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.

A Review of Therapy for Primary Membranous Nephropathy Post-MENTOR

“…Primary membranous nephropathy (PMN) is the most common cause of nephrotic syndrome in adults, accounting for 20-40% of all cases. It is an autoimmune disease with an incidence rate of 1.2 per 100,000 persons per year, and a male to female ratio of 2:1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. The discovery of autoantibodies to phospholipase A2 receptor (PLA2R) by Beck and Salant in 2009 revolutionized our understanding of the pathophysiology of this unique disease [2].…”

“…PLA2R, a normal molecule in the podocyte structure, serves as the target antigen for PLA2R antibodies, causing an immunological response that results in the clinical signs of proteinuria and hypoalbuminemia [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Furthermore, the identification of this antigen and antibody has had a significant impact on the treatment approach.…”

“…Furthermore, the identification of this antigen and antibody has had a significant impact on the treatment approach. A serological approach involving evaluation of the PLA2R antibody levels has been proposed, which serve not only as a marker of disease evolution, but also as a determining factor for treatment [11,12].…”

“…The purpose of this review is to illustrate the changing landscape of PMN therapy post-MEN-TOR, highlighting alternative therapies including rituximab and other agents that have been used more recently instead of the tried and tested cyclical regimen consisting of corticosteroids, alkylating agents, and calcineurin inhibitors. Alkylating agents and calcineurin inhibitors have significant adverse effects, including gonadal toxicity, bone marrow suppression, oncogenic effects, and nephrotoxicity [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16].…”

“…This therapeutic approach is effective as remission rates reportedly vary from 77% to 93% [6]. Of concern is that these agents are associated with an adverse risk profile that includes malignancy, gonadal toxicity, infection, dermatological manifestations, and bone marrow suppression, thus requiring caution in their use [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16].…”