{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T02:58:35Z","timestamp":1780714715065,"version":"3.54.1"},"reference-count":16,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T00:00:00Z","timestamp":1585872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatitis B virus (HBV) is a major cause of acute liver failure (ALF) worldwide. While liver damage in classic acute hepatitis B is believed to be T\u2010cell mediated, the pathogenesis of HBV\u2010associated ALF remains largely unknown. Access to liver specimens from well\u2010characterized patients with HBV\u2010associated ALF provided us with the opportunity to perform next\u2010generation sequencing (NGS) of the entire VH repertoires of IgM and IgG from the livers of four ALF patients, a control liver donor and a patient with chronic HBV infection. We found that ALF is not associated with expansion of specific B\u2010cell lineages. However, NGS showed that the intrahepatic VH repertoires from ALF patients were characterized by the abundant presence of antibodies in germline configuration in contrast to their marginal prevalence in controls. Moreover, NGS identified a large number of VH genes in germline configuration with identical VDJ sequences in the IgM and IgG repertoires in all four ALF patients, indicating that isotype switch from IgM to IgG had occurred without somatic hypermutation. The results of this study indicate that the presence of intrahepatic antibodies in unmutated germline configuration is a broad phenomenon in the global antibody repertoire generated from total RNA derived from whole\u2010liver tissue that is strongly associated with ALF, suggesting a major role of T cell\u2013independent humoral immunity in the pathogenesis of ALF.<\/jats:p>","DOI":"10.1111\/jvh.13290","type":"journal-article","created":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T18:42:45Z","timestamp":1584729765000},"page":"847-851","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Next\u2010generation sequencing of the intrahepatic antibody repertoire delineates a unique B\u2010cell response in HBV\u2010associated acute liver failure"],"prefix":"10.1111","volume":"27","author":[{"given":"Zhaochun","family":"Chen","sequence":"first","affiliation":[{"name":"Hepatic Pathogenesis Section Laboratory of Infectious Diseases National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen\u2010Hsiang","family":"Shen","sequence":"additional","affiliation":[{"name":"Vaccine Research Center National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4174-1983","authenticated-orcid":false,"given":"Ronald E.","family":"Engle","sequence":"additional","affiliation":[{"name":"Hepatic Pathogenesis Section Laboratory of Infectious Diseases National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto","family":"Zamboni","sequence":"additional","affiliation":[{"name":"Liver Transplantation Center Azienda Ospedaliera G. Brotzu Cagliari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Kwong","sequence":"additional","affiliation":[{"name":"Vaccine Research Center National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Purcell","sequence":"additional","affiliation":[{"name":"Hepatic Pathogenesis Section Laboratory of Infectious Diseases National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0556-7711","authenticated-orcid":false,"given":"Patrizia","family":"Farci","sequence":"additional","affiliation":[{"name":"Hepatic Pathogenesis Section Laboratory of Infectious Diseases National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199312163292508"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119037"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.68.3.1651-1659.1994"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2893.2002.00338.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1809028115"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049611"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1003854107"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr507"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology1030895"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt382"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.06.043"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0934-8"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0879-y"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells6040048"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.2.567"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(98)80117-9"}],"container-title":["Journal of Viral Hepatitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.13290","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.13290","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jvh.13290","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.13290","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T06:51:12Z","timestamp":1693896672000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvh.13290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,3]]},"references-count":16,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1111\/jvh.13290"],"URL":"https:\/\/doi.org\/10.1111\/jvh.13290","archive":["Portico"],"relation":{},"ISSN":["1352-0504","1365-2893"],"issn-type":[{"value":"1352-0504","type":"print"},{"value":"1365-2893","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,3]]},"assertion":[{"value":"2019-12-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}