Serum RNASE1 as a biomarker for disease activity and lupus nephritis in systemic lupus erythematosus

Introduction: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by autoantibody production and immune complex-mediated organ damage, frequently involving the kidneys as lupus nephritis (LN). However, reliable blood-based biomarkers for disease activity and renal involvement remain limited. Methods: We performed serum proteomic profiling in newly diagnosed SLE patients and integrated these data with renal transcriptomic datasets from SLE mouse models to identify candidate biomarkers. Associations between serum RNASE1 levels and clinical parameters were evaluated, and a composite RNASE1-albumin-calcium (RAC) score was developed. Results: RNASE1 was consistently upregulated in both serum and renal tissues of SLE patients. Serum RNASE1 levels were significantly elevated compared with healthy controls and showed positive correlations with proteinuria and SLE Disease Activity Index (SLEDAI) scores, and a negative correlation with complement C3. The RAC score demonstrated stronger correlations with disease activity and renal function than RNASE1 alone. Receiver operating characteristic (ROC) analysis showed that the RAC score discriminated SLE disease activity with area under the curve (AUC) values of 0.7654, 0.7737, and 0.8072 for ≥mild, ≥moderate, and ≥severe activity, respectively. In addition, renal RNASE1 expression increased with LN severity and was significantly higher in class IV ± V LN than in class III ± V or class V LN, correlating with the pathological activity index. Discussion: RNASE1 is a promising biomarker reflecting both systemic disease activity and renal involvement in SLE. The RNASE1-based RAC score provides a noninvasive tool for improved disease assessment and may facilitate clinical monitoring and management of SLE patients.