Update on New Antigens in the Pathogenesis of Membranous Nephropathy

Abstract

Previously, membranous nephropathies were divided into primary and secondary categories when the exact mechanism or pathogenetic factor were unknown. Approximately 70% accounted for primary membranous nephropathies. The remaining 30% were called secondary because they developed due to well-known diseases such as autoimmune diseases, tumours, infections, or drug assumptions. The discoveries of the M-type phospholipase A2 receptor and of thrombospondin type 1 domain containing 7A as causative antigens in a part of the so-called primary membranous nephropathies opened new knowledge on the effective causes of a large part of these diseases. The availability of novel techniques such as laser micro-dissection and tandem mass spectrometry, as well as immunochemistry with antibodies directed against novel proteins, allowed the confirmation of new antigens involved. The use of confocal microscopy and Western blot allowed detection of the new antigen on glomerular membrane, and the same antigen and relative antibodies have been detected in serum samples. Through these techniques, four new antigens were first detected, including neural epidermal growth factor 1 and semaphorin 3B in the so-called primary membranous nephropathy, and exostosin 1 and 2 and neural cell adhesion molecule 1 in lupus membranous nephropathy. The aim of this study is to describe the characteristics of the new antigens discovered and their association with other diseases. In addition, new antigens are on the horizon, and the story of primary membranous nephropathy is still to be completely written and understood.