Role of Complement Factor H Related Gene 2 in C3 Glomerulopathy

C3 glomerulopathy is a new name for a group of glomerular pathologies associated with dominant glomerular complement C3 deposition as a marker of local complement action. The disease subforms exhibit different morphologic patterns in light- and electron microscopy and are often associated with defective regulation of the alternative complement pathway in fluid phase. Some C3 glomerulopathy patients have mutations in genes coding for the complement regulator Factor H and for C3, the central complement component. In addition patients with acquired forms develop autoantibodies, such as C3 nephritic factor, as well as autoantibodies reacting with the C3 convertase, with Factor H or with Factor B. Recent work shows that mutations and copy number variations in the complement factor H related gene 2 (CFHR2) are associated with C3 glomerulopathy. However, the exact role of the CFHR2 protein as complement regulator or modulator, as well as the exact mechanism how CFHR2 hybrid proteins resulting from copy number variations in the CFHR gene cluster cause glomerular pathology are unclear. In this project we aim to define the role of CFHR2 in C3G pathophysiology and to combine the Hamburg Glomerulonephrits and the Jena MPGN/C3G registries in order to identify if CFHR2 associated C3 glomerulopathy represents a unique subform of this kidney disease. Such a detailed understanding of the central disease principles is expected to allow pathogenesis based response prediction of complement targeting therapy.

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