{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T07:09:56Z","timestamp":1773644996574,"version":"3.50.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Childhood-onset systemic lupus erythematosus (cSLE) exhibits significant heterogeneity, leading to challenges in prognosis and treatment. This study aims to stratify cSLE patients into clinically distinct subgroups based on routine autoantibody profiles and to characterize these subgroups by their differences in\n                      <jats:italic>HLA-DRB1<\/jats:italic>\n                      genotypes, cytokine signatures, clinical manifestations, and flare incidence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a retrospective study of 102 cSLE patients. An unsupervised two-step cluster analysis was performed using nine routinely measured autoantibodies. The resulting subgroups were compared for clinical features,\n                      <jats:italic>HLA-DRB1<\/jats:italic>\n                      allele frequencies, serum cytokine levels, and flare-free survival using Kaplan\u2013Meier analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Cluster analysis identified two distinct subgroups. Subgroup 2, characterized by anti-Sm\/RNP positivity, demonstrated significantly more severe disease, including higher rates of lupus nephritis, neuropsychiatric involvement, and elevated SLE disease activity index (SLEDAI) scores at diagnosis compared to subgroup 1 (anti-Sm\/RNP-negative). Genetically, subgroup 2 was enriched with the\n                      <jats:italic>HLA-DRB1*15<\/jats:italic>\n                      and *\n                      <jats:italic>09<\/jats:italic>\n                      alleles. Immunologically, subgroup 2 exhibited significantly elevated IFN-\u03b1 levels. Despite more frequent use of belimumab, subgroup 2 had a significantly lower flare-free survival rate than subgroup 1 (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Autoantibody-based stratification effectively delineates two cSLE subgroups with distinct genetic, immunological, and clinical trajectories. The anti-Sm\/RNP positive subgroup, defined by\n                      <jats:italic>HLA-DRB1*15\/09<\/jats:italic>\n                      risk alleles and a high IFN-\u03b1 signature, represents a more severe phenotype with a higher risk of flare, potentially explaining the suboptimal response to belimumab in this group.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1766478","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T06:37:23Z","timestamp":1773643043000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Subgroups based on autoantibody status associated with clinical manifestations, HLA-DRB1 variants, cytokines, and flare of vasculitis in childhood-onset systemic lupus erythematosus"],"prefix":"10.3389","volume":"17","author":[{"given":"Shengfang","family":"Bao","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]},{"name":"Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiani","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingying","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuemei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenxi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiqiong","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Rheumatology and Immunology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanliang","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Shanghai Children\u2019s Medical Center, School of Medicine, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/s41392-025-02168-0","article-title":"Systemic lupus erythematosus: updated insights on the pathogenesis, diagnosis, prevention and therapeutics","volume":"10","author":"Dai","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"B2","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1002\/acr2.11343","article-title":"Four systemic lupus erythematosus subgroups, defined by autoantibodies status, differ regarding HLA-DRB1 genotype associations and 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