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)

We investigated the effects of interferon therapy on hepatocyte human leukocyte antigen class I and class II antigen expression and intrahepatic lymphocyte subsets in patients with chronic viral hepatitis B (n = 11) and C (n = 10). Interferon-alpha was administered intramuscularly in doses ranging from 3 to 18 million international units daily for 4 wk. Liver biopsy specimens were obtained just before and immediately after treatment, and the specimens were stained by the indirect immunoperoxidase method for evaluation of human leukocyte antigen expression and lymphocyte subsets. Before therapy, no significant difference was noted between hepatitis B and C in human leukocyte antigen class I antigen expression on hepatocytes or in the lymphocyte subsets in the intralobular and portal areas. After interferon-alpha treatment, hepatocyte expression of human leukocyte antigen class I antigens and serum beta 2-microglobulin levels were virtually unchanged in chronic viral hepatitis C patients, but both were increased in chronic viral hepatitis B patients. Human leukocyte antigen class II antigens were not expressed during treatment. The mean number of intralobular CD3+ and CD8+ cells and the mean serum ALT level decreased significantly in chronic viral hepatitis C patients (p less than 0.05) but not in chronic viral hepatitis B patients. The mean number of intralobular CD4+ cells was unaffected by interferon therapy in both groups. In all 21 patients, the changes in CD8+ cell numbers paralleled the changes in serum ALT levels. Our findings suggest that T-cell cytotoxicity may play an important role in hepatocyte damage in both chronic viral hepatitis C and chronic viral hepatitis B and that the response to interferon-alpha differs in these two types of hepatitis.
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PMID:Effects of interferon on intrahepatic human leukocyte antigens and lymphocyte subsets in patients with chronic hepatitis B and C. 171 Oct

The hepatitis B virus (HBV) and polyomavirus (Py) enhancer regions contain multiple cis-acting elements that contribute to enhancer activity. The EF-C binding site was previously shown to be an important functional component of each enhancer region. EF-C is a ubiquitous binding activity that interacts with an inverted repeat sequence in the HBV and Py enhancer regions. Although the EF-C binding site is required for optimal enhancer function, the EF-C site does not possess intrinsic enhancer activity when assayed in the absence of flanking elements. With both the HBV and Py enhancer regions, EF-C stimulates the activity of adjacent enhancer elements in a synergistic manner. EF-C corresponds to RFX-1, a protein that binds to a conserved and functionally important site in major histocompatibility complex (MHC) class II antigen promoter regions. Interestingly, the RFX-1 binding site in MHC class II promoters only contains an EF-C half-site, maintaining one arm of the inverted repeat in an EF-C binding site. We have investigated the binding of purified EF-C and RFX-1 to sites in the Py and HBV enhancer regions that carry mutations that either disrupt one arm of the EF-C inverted repeat, or alter the spacing between the repeats. Our results show that the interaction of EF-C and RFX-1 with an intact inverted repeat is required for functional activity of these viral enhancer regions. Chemical footprinting and modification interference assays show that the interaction of EF-C and RFX-1 with the DRA MHC class II promoter truly represents half-site interaction, and that this binding is unstable. In contrast, the binding of EF-C and RFX-1 to the viral inverted repeats is stable. These results suggest that an additional activity may be required to stabilize EF-C/RFX-1 interaction with the MHC class II promoter, and that viral enhancer regions have evolved high affinity binding sites to sequester dimeric EF-C/RFX-1.
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PMID:Interaction of EF-C/RFX-1 with the inverted repeat of viral enhancer regions is required for transactivation. 771 44

