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HEV ORF2 protein-antibody complex deposits are associated with glomerulonephritis in hepatitis E with reduced immune status.

Authors :
Leblond, Anne-Laure
Helmchen, Birgit
Ankavay, Maliki
Lenggenhager, Daniela
Jetzer, Jasna
Helmchen, Fritjof
Yurtsever, Hueseyin
Parrotta, Rossella
Healy, Marc E.
Pöschel, Amiskwia
Markkanen, Enni
Semmo, Nasser
Ferrié, Martin
Cocquerel, Laurence
Seeger, Harald
Hopfer, Helmut
Müllhaupt, Beat
Gouttenoire, Jérôme
Moradpour, Darius
Gaspert, Ariana
Source :
Nature Communications; 10/17/2024, Vol. 15 Issue 1, p1-12, 12p
Publication Year :
2024

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. It's poorly understood how renal manifestations develop in HEV infection in patients. Here, the authors observe glomerular accumulation of the viral protein ORF2 in complex with host IgG in immunocompromised patients with chronic or acute HEV infection who developed glomerulonephritis. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20411723
Volume :
15
Issue :
1
Database :
Complementary Index
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
180369956
Full Text :
https://doi.org/10.1038/s41467-024-53072-0