SFB 1192

Project B6

Role of Role of factor H related (FHR) proteins in glomerular diseases

Sequence- and copy number variations in the human Factor H-CFHR gene cluster are linked to the kidney diseases, atypical Hemolytic Uremic Syndrome, C3 Glomerulopathy, Membranous Nephropathy, IgA Nephropathy and Systemic Lupus Erythematosus. Deletions or duplications generate mutant CFHR-genes resulting in the expression of FHR::FHR- and FHR::Factor H-hybrid-proteins and an altered FHR-, Factor H, plasma repertoire. This disease association shows an essential role of FHR proteins for glomerular integrity. FHRs are emerging complement and immune modulators: FHR1 is an inflammatory mediator and controls Factor H surface action whereas FHR2 blocks C3 convertase action and inhibits FHR1 mediated inflammation. FHR5 is a complement activator. FHRs together with Factor H, the central C3 convertase regulator, adjust complement activity in glomeruli. A clear association is emerging between genetic modifications and the various pathologic outcomes.

We aim to define how altered FHR variants cause pathology in the kidney, and evaluate whether FHR deposition in renal biopsies serve as diagnostic and predictive markers. We are interested to define role of FHR2 and FHR5 and evaluate how new FHR2 variants (not listed in the exome aggregation consortium database, ExAc) influence complement action, affect surface binding and complement regulation. Furthermore correlate FHR1-, FHR2- and FHR5 deposition with morphological changes, immunohistological staining or cellular modifications to define unique patterns for the various glomerular diseases, and aim to develop FHRs as diagnostic markers and coordinate with clinicians for individualized, complement targeting therapy.


  • Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies

    Sarah Irmscher, Silke R. Brix, Svante L. H. Zipfel, Luke D. Halder, Sibel Mutlutürk, Sonia Wulf, Evaldas Girdauskas, Hermann Reichenspurner, Rolf A. K. Stahl, Berit Jungnickel, Thorsten Wiech, Peter F. Zipfel & Christine SkerkaNat Commun. 2019 Jul

  • C3-Glomerulopathy Autoantibodies Mediate Distinct Effects on Complement C3- and C5-Convertases.

    Zhao F, Afonso S, Lindner S, Hartmann A, Löschmann I, Nilsson B, Ekdahl KN, Weber LT, Habbig S, Schalk G, Kirschfink M, Zipfel PF, Skerka C.Front Immunol. 2019 May

  • C3 Glomerulopathy-Understanding a Rare Complement-Driven Renal Disease.

    Smith RJH, Appel G, Blom AM, Cook HT, D’Agati V, Fakhouri F, Véronique Fremeaux-Bacchi V, Józsi M, Kavanagh D, Lambris J, Noris M, Pickering MC, Remuzzi G, Santiago Rodriguez de Córdoba S, Sethi S, Van der Vlag J, Zipfel PF, Nester CMNat Rev Nephrol. 2019 Mar

  • Bevacizumab-associated glomerular microangiopathy.

    Person F, Rinschen M, Brix S, Wulf S, Noriega M, Fehrle W, Schmitz J, Schwarz A, Ivanyi P, Steinmetz O, Reinhard L, Hoxha E, Zipfel P, Bräsen J, Wiech TMod Pathol. 2018 Dec

  • Development and validation of a renal risk score in ANCA-associated glomerulonephritis

    Brix S, Noriega M, Tennstedt P, Vettorazzi E, Busch M, Nitschke M, Jabs W, Özcan F, Wendt R, Hausberg M, Sellin L, Panzer U, Huber T, Waldherr R, Hopfer H, Stahl R, Wiech TKidney Int. 2018 Dec

  • Potential role for urine PCR in the diagnosis of Whipple's disease.

    Moter A, Janneck M, Wolters M, Iking-Konert C, Wiessner A, Loddenkemper C, Hartleben B, Lütgehetmann M, Schmidt J, Langbehn U, Janssen S, Geelhaar-Karsch A, Schneider T, Moos V, Rohde H, Kikhney J, Wiech T.Clin Infect Dis. 2018 Oct

  • Lupusnephritis

    Melderis S, Wiech T, Iking-Konert C, Steinmetz OZ Rheumatol. 2018 Sep

  • Organisation of lymphocytic infiltrates in ANCA-associated glomerulonephritis

    Brix S, Noriega M, Herden E, Goldmann B, Langbehn U, Busch M, Jabs W, Steinmetz O, Panzer U, Huber T, Stahl R, Wiech THistopathology. 2018 Jun

  • FHR5 Binds to Laminins, Uses Separate C3b and Surface-Binding Sites, and Activates Complement on Malondialdehyde-Acetaldehyde Surfaces.

    Rudnick RB, Chen Q, Stea ED, Hartmann A, Papac-Milicevic N, Person F, Wiesener M, Binder CJ, Wiech T, Skerka C, Zipfel PFJ Immunol. 2018 Apr

  • FHR3 Blocks C3d-Mediated Coactivation of Human B Cells. 

    Buhlmann D, Eberhardt HU, Medyukhina A, Prodinger WM, Figge MT, Zipfel PF, Skerka CJ Immunol. 2016 Jul

III. Medizinische Klinik und Poliklinik
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