Integrated sTim-3 and PLA2R-Ab Levels Improve Risk Stratification in PLA2R-Positive Membranous Nephropathy

BACKGROUND The utility of M-type phospholipase A2 receptor antibody (PLA2R-Ab) for risk stratification in membranous nephropathy (MN) remains suboptimal, while soluble T-cell immunoglobulin and mucin-domain containing-3 (sTim-3) has confirmed as a critical immune regulator in kidney diseases. This study investigated the outcome prognostic value of sTim-3 in PLA2R associated MN (PMN) and the efficacy of its combination with PLA2R-Ab.

METHODS Serum PLA2R-Ab and sTim-3 levels were measured at baseline in 50 PMN patients using highly sensitive time-resolved fluorescence immunoassay (TRFIA) method. Patients were stratified into complete remission (CR), partial remission (PR), and no remission (NR) groups according to 12-month treatment outcomes.

RESULTS Prognostic cut-off discriminating NR from remission: sTim-3=17.63 ng/mL; PLA2R-Ab=50 RU/mL (KDIGO high-risk threshold). The non-remission rate of for PLA2R-Ab<50 RU/mL in PMN patients was 23.58%, whereas the sTim-3+PLA2R-Ab combination achieved 0%. Among 16 "high-risk" patients (PLA2R-Ab>50 RU/mL), sTim-3 demonstrated 93.75% accuracy in predicting outcomes. Remarkably, all 8 patients who achieved actual remission exhibited sTim-3 levels below 17.63 ng/mL. Double positivity (PLA2R-Ab>50 RU/mL and sTim-3>17.63 ng/mL) identified a refractory subgroup with significantly poorer treatment response.

CONCLUSION sTim-3 serves as a complementary biomarker to PLA2R-Ab. Combined detection optimizes PMN risk stratification: PLA2R-Ab>50 RU/mL and sTim-3>17.63 ng/mL indicates an immune-activated state requiring intensive immunosuppression, preventing overtreatment in PLA2R-Ab-high patients with favorable immune status.