Abstract: TH-PO109

Clinical Impact of Glomerular Mannose-Binding Lectin Deposition in Intrinsic Antigen-Related Membranous Nephropathy

Session Information

Category: Glomerular

  • 1004 Clinical/Diagnostic Renal Pathology and Lab Medicine

Authors

  • Hayashi, Norifumi, Kanazawa Medical University, Kanazawa, Japan
  • Matsui, Yuki, Kanazawa Medical University, Kanazawa, Japan
  • Fujimoto, Keiji, Kanazawa Medical University, Kanazawa, Japan
  • Adachi, Hiroki, Kanazawa medical university, Kanazawa, Japan
  • Yamaya, Hideki, Kanazawa Medical University, Kanazawa, Japan
  • Yokoyama, Hitoshi, Kanazawa Medical University, Kanazawa, Japan
Background

The M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) were identified as intrinsic antigens in primary membranous nephropathy (MN). Complement activation via the lectin pathway in intrinsic antigen-related MN is still unclear.

Methods

We retrospectively enrolled 60 primary MN patients and detected activated complement pathways by staining complement proteins in glomerular deposition. According to the findings of PLA2R and THSD7A staining in glomeruli, they were classified into intrinsic antigen-related or -unrelated MN. We evaluated clinicopathological characteristics and predictors of clinical outcomes in intrinsic antigen-related MN.

Results

Thirty-nine patients (65%) had PLA2R in glomerular deposits and 2 patients (3.3%) had THSD7A. One of them had both PLA2R and THSD7A (double positive). Forty patients were classified into the intrinsic antigen-related group. The other 20 patients were negative for both antigens (unrelated group). The prevalence and staining intensity of mannose-binding lectin (MBL) deposits was much higher in the intrinsic antigen-related group (55% vs. 20%, P<0.010, 1.0 [1.0-2.0] vs. 1.0 [0.0-1.0], p=0.01, respectively). The staining intensity of MBL in glomeruli also correlated with the IgG4 staining intensity. In intrinsic antigen-related MN, MBL staining intensity was an unfavorable predictor for remission of proteinuria (HR 0.40, p<0.01) and renal dysfunction (HR 3.81, p=0.01) in Cox proportional hazards analysis. Moreover, the glomerular MBL-positive group showed more severe interstitial fibrosis and worse clinical outcomes.

Conclusion

Intrinsic antigen-related MN was more strongly associated with complement activation by the lectin pathway, and was an unfavorable predictor for clinical outcomes.