The experiments presented here were performed to see whether the level of expression of major histocompatibility complex (MHC) class II antigen (Ia antigen) on dendritic cells, one of the most critical antigen presenting cells (APC), influences the humoral immune response in hepatitis B virus (HBV) transgenic mice. We have reported that transgenic mice had a low responsiveness in specific antibody production to keyhole limpet haemocyanin (KLH), a T-cell dependent, HBV-unrelated antigen compared with the age, sex, and major histocompatibility-matched normal mice, due to a significantly lower T-cell stimulatory capacity of transgenic mice-derived dendritic cells, possibly as a result of significantly lower level of Ia antigen. Immunohistochemical staining has shown that treatment of transgenic mice with mouse recombinant interferon-gamma (IFN-gamma), daily for six consecutive days resulted in an increased expression of Ia antigen on splenic dendritic cells. Again, flow cytometric analyses have further confirmed the significant increase in the expression of Ia antigen on dendritic cells, isolated from transgenic mice treated with IFN-gamma compared with the same from the untreated or phosphate-buffered saline (PBS)-treated transgenic mice. Transgenic mice immunized with two optimum doses of KLH (5 micrograms/mouse) could not produce anti-KLH antibodies in sera, but injecting transgenic mice with the same doses of KLH together with IFN-gamma resulted in the production of anti-KLH antibodies in sera. Again, KLH-primed normal mice-derived T/B lymphocytes produced anti-KLH antibody, when cultured with dendritic cells from IFN-gamma-treated transgenic mice expressing a higher level of Ia antigen, but not with the same from PBS-treated or untreated transgenic mice. Treatment of transgenic mice with IFN-gamma resulted in a reduced level of hepatitis B virus (HBV) DNA in liver and in sera. These experiments have shown that the level of expression of Ia antigen on dendritic cells is a critical factor for its APC capability and its modulation of IFN-gamma may be used for immune therapy in HBV carriers.
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PMID:Upregulation of MHC class II antigen on dendritic cells from hepatitis B virus transgenic mice by interferon-gamma: abrogation of immune response defect to a T-cell-dependent antigen. 867 4

Human leucocyte antigen (HLA) associations have been reported in children with hepatitis B virus (HBV) associated membranous nephropathy (MN). In a previous study, we found an association with HLA DQB1*0603 in black children with HBVMN. To determine whether HLA DQB1*0603 predisposes to HBV carriage and development of abnormal proteinuria, we studied 70 family members of 14 children with HBVMN positive for HLA DQB1*0603. HBV was determined using third generation ELISA, slot-blot hybridisation, and nested polymerase chain reaction. HLA class I antigens were determined using a two-staged lymphocytotoxic test whereas class II antigen typing was done using sequence-specific primers. Abnormal proteinuria was defined by a protein/creatinine ratio > or =0.2. Associations of HLA DQB1*0603 with HBV carriage and abnormal proteinuria were determined using the mean probability ratio (LOD scores). Forty-seven (67%) family members were positive for HBV infection. Nineteen (27%) had abnormal range proteinuria. LOD scores in the study subjects with DQB1*0603 who were HBV negative versus those with DQB1*0603 who were HBV positive was not significant (anti-log sum =2.0559 and average 0.23). When a similar calculation was made for abnormal proteinuria, there were no significant findings (anti-log sum =3.8587 and average 0.43). This lack of association of HLA DQB1*0603 with either HBV carriage or abnormal proteinuria in family members suggests that additional factors may play a role in predisposing children to chronic HBV carriage and the development of MN. We therefore conclude that the main effect of HLA DQB1*0603 that distinguishes family members from HBVMN is the degree of proteinuria, which is a reflection of the severity of glomerular basement membrane damage in the latter.
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PMID:HLA associations with HBV carriage and proteinuria. 1221 25

Disulfide reduction is an important step in antigen processing for HLA class II restricted T cell responses. Migration inhibitory factor (MIF) is a member of the thioredoxin family and has been classically defined as a cytokine. Using enzyme-linked immunosorbent assay and CD analysis, here we describe the binding to MIF of two peptides, hepatitis B surface antigen (HBsAg) and insulin B (InsB) with high affinity for HLA class II allo-types, HLA-DP2 and HLA-DQ8, respectively. At neutral pH, cysteinylated InsB was a substrate for MIF thiol reductase activity, as assessed by mass spectroscopy/electrospray analysis. Finally, a biologically active form of MIF co-immunopurified with mature forms of HLA DP2/15, and a peptide derived from the HLA-DP beta1 helix could be used for affinity purification of MIF. The possibility that MIF participates in class II antigen presentation and/or as a chaperone is discussed.
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PMID:Molecular interaction and enzymatic activity of macrophage migration inhibitory factor with immunorelevant peptides. 1274 Mar 74