A HEV ORF2 protein-mediated mechanism of hepatitis E-associated kidney disease

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 developed 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. The formation of glomerular IgG-HEV ORF2 immune complexes discovered here provides a mechanistic explanation of how the actually 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.

INSTRUMENT(S): timsTOF Pro, Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Liver, Kidney

DISEASE(S): Hepatitis E

SUBMITTER: Anne-Laure Leblond  

LAB HEAD: Prof. Dr.

PROVIDER: PXD055348 | Pride | 2025-01-18

REPOSITORIES: pride