{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:07:00Z","timestamp":1787314020360,"version":"build-2736575974"},"reference-count":34,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"unspecified","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32141004"],"award-info":[{"award-number":["32141004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["9237420006"],"award-info":[{"award-number":["9237420006"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Lupus Sci Med"],"accepted":{"date-parts":[[2026,2,28]]},"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study explored the relationship between clinical phenotypes and immuno-molecular features of systemic lupus erythematosus (SLE) using unsupervised machine learning and multi-omics integration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A multicentre cohort of 1065 SLE patients from five teaching hospitals was studied. Unsupervised clustering was performed using integrated clinical and laboratory data to identify distinct phenotypic clusters. Multi-omics profiling, including proteomics and transcriptomics, was conducted for each cluster, comparing with healthy controls. In addition, 899 patients were prospectively followed for over 1 year to assess therapeutic responses and remission outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Unsupervised clustering identified five distinct clusters of SLE based on clinical phenotypes and immunological signatures, and an intrinsic association was found between each cluster and immune-inflammatory features. Cluster 1 (renal; 14.27%) had predominant renal involvement (87.5%) and high disease activity. Cluster 2 (mucocutaneous; 39.53%) exhibited mainly cutaneous manifestations (72.45%) with mild visceral involvement and the highest rates of achieving low disease activity state (46.42%). Cluster 3 (neuropsychiatric; 14.74%) had a high frequency of neuropsychiatric manifestations (96.18%) and anti-U1 ribonucleoprotein antibodies positivity (42.04%). Cluster 4 (haematologic; 22.63%) was characterised by haematologic involvement, predominantly cytopenia (95.85%), with frequent antiphospholipid antibody positivity and direct Coombs positivity (87.55%). Cluster 5 (cardiopulmonary; 8.83%) exhibited prominent cardiopulmonary involvement (97.87%) and serositis, with enrichment of inflammatory CD161\n                      <jats:sup>+<\/jats:sup>\n                      regulatory T cells. Transcriptomic and proteomic analyses confirmed distinct molecular signatures and cluster-specific enrichment of biological pathways. Key molecule apolipoprotein A4 was validated using enzyme-linked immunosorbent assay. Regarding therapeutic outcomes at 1\u2009year follow-up, Cluster 2 had the highest proportions achieving lupus low disease activity state (46.42%) and tapering glucocorticoids. Cyclophosphamide use was associated with greater clinical improvement (r=0.284; p=0.023) in Cluster 3, while in Cluster 5, rituximab use was associated with favourable responses (r=0.286; p=0.019).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We identified five SLE clusters with distinct clinical, immunological features and treatment outcomes, demonstrating an intrinsic link between clinical involvement and immune-inflammatory alterations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/lupus-2025-001842","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T11:00:23Z","timestamp":1775646023000},"page":"e001842","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Unsupervised clustering of clinical and laboratory features of systemic lupus erythematosus: insights from a multicentre cohort"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2887-4116","authenticated-orcid":false,"given":"Yuke","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Peking University People\u2019s Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Peking University People\u2019s Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Peking University People\u2019s Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghua","family":"Chen","sequence":"additional","affiliation":[{"name":"Jinling Hospital National Clinical Research Center of Kidney Diseases, Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghua","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyuan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Peking University People\u2019s Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujia","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Peking University People\u2019s Hospital, Beijing, 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