Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies on the quantitative expression of the Major Histocompatibility Complex (MCH) in hepatocytes chronically infected by Hepatitis B Virus (HBV) report that an increased expression of these antigens could be related to a good immunological response. In the present work we analyze the expression of the MCH antigens in cryostatic sections of liver biopsies taken from subjects (19 children) with various forms of HBsAg positive chronic hepatitis. A high expression of HLA class I antigens and a high degree of hepatocyte necrosis was evident in Chronic Active Hepatitis (CAH) and Chronic Lobular Hepatitis (CLH). On the contrary, subjects with histological diagnosis of Chronic Persistent Hepatitis (CPH) showed a low expression of such antigens. There was however, the difference that in subjects with high hepatic cytolysis and high expression of HLA class I antigens, serum HBV-DNA was clearly present in almost all the cases with CAH, but not detectable in all cases with CLH. The expression of HLA class II antigens and of Beta2 microglobulin was the same in all 19 cases. All cases with HBV-DNA positivity with high class I antigen expression had active hepatitis which seems to suggest that all attempts at viral clearance on the part of the immune system have been in vain. We hope our paper will be an additional parameter for evaluating the course of hepatitis during Interferon treatment.
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PMID:Different expression of HLA class I antigens in liver of children with chronic hepatitis B, evaluated by immunohistochemical method. 269 19

The anti-HLA reactivity of sera from 210 heroin addicts was tested by the direct binding with 125I-labeled preparations of HLA class I and class II molecules purified from human B-cell lines of various HLA haplotypes. A high proportion (81.7%) of the sera tested possessed anti-HLA class I and II reactivity. The reactivity did not show any allospecificity and was apparently mediated by antibodies. The control included 100 healthy blood donors, 25 male homosexuals positive for anti-HIV (human immunodeficiency virus) antibodies, and 25 patients positive for HBsAg (hepatitis B surface antigen). Of these controls, only one of the healthy blood donors was positive for anti-HLA reactivity (P much less than 0.001). Among heroin addicts, the reactivity was independent of the presence of either HBsAg or anti-HIV antibodies in the serum.
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PMID:A high proportion of sera of heroin addicts possesses anti-HLA class I and class II reactivity. 333 95

Naturally processed self-peptides bound to human histocompatibility leukocyte antigens (HLA) class I molecules of human hepatocellular carcinoma tissues (HLA-A2.1, -B44, -B13) in vivo were isolated for sequence analysis. Acid-eluted peptides were subjected to reversed-phase high-performance liquid chromatographic separation and single-fraction sequencing was performed by Edman degradation. The peptides were found to be octamers or nonamers and they were derived from the processing of intracellular proteins. Three independent sequences were obtained from HLA-A2.1 molecules. One of the peptides showed sequence homology to the hepatitis B virus (HBV) pre-S protein, one to aldehyde dehydrogenase, and the other to no known protein. Two independent sequences were obtained from HLA-B44, B13 molecules: one showed sequence homology to the human c-abl protein, the other showed no homology to any known protein. A synthetic biotinylated peptide based on the HBV pre-S peptide sequence was confirmed to bind to HLA-A2.1 gene-transfected L cells. These data suggested that peptides potentially recognized by cytotoxic T cells can bind to HLA class I molecules on tumor cells in vivo.
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PMID:Analysis of naturally processed human histocompatibility leukocyte antigen class I-bound peptides from hepatocellular carcinoma tissues in vivo. 749 16

The relationship between binding affinity for HLA class I molecules and immunogenicity of discrete peptide epitopes has been analyzed in two different experimental approaches. In the first approach, the immunogenicity of potential epitopes ranging in MHC binding affinity over a 10,000-fold range was analyzed in HLA-A*0201 transgenic mice. In the second approach, the antigenicity of approximately 100 different hepatitis B virus (HBV)-derived potential epitopes, all carrying A*0201 binding motifs, was assessed by using PBL of acute hepatitis patients. In both cases, it was found that an affinity threshold of approximately 500 nM (preferably 50 nM or less) apparently determines the capacity of a peptide epitope to elicit a CTL response. These data correlate well with class I binding affinity measurements of either naturally processed peptides or previously described T cell epitopes. Taken together, these data have important implications for the selection of epitopes for peptide-based vaccines, and also formally demonstrate the crucial role of determinant selection in the shaping of T cell responses. Because in most (but not all) cases, high affinity peptides seem to be immunogenic, our data also suggest that holes in the functional T cell repertoire, if they exist, may be relatively rare.
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PMID:The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. 752 44

