Membranous Nephropathy (MN) is one of the most common causes for a nephrotic syndrome in adults and leads in up to 40% of cases to end-stage renal disease. MN is an autoimmune disease, caused by binding of circulating antibodies to endogenous or planted exogenous antigens. In up to 20% of cases MN is associated with other diseases, most notably malignancies, infections and autoimmune diseases.

In 75-80% of cases the podocytic target antigen in MN is Phospholipase A2 Receptor 1 (PLA2R1). Thrombospondin Type 1 Domain Containing 7A (THSD7A) is a second target antigen, causing MN in 2-3% of patients. Autoantibody levels in patients with MN are closely associated with treatment response and prognosis. Moreover, THSD7A-associated MN is often associated with malignancies.

The main focus of our group is the study of pathomechanisms of membranous nephropathy (MN) using translational approaches. Some of our major contributions in the field of MN have been the characterization of the clinical role of domain-specific PLA2R1-antibodies and of THSD7A-antibodies for the diagnosis, management and prognosis estimation of MN; the characterization of the pathogenicity of the PLA2R1-antibody in MN; the identification of Netrin G1 as a new target antigen in MN; the identification of the potential molecular link between THSD7A-associated MN and malignancy. Our group has also established the Hamburg Glomerulonephritis Registry, one of the largest prospectively studied cohort of patients with glomerulonephritis worldwide. Our aim is to clarify the specific pathomechanisms leading to development and progression of human MN and translate the understanding of MN pathophysiology to novel, specific treatment options for patients with this disease.

Some of our major goals are:

the identification of new target antigens, leading to development of MN in patients who are negative for PLA2R1 and THSD7A antibodies; the investigation of the mechanisms leading to development of autoimmunity and production of PLA2R1 and THSD7A antibodies in patients with MN; the characterization of pathomechanisms involved in disease progression, including characterization of pathogenic epitopes on the target antigens, antibody subclasses and complement activation. Our main objective is the development of new treatment strategies for patients with MN, which are individualized, specific, non-immunosuppressive and therefore less toxic.