Pathophysiologic and Antigene-specific Therapeutic Approaches of the Phospholipase A2 Receptor-mediated Membranous Nephropathy

• Applicant: Privatdozent Dr. Gunther Zahner
• Subject Area: Nephrology ; Immunology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 451019656

In adults membranous nephropathy (MN) is the most common cause of nephrotic syndrome worldwide. Within ten years about 30 % of the patients suffering from primary MN develop end stage renal disease. In 2009 phospholipase A2 receptor-1 (PLA2R1), the first MN-specific antigen that is responsible for 70 to 80 % of the primary MN cases in humans, was discovered. Due to the lack of an endogenous PLA2R1 expression in rodents, the pathogenicity of anti-PLA2R1 antibodies was described 10 years later by our group.That means, PLA2R1-specific transgenic mouse-models are exclusively available now for these studies. Via these new models we want 1. to characterize the PLA2R1-associated experimental autoimmune model, 2. to study the role of the complement-system as well as the interactome and 3. to deplete the PLA2R1-specific autoantibodies and B-cells respectively. Thus, using our new PLA2R1-specific mouse-models, the unique opportunity exists to examine the behavior of "membranous podocytes" in different stages of PLA2R1-mediated experimental MN as well as to develop antigen-specific therapeutic options.

• DFG Programme: Research Grants