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

Tianyu Zheng1, Yuanyuan Du2, Xuanli Tang2

  • 1College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China.

Nephron
|January 6, 2026
PubMed
Abstract

Insights

Soluble T-cell immunoglobulin and mucin-domain containing-3 (sTim-3) combined with M-type phospholipase A2 receptor antibody (PLA2R-Ab) improves risk stratification in membranous nephropathy. This combination accurately predicts treatment outcomes and identifies patients needing intensive immunosuppression.

Area of Science:

  • Nephrology
  • Immunology
  • Biomarker Discovery

Background:

  • M-type phospholipase A2 receptor antibody (PLA2R-Ab) utility for risk stratification in membranous nephropathy (MN) is suboptimal.
  • Soluble T-cell immunoglobulin and mucin-domain containing-3 (sTim-3) is a critical immune regulator in kidney diseases.
  • This study investigates the prognostic value of sTim-3 in PLA2R-associated MN (PMN) and its combination with PLA2R-Ab.

Purpose of the Study:

  • To evaluate the prognostic value of sTim-3 in PLA2R-associated MN (PMN).
  • To assess the efficacy of combining sTim-3 with PLA2R-Ab for risk stratification in PMN.
  • To identify optimal cut-off values for sTim-3 and PLA2R-Ab in predicting treatment outcomes.

Main Methods:

  • Serum PLA2R-Ab and sTim-3 levels were measured at baseline in 50 PMN patients.
  • Highly sensitive time-resolved fluorescence immunoassay (TRFIA) was used for quantification.
  • Patients were stratified into complete remission (CR), partial remission (PR), and no remission (NR) groups based on 12-month outcomes.

Main Results:

  • Prognostic cut-offs were identified: sTim-3 = 17.63 ng/mL and PLA2R-Ab = 50 RU/mL (KDIGO high-risk).
  • The combination of sTim-3 and PLA2R-Ab achieved a 0% non-remission rate, compared to 23.58% for PLA2R-Ab < 50 RU/mL alone.
  • Double positivity (PLA2R-Ab > 50 RU/mL and sTim-3 > 17.63 ng/mL) identified a refractory subgroup with poorer treatment response.

Conclusions:

  • sTim-3 serves as a complementary biomarker to PLA2R-Ab for risk stratification in PMN.
  • Combined detection optimizes risk stratification, guiding intensive immunosuppression for high-risk patients.
  • This approach helps prevent overtreatment in PLA2R-Ab-high patients with favorable immune status.
Keywords:
M-type phospholipase A2 receptor antibodyMembranous nephropathyPrognosis predictionT-cell immunoglobulin and mucin-domain molecule 3

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