Membranous nephropathy: Pathogenetic mechanisms and clinical implications
The identification of the phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type 1 domain containing 7A (THSD7A) as major target antigens in membranous nephropathy (MN) has fundamentally changed the scientific and clinical approach to this disease. The diagnosis of MN is now made based on the molecular pathogenesis of the disease. Treatment decisions and prediction of prognosis are based on the immune pathomechanisms of disease, allowing a more precise and individualized therapy. Currently, the basic treatment options for MN remain immunosuppressive and not specific for the disease itself. The development of novel treatment approaches, which are not based on a general immunosuppression, require a more profound understanding of the specific pathomechanisms leading to disease development and progression. To achieve this goal, we have the following aims in this project: 1) Identification of additional antigens in patients with MN, who are negative for PLA2R1 and THSD7A antibodies. For this purpose, we have developed new screening and antigen retrieval and detection strategies, which will allow us to detect susceptible antigens evading detection by conventional methods. 2) Characterization of B cell subsets and their role in the pathogenesis of human MN. This will allow a better prognosis of treatment success and potentially help to develop more specific treatment strategies. 3) A better understanding of the pathogenesis of PLA2R1 and THSD7A antibody mediated MN. To this end, we aim to implement an animal model for PLA2R1- associated MN in minipigs. This model will not only prove the pathogenicity of PLA2R1 antibodies, but will also be crucial for the implementation of novel treatment strategies in MN. These studies will be essential to further improve our understanding of the pathophysiology of MN, which is a prerequisite for the development of pathogenesis-based and personalized treatments.
Pathogenicity of Human Anti-PLA 2 R1 Antibodies in Minipigs: A Pilot Study.
Linda Reinhard, Thorsten Wiech, Aline Reitmeier, Moritz Lassé, Maya Machalitza, Asmus Heumann, Nicoletta Ferru, Desiree Loreth, Marie-Luise Schröder, Arvid Hutzfeldt, Felix R Stahl, Sven Peine, Hermann-Josef Gröne, Catherine Meyer-Schwesinger, Markus M Rinschen, Rolf A K Stahl, Elion HoxhaJ Am Soc Nephrol. 2023 Mar
False positivity for PLA2R1 antibody measured by ELISA in a nephrotic patient with no membranous nephropathy.
Elion Hoxha, Linda Reinhard, Thomas Castedello, Jan U BeckerKidney Int. 2023 Feb
Bacterial infection possibly causing autoimmunity: Tropheryma whipplei and membranous nephropathy.
Thorsten Wiech, Linda Reinhard, Sonia Wulf, Alfio Edoardo Giuffrida, Elisa Longhitano, Rosario Caruso, Hermann-Josef Gröne, Rolf A K Stahl, Peter F Zipfel, Judith Kikhney, Annette Moter, Elion Hoxha, Domenico SantoroLancet. 2022 Nov
Netrin G1 Is a Novel Target Antigen in Primary Membranous Nephropathy.
Linda Reinhard, Maya Machalitza, Thorsten Wiech, Hermann-Josef Gröne, Moritz Lassé, Markus M Rinschen, Nicoletta Ferru, Jan Hinrich Bräsen, Friederike Drömann, Peter Maria Rob, Sanjeev Sethi, Elion Hoxha, Rolf A K StahlJ Am Soc Nephrol. 2022 Oct
Membranous nephropathy: new pathogenic mechanisms and their clinical implications.
Elion Hoxha, Linda Reinhard, Rolf A K StahlNat Rev Nephrol. 2022 Apr
A New Chemiluminescence Immunoassay for Phospholipase A2 Receptor 1 Autoantibodies Allows Early Identification of Autoantibody Recurrence in Patients With Membranous Nephropathy.
Elion Hoxha, Rolf A K Stahl, Linda Reinhard, Alexander Kühnl, Wolfgang Schlumberger, Cornelia DähnrichKidney Int. Rep. 2021 Jan
Is primary membranous nephropathy a complement mediated disease?
Linda Reinhard, Rolf A K Stahl, Elion HoxhaMol Immunol. 2020 Dec
The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis.
Jingyuan Xie, Lili Liu, Nikol Mladkova, [...] Elion Hoxha, Rolf A K Stahl, [...] Robert Kleta, Nan Chen, Krzysztof KirylukNat Commun. 2020 Mar
Clinical Relevance of Domain-Specific Phospholipase A2 Receptor 1 Antibody Levels in Patients with Membranous Nephropathy.
Linda Reinhard, Gunther Zahner, Stephan Menzel, Friedrich Koch-Nolt, Rolf A K Stahl, Elion HoxhaJ Am Soc Nephrol. 2020 Jan
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
Prof. Dr. Rolf A. K. Stahl
PD Dr. Elion Hoxha
Dr. Linda Reinhard