Primary Membranous Nephropathy as a Model of Autoimmune Disease

Membranous nephropathy is the most common cause of adult nephrotic syndrome worldwide with a significant health care burden. There has been a leap in our understanding of the disease mechanism over the last decade with a remarkably strong genetic component to the development of the disease and its strong association with high affinity antibody—in the form of anti-PLA2R autoantibody in the majority of cases, with a smaller proportion associated with anti-THSD7A autoantibody. New evidence is now providing confirmation of specific elements in the development of the disease pathogenesis, such as involvement of loss of peripheral tolerance. There is a striking correlation between disease activity and anti-PLA2R antibody levels, along with response to treatment; evidence points strongly to these antibodies being pathogenic. The development of membranous nephropathy therefore follows the well appreciated multi-hit step-wise path to autoimmune clinical disease. Given its strong genetic basis and putative pathogenic antibody the disease provides an invaluable model for understanding of autoimmunity. This chapter focuses on the most up to date knowledge of autoimmune membranous nephropathy and provides a paradigm for understanding the underlying disease mechanisms in autoimmunity.