Direct MHC binding assays with radiolabeled peptides and HLA class I-expressing mammalian cells such as EBV-transformed B cell lines and PHA-activated blasts have been developed. Significant binding of the radiolabeled probe could be obtained if the target cells were preincubated overnight at 26 degrees C in the presence of beta 2-microglobulin. Under these conditions, up to a few percent of the HLA molecules expressed by either cell type could be bound by the labeled peptides. With these assays, the degree of cross-reactivity of the A*0201-restricted hepatitis B virus core 18-27 peptide with other A2 subtypes was examined. It was determined that this peptide epitope also binds the A*0202, A*0205, and A*0206 but not A*0207 subtypes. Inhibition experiments with panels of synthetic peptide analogues underlined the similar ligand specificities of the HLA-A*0201, A*0202, and A*0205 alleles. Analysis of the polymorphic residues that help form the B and F pockets of various HLA alleles allowed prediction of binding of the hepatitis B virus core 18-27 epitope to two other HLA alleles (HLA-A*6802 and A*6901). Thus, it appears that a family of at least six different HLA-A molecules may share overlapping ligand specificities (aliphatic residues in position 2 and at the C termini). These results suggest that broadly cross-reactive peptide epitopes can be identified and greatly enhance the prospective feasibility of peptide-based vaccination approaches.
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PMID:Binding of a peptide antigen to multiple HLA alleles allows definition of an A2-like supertype. 752 83

Despite the extensive molecular information on serum-derived human hepatitis B viruses (HBV), liver-derived replicative HBV genomes have remained largely uninvestigated. We have examined the sequences of the entire core antigen (nucleocapsid) of liver-derived HBVs in 15 different hepatoma patients. Bona fide mutations, rather than subtype polymorphism, have been identified based on the high-frequency occurrence of structural differences from wild type at the highly evolutionarily conserved positions, instead of at the positions known to contain genetic heterogeneity among different isolates from different geographic locations. The distribution of these naturally occurring mutations of HBV core gene appears to be nonrandom and is found predominantly within three major (I, IV, and V) and four minor domains (II, III, VI, and VII). In general, domain IV mutations correlate with domain V mutations. The replicative HBV DNAs tend to accumulate a higher number of mutated core domains than the integrated HBV DNAs. At the domain level, there is no significant difference in HBV core mutation frequencies between the liver tumors and the adjacent nontumorous livers. Strikingly, domains I, III, and V coincide with three major known T cell epitopes within the core protein in acute and chronic hepatitis B patients. Furthermore, these domains coincide with HLA class II-restricted T cell epitopes, rather than with the conventional HLA class I-restricted epitopes of cytotoxic T lymphocytes. Our results support the hypothesis that HBV core antigen variants can accomplish immunoevasion via accumulated escape mutations. In addition, they also provide a potential molecular explanation for the maintenance of persistent infection of human hepatitis B virus in chronic carriers.
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PMID:Core antigen mutations of human hepatitis B virus in hepatomas accumulate in MHC class II-restricted T cell epitopes. 754 53

Irreversible ductopenic rejection (DR) after orthotopic liver transplantation (OLT) is a major cause of late hepatic allograft failure. A variety of risk factors for DR have been postulated, but they are controversial. All transplant recipients at our institution with graft survival of more than 1 month (n = 120) were examined retrospectively with a view to possible risk factors for DR. These factors included age, sex, underlying liver disease, hepatitis B and C infections, donor-recipient CMV status, post-OLT CMV infections, immunosuppressive regimen, ABO blood type, and HLA class I and class II mismatches. Statistical analysis was performed with the univariate chi-square test or the two-tailed Fischer's exact test. Ten patients (8.3%) developed DR. Seventeen patients had HCV infections after OLT. In this group, the incidence of DR was highest (4 of 17, or 23.5%). This was significantly higher than for all other OLT groups (6 of 103 patients, or 5.8%; P < 0.03). The other factors analyzed did not reach statistical significance, including those that other authors found important for the development of DR. It may well be that hepatitis C infection predisposes one to the development of DR after OLT.
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PMID:Hepatitis C virus infection as a possible risk factor for ductopenic rejection (vanishing bile duct syndrome) after liver transplantation. 757 16

To determine the relationship between hepatitis B virus (HBV) replication and HLA antigen display at a cellular level, the hepatic expression of HLA antigens and HBV genome (HBV-DNA)/gene products (HBsAg/HBcAg) was studied in 24 patients with chronic HBV infection using simultaneously immunohistochemistry and nonisotopic in situ hybridization. The effect of interferon-alpha and interferon-gamma on hepatocyte HLA antigen expression was also evaluated using primary hepatocyte culture in eight patients with chronic HBV infection. HLA class I antigens were detected on hepatocyte membrane in 23 patients (95.8%). Hepatocytes positive for HBcAg and HBV-DNA (cytoplasmic +/- nuclear) were either negative or only faintly positive for HLA class I antigens, while hepatocytes positive for HBsAg showed similar levels of HLA class I antigen expression compared with those hepatocytes with no HBsAg expression. In contrast, hepatocytes adjacent to inflammatory infiltrates, whether positive for HBV-DNA or HBV antigens or not, were always strongly positive for HLA class I antigens. Furthermore, active liver histology (N = 12) was associated with a higher overall level of hepatic HLA class I antigen expression as compared with inactive histology (N = 12, P = 0.003). Both interferon-alpha and interferon-gamma treatment in vitro enhanced hepatocyte HLA class I antigen expression. These data indicate that expression of HLA class I antigens is not enhanced on the membrane of hepatocytes with HBV replication, and this may be one factor that permits the development of viral persistence.
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PMID:Hepatic HLA antigen display in chronic hepatitis B virus infection. Relation to hepatic expression of HBV genome/gene products and liver histology. 768 63

