SFB 1192

Project B1

Membranous Nephropathy: The clinical role of pathogenetic mechanisms

The discovery of the phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type-1 domain-containing 7A (THSD7A) as target antigens in membranous nephropathy (MN) has led to a major progress in the understanding of the pathophysiology of the disease. The immunologic targets in the kidneys can now be investigated in more detail, while antibody levels serve as clinical markers allowing a better differential diagnosis and helping to assess treatment response and prognosis of patients with MN.

Now for almost 80% of patients with MN a pathogenesis-related diagnosis can be made. However, in the remaining 20% of patients the pathomechanisms of disease remain unclear and their clinical course is unpredictable. Thus, their pathophysiology should be better defined.

Figure 1: PLA2R1 and THSD7A staining of human kidney tissue. Both antigens are detectable on human podocytes.

Even though PLA2R1 and THSD7A are now characterized antigens in primary MN, it is still unclear, why they serve as targets of the immune system and which roles the molecules have in the disease onset and the glomerular pathobiology. Furthermore, it is still not defined which role the IgG4 subtype plays in the activation of the complement system, which plays a dominant role in the mediation of MN. Therefore, the identification of additional target antigens in PLA2R1 and THSD7A antibody negative patients, the characterization of the pathogenetic role of these known antigens and the mechanisms, how complement is activated are the aims of this project. It is the long-term objective to characterize for each patient with MN its molecular pathogenesis in order to develop a tailored treatment strategy to make end-stage renal disease in these patients a history.

Publications

  • Role of phospholipase A2 receptor 1 antibody level at diagnosis for long-term renal outcome in membranous nephropathy.

    Mahmud M, Pinnschmidt HO, Reinhard L, Harendza S, Wiech T, Stahl RAK, Hoxha E PLoS One. 2019 Sep

  • Diagnostic role of renal biopsy in PLA2R1-antibody-positive patients with nephrotic syndrome.

    Wiech T, Stahl RAK, Hoxha E Mod Pathol. 2019 Sep

  • 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

  • Antigen-Specific IgG Subclasses in Primary and Malignancy-Associated Membranous Nephropathy.

    von Haxthausen F, Reinhard L, Pinnschmidt HO, Rink M, Soave A, Hoxha E, Stahl RAKFront Immunol. 2018 Dec

  • Characterization of Autoantibodies in Primary Membranous Nephropathy and their clinical Significance.

    Stahl RAK, Reinhard L, Hoxha E.Expert Rev Clin Immunol. 2018 Nov

  • Genetics of membranous nephropathy.

    Gupta S, Köttgen A, Hoxha E, Brenchley P, Bockenhauer D, Stanescu HC, Kleta R.Nephrol Dial Transplant. 2018 Sep

  • The Most N-Terminal Region of THSD7A Is the Predominant Target for Autoimmunity in THSD7A-Associated Membranous Nephropathy.

    Seifert L, Hoxha E, Eichhoff AM, Zahner G, Dehde S, Reinhard L, Koch-Nolte F, Stahl RAK, Tomas NMJ Am Soc Nephrol. 2018 May

  • Immunohistochemical and serological characterization of membranous nephropathy in children and adolescents

    Dettmar A, Wiech T, Kemper M, Soave A, Rink M, Oh J, Stahl R, Hoxha E Pediatr Nephrol. 2018 Mar

  • A Heterologous Model of Thrombospondin Type 1 Domain-Containing 7A-Associated Membranous Nephropathy

    Tomas N, Meyer-Schwesinger C, von Spiegel H, Kotb A, Zahner G, Hoxha E, Helmchen U, Endlich N, Koch-Nolte F, Stahl R J Am Soc Nephrol. 2017 Nov

  • Translational Aspects of Primary Membranous Nephropathy.

    Hoxha E, Stahl RAK.Semin Nephrol. 2017 Sep

  • Membranous nephropathy-one morphologic pattern with different diseases

    Hoxha E, von Haxthausen F, Wiech T, Stahl RPflugers Arch. 2017 Aug

  • THSD7A expression in human cancer

    Stahl P, Hoxha E, Wiech T, Schröder C, Simon R, Stahl R Genes Chromosomes Cancer. 2017 Apr

  • An Indirect Immunofluorescence Method Facilitates Detection of Thrombospondin Type 1 Domain-Containing 7A-Specific Antibodies in Membranous Nephropathy

    Hoxha E, Beck L, Wiech T, Tomas N, Probst C, Mindorf S, Meyer-Schwesinger C, Zahner G, Stahl P, Schöpper R, Panzer U, Harendza S, Helmchen U, Salant D, Stahl R J Am Soc Nephrol. 2017 Feb

  • Autoantibodies against thrombospondin type 1 domain-containing 7A induce membranous nephropathy. 

    Tomas NM, Hoxha E, Reinicke AT, Fester L, Helmchen U, Gerth J, Bachmann F, Budde K, Koch-Nolte F, Zahner G, Rune G, Lambeau G, Meyer-Schwesinger C, Stahl RA.J Clin Invest. 2016 Jul

  • A Mechanism for Cancer-Associated Membranous Nephropathy. 

    Hoxha E, Wiech T, Stahl PR, Zahner G, Tomas NM, Meyer-Schwesinger C, Wenzel U, Janneck M, Steinmetz OM, Panzer U, Harendza S, Stahl RAN Engl J Med. 2016 May

III. Medizinische Klinik und Poliklinik
Universitätsklinikum Hamburg-Eppendorf

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20246 Hamburg, Germany
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