• Stahl Rolf A K RAK Zentrum für Innere Medizin, lll. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Deutschland. rstahl@uke.d and Elion Hoxha.
• Zentrum für Innere Medizin, lll. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Deutschland. rstahl@uke.de.
• Internist (Berl). 2019 May 1; 60 (5): 440-449.

BackgroundMembranous glomerulonephritis (MGN) is the most frequent cause of a nephrotic syndrome in adults. It is an autoimmune disease caused by binding of autoantibodies to endogenous proteins expressed on glomerular podocytes. Antibody binding and activation of inflammatory mediators result in the onset of proteinuria. Recently, two endogenous podocytic target antigens in MGN have been characterized and their clinical role is a main focus of research in nephrology.ObjectiveThe discovery that antibodies against phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type 1 domain containing 7A (THSD7A) mediate the pathogenesis of MGN leads to the question of what clinical role these antibodies have in patients with MGN.Material And MethodsEvidence published in recent years on the role of the described antigens is analyzed and critically discussed. The clinical conclusions derived for patients with MGN are presented.ResultsAntibodies against PLA2R1 are detectable in approximately 80% of patients with MGN, while 2-3% of patients have antibodies against THSD7A. Serum analyses of antibodies and immunohistological staining in kidney biopsies enable an almost 100% certain diagnosis of PLA2R1 and THSD7A-mediated MGN. Serum levels of PLA2R1 antibodies are predictors for the response to therapy, determine the prognosis and allow an exact individualized monitoring of treatment. The THSD7A antibodies are associated with an increased prevalence of malignant tumors and play a pathogenetic role in the genesis of this secondary form of MGN.ConclusionThe characterization of the antibodies responsible for the development of MGN is an example of precision medicine in nephrology and the foundation for the development of new, curative treatments.

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