Serum Soluble Mediator Signatures of Lupus Nephritis: Histologic Features and Response to Treatment

作者：Andrea Fava, Catriona A. Wagner, Carla Guthridge, Susan Macwana, Wade DeJager, Melissa E. Munroe, Peter Izmirly, H. Michael Belmont, Betty Diamond, Anne Davidson, Paul J. Utz, Michael H. Weisman, Philip M. Carlucci, Maria Dall’Era, Kenneth Kalunian, Chaim Putterman, Jennifer H. Anolik, Jennifer L. Barnas, David Wofsy, Diane L. Kamen, Richard Furie, Deepak A. Rao, the Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus Network, Michelle Petri, Joel M. Guthridge, Jill P. Buyon, Judith A. James · 发表于：Arthritis Care & Research · 年份：2025 · DOI：10.1002/acr.25652 · 被引用次数：4 · 研究领域：Systemic Lupus Erythematosus Research、Chemokine receptors and signaling、Multiple Sclerosis Research Studies

OBJECTIVE: Lupus nephritis (LN) management remains challenging, and novel noninvasive biomarkers are needed. This study quantified serum soluble mediators in the Accelerating Medicines Partnership (AMP) LN cohort to identify biomarkers of histologic features and treatment response. METHODS: Patients with systemic lupus erythematosus (SLE) (n = 268) undergoing clinically indicated kidney biopsies (urine protein/creatinine ratio [UPCR] ≥ 0.5) were recruited through the AMP Rheumatoid Arthritis and SLE Network. Serum was collected at biopsy and 3-, 6-, and 12-month postbiopsy, alongside samples from 22 healthy controls. Concentrations of 66 immune mediators were quantified using xMAP multiplex assays, and (TACE) measured by enzyme-linked immunosorbent assay. Seven mediators with >95% values below detection limits were excluded from analyses. Bootstrapped least absolute shrinkage and selection operator (LASSO) regression identified proliferative LN (class III/IV ± V) predictors from baseline mediators. Associations with 12-month treatment response (complete/partial vs no response) were tested using three-month changes in LASSO-selected mediators and UPCR via logistic regression. Molecular clustering of mediator profiles was performed to identify LN subgroups. RESULTS: Proliferative patients with LN (class [III or IV] ± V; n = 160) displayed a distinct mediator profile compared with nonproliferative LN (class I, II, or V; n = 96). LASSO regression identified 20 mediators predictiv...