Inasmuch as the hepatitis B virus (HBV) is not directly cytopathic for the infected hepatocyte, it is generally presumed that viral clearance and liver cell injury during viral hepatitis are due to a CTL response to HBV encoded Ag presented by HLA class I molecules. We have previously examined the peripheral blood CTL response to two HBV nucleocapsid epitopes in patients with acute and chronic viral hepatitis, one of which is restricted by HLA-A2, whereas the other is dually restricted by HLA-A31 and Aw68. In this study, we defined the HLA-A2-restricted CTL response to the hepatitis B surface Ag (HBsAg) by using a panel of HBsAg-derived synthetic peptides containing the ideal HLA-A2.1 binding motif (-L------V). Several novel aspects of HBV immunobiology and pathogenesis are evident from this study. First, the peripheral blood CTL response to HBV-encoded Ag is remarkably polyclonal and multispecific in most patients with acute hepatitis. Indeed, HLA-A2-restricted CTL specific for as many as four envelope epitopes and one nucleocapsid epitope were found to be present simultaneously in individual patients with acute viral hepatitis. Second, HBV-specific CTL are not detectable in the peripheral blood in a minority of patients with acute hepatitis, nor have we detected a CTL response in any of the patients with chronic hepatitis that we have studied thus far. Although the cellular and molecular basis for CTL nonresponse remains to be determined, the data suggest that it may contribute to viral persistence. Third, the diversity and the specificity of the CTL response is determined in part by the coding sequence of the viral genome present in each infected patient. Indeed, the apparent nonresponse of some acutely infected patients to at least one HBsAg-specific CTL epitope actually reflects infection by a viral variant that contains a critical substitution in one of the anchor residues within the epitope. Finally, at a fundamental level, the data suggest that the presence of the HLA-A2.1-binding motif in a peptide may not be sufficient for binding; and the capacity of a peptide to bind the class I molecule does not guarantee that it will be immunogenic.
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PMID:HLA A2 restricted cytotoxic T lymphocyte responses to multiple hepatitis B surface antigen epitopes during hepatitis B virus infection. 768 26

Cytotoxic T lymphocyte (CTL) activity for hepatitis B virus (HBV) DNA-transfected HepG2 cells (designated HB3-5), which secrete HBsAg, HBeAg and HBV particles, was investigated in 31 patients with chronic HBV infection (18 chronic hepatitis and 13 asymptomatic carriers). 51Cr-labeled HB3-5 with A2 as a major HLA class I antigen served as target cells and T cells from peripheral blood mononuclear cells as effector cells. The CTL activity was measured by a 51Cr release assay. Patients were divided into two groups, the A2 group bearing HLA-A2 and the non-A2 group not bearing HLA-A2. Chronic hepatitis patients in the A2 group showed increased HBV Ag-specific cytotoxicity compared with that seen in the non-A2 group (5.2 +/- 3.1% vs. 0.9 +/- 1.4%; means +/- SD, P < 0.01). In the A2 group with chronic hepatitis, the cytotoxicity was greater in anti-HBe positive patients than in HBeAg positive patients (8.6 +/- 1.9% vs. 3.4 +/- 2.0%, P < 0.01), and asymptomatic carriers showed less cytotoxicity (0.35 +/- 0.31%, P < 0.001) compared with chronic hepatitis patients. In the non-A2 group, HBV Ag-specific CTL activity was negligible in most patients and thus no differences were found among all patient groups. The HBV Ag-specific cytotoxicity was inhibited by antibodies to CD3, HLA class I and hepatitis B nucleocapsid antigens. Removal of CD8+ cells also resulted in marked decrease in the cytotoxicity. These findings indicate that HBV Ag-specific cytotoxicity reflects liver cell damage and HBeAg/anti-HBe status. Furthermore, our assay system appears to be useful to assess CTL response in patients with chronic HBV infection.
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PMID:Cytotoxic T lymphocyte activity to hepatitis B virus DNA-transfected HepG2 cells in patients with chronic hepatitis B. 769 38


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