Academic Journal
Pathogenicity of Human anti-PLA2R1 Antibodies in Minipigs:A Pilot Study
| العنوان: | Pathogenicity of Human anti-PLA2R1 Antibodies in Minipigs:A Pilot Study |
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| المؤلفون: | Reinhard, Linda, Wiech, Thorsten, Reitmeier, Aline, Lassé, Moritz, Machalitza, Maya, Heumann, Asmus, Ferru, Nicoletta, Loreth, Desiree, Schröder, Marie-Luise, Hutzfeldt, Arvid, Stahl, Felix R, Peine, Sven, Gröne, Hermann-Josef, Meyer-Schwesinger, Catherine, Rinschen, Markus M, Stahl, Rolf A K, Hoxha, Elion |
| المصدر: | Reinhard , L , Wiech , T , Reitmeier , A , Lassé , M , Machalitza , M , Heumann , A , Ferru , N , Loreth , D , Schröder , M-L , Hutzfeldt , A , Stahl , F R , Peine , S , Gröne , H-J , Meyer-Schwesinger , C , Rinschen , M M , Stahl , R A K & Hoxha , E 2023 , ' Pathogenicity of Human anti-PLA2R1 Antibodies in Minipigs : A Pilot Study ' , Journal of the American Society of Nephrology : JASN , vol. 34 .... |
| سنة النشر: | 2023 |
| المجموعة: | Aarhus University: Research |
| مصطلحات موضوعية: | Animals, Autoantibodies, Autoimmune Diseases, Glomerulonephritis, Membranous, Humans, Pilot Projects, Proteinuria, Proteomics, Receptors, Phospholipase A2, Swine, Miniature/metabolism, Virulence |
| الوصف: | BACKGROUND: Primary membranous nephropathy (MN) is an autoimmune kidney disease in which immune complexes are deposited beneath the epithelium in the glomeruli. The condition introduces a high risk for end-stage kidney disease. Seventy to 80 percent of patients with MN have circulating antibodies against phospholipase A2 receptor 1 (PLA2R1), and levels correlate with treatment response and prognosis. However, experimental evidence that human anti-PLA2R1 antibodies induce MN has been elusive. METHODS: In passive transfer experiments, minipigs received plasma or purified IgG from patients with PLA2R1-associated MN or from healthy controls. Anti-PLA2R1 antibodies and proteinuria were monitored using Western blot, ELISA, and Coomassie staining. Kidney tissues were analyzed using immunohistochemistry, immunofluorescence, electron microscopy, and proteomic analyses. RESULTS: Minipigs, like humans, express PLA2R1 on podocytes. Human anti-PLA2R1 antibodies bound to minipig PLA2R1 in vitro and in vivo. Passive transfer of human anti-PLA2R1 antibodies from patients with PLA2R1-associated MN to minipigs led to histological characteristics of human early-stage MN, activation of components of the complement cascade, and low levels of proteinuria. We observed development of an autologous, later phase of disease. CONCLUSIONS: A translational approach from humans to minipigs showed that human anti-PLA2R1 antibodies are pathogenic in MN, although in the heterologous phase of disease only low-level proteinuria developed. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1681/ASN.0000000000000068 |
| الاتاحة: | https://pure.au.dk/portal/en/publications/5f7b4d81-644a-4be6-a64f-b078fad0ebb4 https://doi.org/10.1681/ASN.0000000000000068 http://www.scopus.com/inward/record.url?scp=85149168465&partnerID=8YFLogxK |
| Rights: | info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.D0A6F3D3 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1681/ASN.0000000000000068 |
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