Lupus nephritis (LN), occurring in approximately 50% of individuals with systemic lupus erythematosus (SLE), significantly influences therapy and prognosis. Proliferative LN, more prevalent than non-proliferative LN, is associated with a poorer prognosis. This study aimed to investigate the potential correlation between serum levels of the pro-inflammatory proteins human calcium-binding S100P (S100P) and Human complement Fragment 4 (C4d) and confirmed proliferative LN through biopsy. The objective was to evaluate their reliability as biomarkers for disease activity in proliferative LN.
 Methods. Serum S100P and C4d were measured using enzyme-linked immunosorbent assay in 100 female patients with established SLE. Among these, 50 had confirmed proliferative LN through biopsy, and 50 did not. A control group of 50 healthy female donors' plasma samples was included.
 Results. SLE patients with proliferative LN exhibited significantly higher serum levels of S100P (P < 0.001) and C4d (P < 0.001) compared to SLE patients without LN and controls. Serum S100P demonstrated a significantly higher positive correlation with the activity index in renal biopsies (r = 0.784) compared to serum C4d (r = 0.416). Additionally, serum S100P had a significantly higher positive correlation with SLEDAI-R than serum C4d (r = 0.651 vs. r = 0.257). Both serum S100P and C4d showed promise as reliable biomarkers for the diagnosis of active proliferative LN, as indicated by the ROC curve and AUC assessments.
 Conclusion. Serum concentrations of S100P and C4d emerge as useful indicators for identifying SLE patients with active proliferative LN.