New antigens involved in membranous nephropathy beyond phospholipase A2 receptor

Abstract

When the physiopathology of membranous nephropathy was first described, almost 30% of cases were recognized to be secondary to well-known diseases such as autoimmune diseases, tumors or infections. The remaining 70% cases were called primary membranous nephropathy as the exact mechanism or pathogenic factor involved was unknown. The discovery of the M type phospholipase A2 receptor and thrombospondin type 1 domain containing 7A as causative antigens in these “so called” primary membranous nephropathies provided new insights into the effective causes of a large proportion of these cases. Novel techniques such as laser microdissection and tandem mass spectrometry as well as immunochemistry with antibodies directed against novel proteins allowed the confirmation of new involved antigens. Finally, using confocal microscopy to localize these new antigens and immunoglobulin G and Western blot analysis of serum samples, these new antigens were detected on the glomerular membrane, and the related antibodies were detected in serum samples. The same antigens have been recognized in some cases of secondary membranous disease due to autoimmune diseases, tumors and infections. This has allowed examination of the relationship between antigens in primary membranous nephropathy and their presence in some secondary nephropathies. The aim of this study is to describe the characteristics of the new antigens discovered and their association with other diseases.

Keywords: Membranous nephropathy, Exostosin ½, Neural cell adhesion molecule 1, Neural epidermal growth factor like-1 protein, Protocadherin 7, Semaphorin 3B

Core Tip: The pathophysiological mechanisms of membranous nephropathy have been partially known for a long time. Novel techniques have allowed identifying several antigens and the corresponding antibodies as the main cause of a large part of these diseases. Therefore, a large part of membranous nephropathy, once called primary, are due to immune complexes whose components are now recognized. The same antigens have been recognized in a part of secondary membranous disease, which are due to autoimmune diseases, tumors and infections, diseases. This fact allows a relationship between antigens found either in primary membranous nephropathy or in some forms of secondary nephropathies.