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While renal immune perturbations are well-studied, systemic signatures specific to LN pathogenesis remain unclear. Integrated single-cell RNA and immune repertoire analysis of 177,259 peripheral blood mononuclear cells (PBMCs) from healthy donors and SLE patients (including active LN and non-nephritis controls) revealed LN-specific circulating immune signatures, including \u03ba light-chain preference in naive B cells and distinct clonal expansion in CD8\n                    <jats:sup>+<\/jats:sup>\n                    effector T cells. These clonally expanded CD8\n                    <jats:sup>+<\/jats:sup>\n                    effector T cells exhibited transcriptional variations indicating increased migratory capacity and exhaustion, along with preferential usage of TRBV genes (\n                    <jats:italic>TRBV27\/TRBV15\/TRBV7-9<\/jats:italic>\n                    ), which have enhanced binding potential to an EBV epitope GLCTLVAM. Based on these findings, we developed a dual-biomarker model demonstrating reliable LN diagnosis (AUC\u2009=\u20090.895). Cross-tissue analysis confirmed concordance between peripheral and intrarenal immune perturbations, supporting non-invasive blood-based monitoring. Enhanced MIF-(CD74\u2009+\u2009CXCR4) axis activity linked to lymphocyte activation\/migration, while CD74\n                    <jats:sup>+<\/jats:sup>\n                    memory B cells upregulated MHC-I antigen presentation. Renal immunostaining revealed CD74\n                    <jats:sup>+<\/jats:sup>\n                    B cells proximal to CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltrates, suggesting CD74-mediated crosstalk facilitates intrarenal T cell activation. This study provides an integrated LN immune atlas, identifies translatable biomarkers and highlights CD74 as a potential therapeutic target.\n                  <\/jats:p>","DOI":"10.1038\/s42003-025-09431-8","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T13:11:01Z","timestamp":1767618661000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Single-cell profiling unveils nephritis-related circulating immunological signatures in systemic lupus erythematosus patients"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6656-6415","authenticated-orcid":false,"given":"Qun","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9103-7719","authenticated-orcid":false,"given":"Linjie","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyao","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunlai","family":"Shang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yena","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinggang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5330-1040","authenticated-orcid":false,"given":"Ping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9536-287X","authenticated-orcid":false,"given":"Xueyuan","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaomin","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuyang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huayu","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyan","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8774-6021","authenticated-orcid":false,"given":"Xiangmei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"9431_CR1","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/j.cell.2016.03.008","volume":"165","author":"R Banchereau","year":"2016","unstructured":"Banchereau, R. et al. 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