{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:24:40Z","timestamp":1792448680080,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ACR Open Rheumatology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Systemic lupus erythematosus (SLE) is biologically heterogeneous, motivating development of reproducible molecular subtypes that can track change over time. The aim of this study was to establish a reproducible molecular stratification of SLE across cohorts and platforms and connect the resulting subtypes to clinical activity, serology, and serum proteomics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We computed Gene Set Variation Analysis scores for eight immune gene modules from baseline transcriptomes (ILLUMINATE whole\u2010blood microarray [N\u00a0=\u00a01,756], LOTUS whole\u2010blood RNA sequencing [RNA\u2010seq; N\u00a0=\u00a0585], and Genuity peripheral blood mononuclear cell (PBMC) RNA\u2010seq [N\u00a0=\u00a0812]). We clustered ILLUMINATE patients (K\u00a0=\u00a02\u20138) and selected K\u00a0=\u00a06, then used a random forest classifier to assign subtypes in LOTUS and Genuity. We analyzed serum proteomics (SomaScan in LOTUS; Olink in Genuity), assessed glucocorticoid associations with neutrophil modules, and quantified baseline to week 24 stability in LOTUS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Six molecular subtypes replicated across cohorts and corresponded to different levels of disease activity and serology (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). Proteomic patterns converged with transcriptomics, with concordant differential proteins across Olink and SomaScan among shared targets. Neutrophils were a key axis: one neutrophil module tracked glucocorticoid use, whereas a second was glucocorticoid independent. In LOTUS, subtype assignments were mostly stable to week 24; when patients moved, transitions were nonrandom, occurred between adjacent subtypes, and were similar in the placebo group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We demonstrated reproducible SLE molecular subtypes (interferon, plasmablast\/B cell, neutrophil) supported by independent proteomics. In LOTUS, subtypes were largely stable through week 24. When patients changed subtypes, transitions followed preferential trajectories, supporting longitudinal tracking and trial design utility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acr2.90083","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T05:33:06Z","timestamp":1783143186000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Reproducible Molecular Subtypes in Systemic Lupus Erythematosus Are Associated With Disease Activity, Serology, and Distinct Trajectories Over Time"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7028-3024","authenticated-orcid":false,"given":"Loqmane","family":"Seridi","sequence":"first","affiliation":[{"name":"Immunology, Johnson &amp; Johnson  Spring House Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Myshkin","sequence":"additional","affiliation":[{"name":"Immunology, Johnson &amp; Johnson  Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5712-3579","authenticated-orcid":false,"given":"Erika","family":"Noss","sequence":"additional","affiliation":[{"name":"Immunology, Johnson &amp; Johnson  Spring House Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Gao","sequence":"additional","affiliation":[{"name":"Immunology, Johnson &amp; Johnson  Spring House Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Molineros","sequence":"additional","affiliation":[{"name":"Data Science and Digital Health, Johnson &amp; Johnson  Spring House Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Cuff","sequence":"additional","affiliation":[{"name":"Immunology, Johnson &amp; Johnson  Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn","family":"Waterworth","sequence":"additional","affiliation":[{"name":"Immunology, Johnson &amp; Johnson  Spring House Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8609-118X","authenticated-orcid":false,"given":"Matthew J.","family":"Loza","sequence":"additional","affiliation":[{"name":"Immunology, Johnson &amp; Johnson  Spring House Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-023-01237-9"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38628"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.03.008"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.07.021"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2020.10.014"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052505"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-018-0468-1"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2023.103025"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-024-01210-9"},{"issue":"10","key":"e_1_2_8_11_1","first-page":"10681","article-title":"Serum 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