ArticleArthritis care & research2026
Serum Soluble Mediator Signatures of Lupus Nephritis: Histologic Features and Response to Treatment.
Article in Arthritis care & research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Tailoring KDIGO guidelines for lupus nephritis to the real world: a stratified and cost-aware approach.Clinical kidney journal · 2026Review
- Autoantibody repertoire in lupus nephritis: from pathogenic mechanisms to clinical integration for precision decision-making.Frontiers in immunology · 2026Review
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27 authors.
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Abstract
objectiveLupus 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.
methodsPatients 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.
resultsProliferative 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 predictive of proliferative LN (areas under the curve, 0.82; 95% confidence interval [CI], 0.81-0.91), including elevated syndecan-1, tumor necrosis factor receptor type I, tumor necrosis factor receptor type II, and vascular cell adhesion molecule 1 (VCAM-1), as well as decreased CCL3//macrophage inflammatory protein 1α, CD40 ligand, and interleukin-5 levels. Among proliferative patients with LN, 3-month reductions in syndecan-1 and VCAM-1, mediators associated with intrarenal LN activity and/or chronicity, predicted the 12-month treatment response. A model incorporated these reductions and a decline in UPCR-predicted treatment response in proliferative LN (0.90; 95% CI, 0.82-0.98). Molecular clustering revealed four distinct LN subgroups with unique soluble mediator signatures and clinical features not captured by histology alone.
conclusionSerum soluble mediators, particularly syndecan-1 and VCAM-1, reflect LN histologic activity, and early decreases predict treatment response, supporting their potential use as noninvasive longitudinal biomarkers. The substantial heterogeneity within LN highlights the potential for biomarker-guided reclassification to advance precision medicine approaches.
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