KFO 228: Immunopathogenesis and Therapy of Glomerulonephritis
Final Report Abstract
Glomerulonephritis as a disease category is one of the leading causes of end-stage renal disease in the Western world and is associated with significant morbidity and mortality. Glomerulonephritis represents a heterogeneous collection of disease entities. However, fundamental to each form of glomerulonephritis is the immune-mediated renal damage which consists of a specific immune reaction followed by an effector phase of inflammation. This pathophysiological concept is the current rationale for unspecific immunosuppressive therapy with corticosteroids and cytotoxic agents. The missing specificity of these therapeutic regimes, however, and their frequently disabling side effects are the main reasons for the urgent need to develop new and more specific individual therapeutic strategies. Our Clinical Research Unit (KFO 228) combined clinicians and basic scientists with a strong expertise in human and experimental glomerulonephritis, in cellular immunology and in renal pathology. The KFO 228 improved the understanding of several aspects of the immunopathogenesis of human and experimental glomerulonephritis using state-of-the-art techniques and (transgenic) animal models, combined with clinical studies in a new established large cohort of patients with glomerulonephritis (“Hamburg GN-Registry”). One of the main research achievements was in depth characterization of the pathogenic Th17 axis in murine models of crescentic and proliferative GN. Subsequent analysis revealed a high frequency of Th17 cell in the kidney of ANCA-glomerulonephritis patients, which is a prerequisite for translating the findings gained from animal models into clinical practice in the future. Moreover, we established assays for the detection and quantification of phospholipase A2 receptor (PLA2R) antibody serum levels of patients with Membranous Nephropathy and demonstrated that PLA2R antibody levels are associated with clinical activity of the disease. Moreover, the Clinical Research Unit was instrumental for the identification of THSD7A as an additional target antigen in Membranous Nephropathy and for the subsequent demonstration of the pathogenic and diagnostic role of this autoantibody in Membranous Nephropathy. Taken together the KFO 228 supported the identification of novel diagnostic, prognostic and therapeutic strategies for autoimmune kidney diseases. In addition, the Clinical Research Unit provided the structural and topical background for the currently established Collaborative Research Center (SFB 1192) “Immune-Mediated Glomerular Diseases” in Hamburg.
