Membranous nephropathy is a common cause of a nephrotic syndrome in adult patients and often leads to loss of renal function. A nephrotic syndrome is characterized by loss of large amounts of plasma proteins in the urine, edema, low plasma protein concentrations, and high plasma concentrations of lipids. The diagnosis is made by renal biopsy.

Membranous nephropathy is an autoimmune disease, meaning that the immune system is misled and attacks proteins that are present in the kidney. Our group was essentially involved in the characterization of two of the attacked proteins, PLA2R1 and THSD7A. A better understanding of these immune processes and mechanisms is the requirement for the development of more effective therapies for patients with membranous nephropathy.

Our research primarily targets the following questions:

• 1. Why and how is the immune system misled to attack the kidney?

• 2. Which molecular mechanisms mediate the damage of the renal filtration barrier?

• 3. Which experimental therapies could represent an alternative to the unspecific suppression of the immune system that is the therapeutical standard to date?

Thereby, we focus on clinical and animal studies with investigation of mouse models that we were able to characterize in the last years.

Nicola M. Tomas - Principal Investigator

Gunther Zahner - Principal Investigator

Larissa Seifert - PhD Student

Silke Dehde - BTA

Catherine Meyer-Schwesinger, Nicola M. Tomas, Silke Dehde, Larissa Seifert, Irm Hermans-Borgmeyer, Thorsten Wiech, Friedrich Koch-Nolte, Tobias B. Huber and Gunther Zahner: A novel mouse model of phospholipase A2 receptor 1-associated membranous nephropathy mimics podocyte injury in patients. Kidney International, Volume 97, Issue 5, Pages 817, 2020

Seifert, L, Hoxha, E, Eichhoff, AM, Zahner, G, Dehde, S, Reinhard, L, Koch-Nolte, F, Stahl, RAK, Tomas, NM: The Most N-Terminal Region of THSD7A Is the Predominant Target for Autoimmunity in THSD7A-Associated Membranous Nephropathy. J Am Soc Nephrol, epub ahead of print, 2018

Tomas NM, Meyer-Schwesinger C, von Spiegel H, Kotb AM, Zahner G, Hoxha E, Helmchen U, Endlich N, Koch-Nolte F, Stahl RAK: A Heterologous Model of Thrombospondin Type 1 Domain-Containing 7A-Associated Membranous Nephropathy. J Am Soc Nephrol, epub ahead of print, 2017

Hoxha, E, Wiech, T, Stahl, PR, Zahner, G, Tomas, NM, Meyer-Schwesinger, C, Wenzel, U, Janneck, M, Steinmetz, OM, Panzer, U, Harendza, S, Stahl, RA: A Mechanism for Cancer-Associated Membranous Nephropathy. N Engl J Med, 374: 1995-1996, 2016

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: Autoantibodies against thrombospondin type 1 domain-containing 7A induce membranous nephropathy. J Clin Invest, 126: 2519-2532, 2016

Tomas, NM, Beck, LH, Jr., Meyer-Schwesinger, C, Seitz-Polski, B, Ma, H, Zahner, G, Dolla, G, Hoxha, E, Helmchen, U, Dabert-Gay, AS, Debayle, D, Merchant, M, Klein, J, Salant, DJ, Stahl, RA, Lambeau, G: Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med, 371: 2277-2287, 2014