Membranous Nephropathy: Antigenic Landscape and a Novel Pathogenetic Model

Membranous nephropathy is a disease that has been well documented, yet its etiopathogenesis has not been fully clarified and the distinction between its primary and secondary forms has not been completely categorized. The discovery of new antigens and antibodies reveals different percentages of positivity in secondary membranous nephropathy, which is a cause of great confusion and ambiguity not only in diagnosis but also in the choice of a therapeutic approach. The aim of this review is to summarize the literature on newly discovered antigens and antibodies, and to propose a pathogenetic model based on the role of the complement system and its activation pathways. In this model, antigens are categorized based on the type of immunoglobulin deposits and the putative complement pathways that they activate, which can help to differentiate primary from secondary membranous nephropathy. The model also reflects how the deposition of foreign antigens in the basement membrane can activate both the lectin and classical complement pathways, which may explain why positive antibodies are observed in both primary and secondary forms of membranous nephropathy.