Antigen-specific therapies of membranous nephropathy

Abstract

Membranous nephropathy (MN) is a rare but potentially severe kidney disease and a major cause of nephrotic syndrome in adults. It is defined by immune deposits at the glomerular basement membrane and destruction of the podocyte. Immune deposits are formed through autoantibodies targeting antigens on the podocyte surface such as PLA2R and THSD7A and subsequent binding of complement factors. The resulting proteinuria can result in hyperlipidemia, hypoalbuminemia and ultimately kidney failure. So far, patients have been treated with drugs that generally suppress the immune system leaving patients susceptible to secondary infections. In an effort to create antigen-specific therapies that target pathogenic autoantibodies exclusively, antibody Fc fusion constructs (AgFcs) were generated. Overall, the preclinical experiments demonstrate in this thesis show the potential of AgFcs to efficiently decrease antibody levels in an antigen-specific way, which could represent a highly specific, less toxic treatment for MN and other antibody-mediated autoimmune diseases in the future.