{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:13:13Z","timestamp":1793059993722,"version":"4.5.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"S1","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/deed.de"},{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/deed.de"}],"funder":[{"DOI":"10.13039\/501100006447","name":"University of Zurich","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006447","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pathologie"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and objective<\/jats:title>\n                    <jats:p>Hepatitis\u00a0E virus (HEV) infection, one of the most common forms of hepatitis worldwide, is often associated with extrahepatic manifestations, particularly renal disease. While the underlying pathomechanisms are still largely unknown, these manifestations are thought to develop either directly, i.e., by HEV infection of the respective organ, or indirectly, i.e., via immunologic reactions. Herein, we describe the development of de novo immune complex-mediated glomerulonephritis (GN) associated with the glomerular deposition of a\u00a0newly described form of the HEV open reading frame\u00a02 (ORF2) capsid protein in patients with chronic or acute hepatitis\u00a0E.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed immunostaining, electron and deconvolution microscopy, and laser-capture microdissection combined with mass spectrometry to specifically investigate the glomerular compartment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In a\u00a0kidney transplant recipient with chronic hepatitis\u00a0E, we show that GN developed in parallel with increasing glomerular deposits of the HEV ORF2 protein, which significantly colocalizes with IgG, thus forming immune complexes. Interestingly, the glomerular HEV ORF2 protein does not correspond to the expected secreted and glycosylated form of the viral capsid protein but rather has the molecular weight of a\u00a0truncated non-glycosylated form. Importantly, it is not associated with HEV RNA and, in contrast to the situation in liver cells, no productive HEV infection of kidney cells is detected. Patients with acute hepatitis\u00a0E show similar but less pronounced deposits. Our results establish a\u00a0link between the production of HEV ORF2 protein and the development of hepatitis\u00a0E-associated GN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The formation of glomerular IgG\u2013HEV ORF2 immune complexes discovered here provides a\u00a0mechanistic explanation of how the hepatotropic HEV can cause variable renal manifestations. These findings directly provide a\u00a0tool for etiology-based diagnosis of hepatitis\u00a0E-associated GN, establish hepatitis\u00a0E-associated GN as a\u00a0distinct entity, and suggest therapeutic implications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00292-025-01499-7","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T14:25:57Z","timestamp":1763994357000},"page":"27-31","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unraveling a\u00a0mechanism underlying hepatitis\u00a0E-associated kidney disease","Entr\u00e4tseln eines der Hepatitis-E-assoziierten Nierenerkrankung zugrunde liegenden Mechanismus"],"prefix":"10.1007","volume":"47","author":[{"given":"Anne Laure","family":"Leblond","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"1499_CR1","unstructured":"WHO Hepatitis\u00a0E. 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J\u00a0Hepatol 67:471\u2013479","journal-title":"J Hepatol"}],"container-title":["Die Pathologie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00292-025-01499-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00292-025-01499-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00292-025-01499-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T09:57:20Z","timestamp":1768816640000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00292-025-01499-7"}},"subtitle":["Discovery of HEV ORF2 capsid protein-associated immune complex glomerulonephritis","Entdeckung der HEV-ORF2-Kapsid-Protein-assoziierten Immunkomplexglomerulonephritis"],"short-title":[],"issued":{"date-parts":[[2025,11,24]]},"references-count":27,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["1499"],"URL":"https:\/\/doi.org\/10.1007\/s00292-025-01499-7","relation":{},"ISSN":["2731-7188","2731-7196"],"issn-type":[{"value":"2731-7188","type":"print"},{"value":"2731-7196","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,24]]},"assertion":[{"value":"16 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"A.L.\u00a0Leblond declare that she has no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Written informed consent (provided by Springer Nature) was given by the next of kin of all patients according to CARE guidelines and in compliance with the principles of the Declaration of Helsinki. Clinical data have been anonymized. Sex and gender were not taken into consideration. This study was approved by the internal review board of the University Hospital Zurich and the Cantonal Ethics Committee of Zurich, Switzerland (KEK-ZH-Nr. 2013-0504).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The supplement containing this article is not sponsored by industry.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}