| Autor: |
Anne-Laure Leblond, Birgit Helmchen, Maliki Ankavay, Daniela Lenggenhager, Jasna Jetzer, Fritjof Helmchen, Hueseyin Yurtsever, Rossella Parrotta, Marc E. Healy, Amiskwia Pöschel, Enni Markkanen, Nasser Semmo, Martin Ferrié, Laurence Cocquerel, Harald Seeger, Helmut Hopfer, Beat Müllhaupt, Jérôme Gouttenoire, Darius Moradpour, Ariana Gaspert, Achim Weber |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-12 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-53072-0 |
| Popis: |
Abstract Hepatitis E virus (HEV) infection, one of the most common forms of hepatitis worldwide, is often associated with extrahepatic, particularly renal, manifestations. However, the underlying mechanisms are incompletely understood. Here, we report the development of a de novo immune complex-mediated glomerulonephritis (GN) in a kidney transplant recipient with chronic hepatitis E. Applying immunostaining, electron microscopy, and mass spectrometry after laser-capture microdissection, we show that GN develops in parallel with increasing glomerular deposition of a non-infectious, genome-free and non-glycosylated HEV open reading frame 2 (ORF2) capsid protein. No productive HEV infection of kidney cells is detected. Patients with acute hepatitis E display similar but less pronounced deposits. Our results establish a link between the production of HEV ORF2 protein and the development of hepatitis E-associated GN in the immunocompromised state. The formation of glomerular IgG-HEV ORF2 immune complexes discovered here provides a potential mechanistic explanation of how the hepatotropic HEV can cause variable renal manifestations. These findings directly provide a tool for etiology-based diagnosis of hepatitis E-associated GN as a distinct entity and suggest therapeutic implications. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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