title: Humoral and cellular immune responses to hepatitis B vaccination in hepatitis B surface antigen-carrier children who cleared serum-hepatitis B surface antigen.
abstract: The immune responses to hepatitis B vaccine were studied in 11 hepatitis B surface antigen (HBsAg) carrier children who had cleared HBsAg but failed to develop hepatitis B surface antigen antibodies (anti-HBs) in sera (group 1), 5 HBsAg carrier children who had cleared HBsAg and developed detectable anti-HBs in sera (group 2), and 5 healthy subjects seronegative for all hepatitis B virus (HBV) markers (group 3). After receiving three doses of HB vaccine, group 1 subjects failed to develop detectable anti-HBs. Subsequently, each subject of the three groups was given one dose of the same vaccine for a cellular immunity study, and a measurable proliferation of peripheral blood mononuclear cells (PBMC) to HBsAg was detected in 1 of 8 (12.5%), 0 of 5, and 4 of 5 (80%) of the cases in each group, respectively, after vaccination. The removal of CD8+ cells enhanced the HBsAg blastogenic response in group 3 but did not reverse the unresponsiveness in group 1 and group 2 subjects. The addition of interleukin (IL)-2 in culture reversed unresponsiveness in all cases except one case in group 1. Compared with before vaccination, PBMC from group 2 subjects produced significantly less interferon gamma (IFN-gamma) and more IL-4 in response to HBsAg after vaccination, a cytokine response not observed in group 1 subjects. HLA typing indicated that 3 of 10 patients in group 1 (30%) and 1 of 5 patients in group 2 (20%) had HLA-DRw14-DRw52, a marker previously linked to low anti-HBs response to hepatitis B vaccine in Taiwan. We conclude that the underlying causes of poor anti-HBs response in group 1 subjects are multifactorial, including specific failure of antigen presentation or T-cell activation, or the lack of T helper (Th)2 cell-like response to HBsAg. HLA-DRw14-DRw52 does not confer absolute nonresponsiveness to HBsAg. These patients are not benefited by hepatitis B immunization.
authors.affiliation: Department of Emergency Medicine, College of Medicine, National Taiwan University, Taipei.
authors.forename: H Y
authors.initials: HY
authors.lastname: Hsu
authors.forename: M H
authors.initials: MH
authors.lastname: Chang
authors.forename: R P
authors.initials: RP
authors.lastname: Hsieh
authors.forename: Y H
authors.initials: YH
authors.lastname: Ni
authors.forename: W K
authors.initials: WK
authors.lastname: Chi
mesh_terms: D000293:Adolescent; D000328:Adult; D000917:Antibody Formation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002353:Carrier State / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D016207:Cytokines / Q000096:biosynthesis; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006683:HLA-DQ Antigens / Q000097:blood; D006684:HLA-DR Antigens / Q000097:blood; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000096:biosynthesis / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology; D017325:Hepatitis B Vaccines; D006515:Hepatitis B virus / Q000302:isolation & purification; D006650:Histocompatibility Testing; D006801:Humans; D007111:Immunity, Cellular; D007115:Immunization Schedule; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D016133:Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D004279:DNA, Viral; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D015847:Interleukin-4; D007371:Interferon-gamma