Mannose-Binding Lectin and Membranous Nephropathy

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Zhang Y, Liu Y, Liang L, Liu L, Tang X, Tang L, Chen P, Chen J, Wang Z, Cao W, Chen Q, Zhao N, Xu D: Effect of Glomerular Mannose-Binding Lectin Deposition on the Prognosis of Idiopathic Membranous Nephropathy. Kidney and Blood Pressure Research DOI 10.1159/000508665

Mannose-binding lectin (MBL), complement components 3 and 4d, IgG4 and PLA2R antigen (and/or thrombospondin 7A; THSD7A) are frequently co-deposited or hyperexpressed in the glomeruli of patients with primary membranous nephropathy (MN). Strong C4b and MBL depositions (indicative of activation of the lectin pathway of the complement cascade) have been linked to an adverse prognosis in IgA nephropathy, but this observation has not been extensively studied in MN.

Zhang and colleagues examined 67 Chinese subjects with presumed primary MN, 55% of whom were PLA2R antibody positive and 1.4% with combined PLA2R and THSD7A antibody. MBL deposition was present in 79% of these cases and PLA2R antigen hyperexpression was found in 73% of the cases. Unfortunately, no studies of C4d deposition were carried out. This magnitude of MBL deposition in primary MN has been previously reported. In this series MBL deposition was associated with a more favorable prognosis, as assessed by the frequency of a partial remission to proteinuria of >0.3 and <1.0 g/day, at least over the short-term follow-up. This finding was also present in a fully adjusted multivariate model.

Prior studies have suggested that MBL deposition is associated with a less favorable prognosis (similar to IgA nephropathy). The explanation for these discordant findings is not immediately apparent, but in the Zhang et al. study MBL deposition was correlated with tissue PLA2R antigen expression but not with circulating anti-PLA2R antibody levels. Interestingly, C1q deposition (by immunofluorescence microscopy) was found in 22% of the patients. IgG subclass 4 and C4d deposition was not studied, and both absences are weaknesses of this study. The putative “protective” role of glomerular deposition of MBL clearly needs further research.

Richard Glassock

Quoted Karger Article

Effect of Glomerular Mannose-Binding Lectin Deposition on the Prognosis of Idiopathic Membranous Nephropathy