Membranous nephropathy: current understanding of various causes in light of new target antigens

Abstract

Purpose of review: Membranous nephropathy is an autoimmune disease caused by antibodies mostly directed to podocyte antigens. PLA2R and THSD7A antigens were described in 2009 and 2014 using classical immunochemical techniques. In the last 2 years, thanks to the combination of laser microdissection of glomeruli and mass spectrometry of solubilized digested proteins, several antigens associated with various causes have been described in patients with membranous nephropathy. The purpose of this review is to report on those "new" antigens and to analyse the clinicopathological correlations that make each of this antigen unique.

Recent findings: This article covers the literature of the last 2 years devoted to the description of those new antigens and biomarkers including NELL-1 and Semaphorin 3B in primary membranous nephropathy, and exostosins 1 and 2 and NCAM in lupus class V membranous nephropathy, which will be compared with the previously described antigens. These findings will lead to propose a new classification of membranous nephropathy based on serology and tissue antigen identification that could/should substitute for the classical distinction between primary and secondary membranous nephropathy.

Summary: The discovery of the latest antigens has major implications for the care of patients with membranous nephropathy as they drive the etiologic investigations and provide invaluable markers for treatment monitoring.

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FIGURE 1

Shows the presence of the four biomarker/antigens in immune deposits in membranous nephropathy. Note the granular aspect of the fluorescence on the outer aspect of the glomerular basement membrane. Neural cell adhesion molecule 1 (NCAM1) is adapted from Fig. 3a in Caza et al.[^▪▪].

FIGURE 2

Distribution of podocyte antigens in ‘primary’ (left) and malignancy-associated (right) membranous nephropathy. The piechart on the left is an extrapolation from refs. [^▪▪,^▪▪,^▪▪,18]. Prevalences should be confirmed in future studies. The piechart on the right is adapted from Supplemental Fig. 6 in Caza et al.[^▪▪].