期刊
NEPHROLOGY DIALYSIS TRANSPLANTATION
卷 33, 期 5, 页码 832-840出版社
OXFORD UNIV PRESS
DOI: 10.1093/ndt/gfx235
关键词
complement; IgG subclass; mannose-binding lectin; PLA2R; THSD7A
资金
- Japan Society for the Promotion of Science [25461237, 2530502]
- Ministry of Health, Labour, and Welfare of Japan
- Grants-in-Aid for Scientific Research [25461237] Funding Source: KAKEN
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 Japanese 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 (65%) patients had PLA2R in glomerular deposits and two (33%) patients 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 were much higher in the intrinsic antigen-related group [55% versus 20%, P < 0.010, 1.0 (interquartile range 1.0-2.0) versus 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 [hazard ratio (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. Conclusions. Intrinsic antigen-related MN was more strongly associated with complement activation by the lectin pathway, which may contribute to a less favorable clinical outcome.
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