-cell level. Importantly, the entire workflow from blood drawing to stabilization and preparation of barcoded samples was optimized to ensure necessary robustness of the procedure for clinical studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified leukocyte-specific in vivo-like signaling patterns in line with type I interferon-driven signatures, such as elevated pSTAT1 in na\u00efve T cells and pSTAT3 in classical monocytes and na\u00efve CD8 T cells. These patterns captured patient variability and immune activation, although they did not correlate with SLEDAI-2K disease activity scores. We further explored the utility of UACT for treatment monitoring in four SLE patients treated with the JAK inhibitor baricitinib under compassionate use, where baseline pSTAT3 levels across multiple cell subsets seemed to be associated with treatment response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our results thus demonstrate that single-cell UACT without restimulation of cells can detect immune activation in chronic inflammatory diseases, supporting both biomarker discovery and the identification of novel therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1844288","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T05:26:27Z","timestamp":1786944387000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Single-cell Unperturbed Activation Profiling by mass cytometry captures in vivo immune signaling in SLE"],"prefix":"10.3389","volume":"17","author":[{"given":"Marie","family":"Burns","sequence":"first","affiliation":[{"name":"German Rheumatology Research Center (DRFZ), An Institute of the Leibniz Association","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lennard","family":"Ostendorf","sequence":"additional","affiliation":[{"name":"German Rheumatology Research Center (DRFZ), An Institute of the Leibniz Association","place":["Berlin, Germany"]},{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amro","family":"Abbas","sequence":"additional","affiliation":[{"name":"German Rheumatology Research Center (DRFZ), An Institute of the Leibniz Association","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Ferrara","sequence":"additional","affiliation":[{"name":"German Rheumatology Research Center (DRFZ), An Institute of the Leibniz Association","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Hirseland","sequence":"additional","affiliation":[{"name":"German Rheumatology Research Center (DRFZ), An Institute of the Leibniz Association","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Baumgart","sequence":"additional","affiliation":[{"name":"German Rheumatology Research Center (DRFZ), An Institute of the Leibniz Association","place":["Berlin, Germany"]},{"name":"Institute of Immunology, Core Facility Cytometry, Jena University Hospital, Friedrich-Schiller-University","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Barreno-Sanchez","sequence":"additional","affiliation":[{"name":"German Rheumatology Research Center (DRFZ), An Institute of the Leibniz Association","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Frischbutter","sequence":"additional","affiliation":[{"name":"Institute of Allergology, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, Campus Benjamin Franklin Berlin","place":["Berlin, Germany"]},{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Alexander","sequence":"additional","affiliation":[{"name":"German Rheumatology Research Center (DRFZ), An Institute of the Leibniz Association","place":["Berlin, Germany"]},{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Biesen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik E.","family":"Mei","sequence":"additional","affiliation":[{"name":"German Rheumatology Research Center (DRFZ), An Institute of the Leibniz Association","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Gr\u00fctzkau","sequence":"additional","affiliation":[{"name":"German Rheumatology Research Center (DRFZ), An Institute of the Leibniz Association","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel R.","family":"Schulz","sequence":"additional","affiliation":[{"name":"German Rheumatology Research Center (DRFZ), An Institute of the Leibniz Association","place":["Berlin, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-212565","article-title":"Common language description of the term rheumatic and musculoskeletal diseases (RMDs) for use in communication with the lay public, healthcare providers and other stakeholders endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR)","volume":"77","author":"Van Der Heijde","year":"2018","journal-title":"Ann Rheum Dis"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780340802","article-title":"Definition, incidence, and clinical description of flare in systemic lupus erythematosus. 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