title: T- and B-cell responses and previous exposure to hepatitis B virus in 'anti-HBc alone' patients.
abstract: A serologic response to hepatitis B virus (HBV) defined as 'anti-HBc alone' is commonly observed, but its significance remains unclear. This study aimed to define the relationship between 'anti-HBc alone' serostatus and HBV infection, including HBV-specific T- and B-cell memory responses. We enrolled 31 'anti-HBc alone' patients. Total HBV DNA and cccDNA were tested by nested polymerase chain reaction (PCR) analysis in liver samples from 22 'anti-HBc alone' patients vs controls (chronic or resolved HBV infection), followed by HBsAg/HBcAg immunohistochemical (IHC) staining. IFN-γ secretion by HBV-specific T cells was compared in individuals who were 'anti-HBc alone' (n = 27), resolved HBV (n = 21), chronic HBV (n = 24) and 12 healthy controls using enzyme-linked immunospot (ELISpot) assays. An HBsAg-IgG B-cell ELISpot assay was performed in 'anti-HBc alone' patients before and after one dose of recombinant HBsAg vaccine. The majority (23/31, 74.2%) of the 'anti-HBc alone' individuals were co-infected with HCV. Infrequent intrahepatic total HBV DNA (2/22, 9.1%) and cccDNA (1/22, 4.5%) were detected in biopsies; HBsAg and HBcAg IHC staining was negative. HBV-specific T-cell responses were similar between 'anti-HBc alone' individuals and HBV resolvers. Circulating HBV-memory B-cell responses were detected in all 'anti-HBc alone' individuals, consistent with an HBsAg-specific memory pool. After one HBV vaccine dose, increased anti-HBs antibody levels were observed, accompanied by an expansion of HBsAg-specific memory B cells (P = 0.0226). 'Anti-HBc alone' individuals showed HBV-specific T-cell and memory B-cell responses typical of previous viral exposure and protective memory, suggesting a resolved infection.
authors.affiliation: Hepatology, Department of Clinical Research, Inselspital, University of Bern, Bern, Switzerland.|State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Hepatology, Department of Clinical Research, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Sachse
authors.affiliation: Department of Nephrology, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Semmo
authors.affiliation: Hepatology, Department of Clinical Research, Inselspital, University of Bern, Bern, Switzerland.|Department of Hepatology, Inselspital, University Clinic of Visceral Surgery and Medicine, Bern, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Lokhande
authors.affiliation: Institute of Pathology, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Montani
authors.affiliation: Hepatology, Department of Clinical Research, Inselspital, University of Bern, Bern, Switzerland.|Department of Hepatology, Inselspital, University Clinic of Visceral Surgery and Medicine, Bern, Switzerland.
authors.forename: J-F
authors.initials: JF
authors.lastname: Dufour
authors.affiliation: Inserm, U1052, UMR CNRS 5268, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
authors.forename: F
authors.initials: F
authors.lastname: Zoulim
authors.affiliation: Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.
authors.forename: P
authors.initials: P
authors.lastname: Klenerman
authors.affiliation: Hepatology, Department of Clinical Research, Inselspital, University of Bern, Bern, Switzerland.|Department of Hepatology, Inselspital, University Clinic of Visceral Surgery and Medicine, Bern, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Semmo
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D006510:Hepatitis B Antibodies / Q000097:blood / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000032:analysis / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000032:analysis / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007371:Interferon-gamma
keywords: T cells; anti-HBc alone; hepatitis B; memory B cells