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)

Although the mechanism of susceptibility to chronic persistent hepatitis B virus (HBV) infection is not well clarified, immunogenetic factors of the host may have a role. Recently, a strong association between HLA-DR13 and the self-limited course of HBV infection has been reported. To determine whether the elimination of HBV is related to a particular HLA allele, we studied the HBV markers and HLA-DR phenotypes of 1,272 Koreans who had visited Yonsei University Medical Center for renal transplantation. They included 330 renal transplant donors. Subjects were categorized into 3 different groups: the "Unexposed Group" (UE; n = 946) with negative HBV markers, the "Chronic Carrier Group" (CC; n = 83), who were hepatitis B surface antigen (HBsAg)-positive, and the "Spontaneously Cleared Group" (SC; n = 243), who were HBsAg-negative with antibodies to HBsAg (anti-HBs) and hepatitis B core antigen (anti-HBc). HLA-DR4 was the most common type in all groups. HLA-DR6 was significantly more frequent in 69 of 243 subjects with SC (28. 4%) than in 8 of 83 subjects with CC (9.6%) (P <.001; relative risk [RR] = 3.72). HLA-DR9 was significantly more frequent in CC than in SC (P <.001; RR = 0.33). HLA-DR13 showed a stronger association with the clearance of HBV than the other HLA-DR6 subgroup. The distribution of HLA-DR phenotypes was similar regardless of renal disease. Our data indicate that HLA-DR6, especially HLA-DR13, is one of the host factors, which influences the immune response to HBV, and may be associated with self-elimination of HBV in Koreans.
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PMID:Association between hepatitis B virus infection and HLA-DR type in Korea. 1082 65

In designing epitope-based vaccines, the inclusion of a helper T-lymphocyte (HTL) epitope is necessary to elicit both humoral and cellular immune responses. Whereas the preS region of the hepatitis B virus (HBV) surface antigen is well-known to raise protective immunity, the epitopes for activating HTLs are poorly characterized. In an attempt to identify such epitopes, the HBV-preS region was screened for peptide sequences with HLA-DR4 binding motifs, and putative HTL candidate peptides were synthesized in a biotinylated form. Using L929 mouse fibroblasts stably transfected with HLA-DRB1*0405 and HLA-DRA*0101 cDNA, specific binding of the peptides was then detected using fluorescence-conjugated streptavidin. The cell-surface expression of HLA-DR molecules on transfectants was confirmed by confocal microscopy, and quantitative analysis of candidate peptide binding was performed by fluorescence activated cell sorting. Among eight preS-derived peptides, three candidate peptides-namely preS1(23-33), preS1(62-72), and preS1(76-86)-showed good binding characteristics to HLA-DR4 molecules, among which the preS1(23-33) epitope was regarded as the most promising HTL epitope. Further studies with these candidate HTL stimulatory peptides will show their ability to activate the human immune system against HBV.
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PMID:In vitro binding analysis of hepatitis B virus preS-derived putative helper T-cell epitopes to MHC class II molecules using stable HLA-DRB1*0405/DRA*0101 transfected cells. 1132 11

CD4(+) T cells play a major role in the host defense against viruses and intracellular microbes. During the natural course of such an infection, specific CD4(+) T cells are exposed to a wide range of antigen concentrations depending on the body compartment and the stage of disease. While epitope variants trigger only subsets of T-cell effector functions, the response of virus-specific CD4(+) T cells to various concentrations of the wild-type antigen has not been systematically studied. We stimulated hepatitis B virus core- and hepatitis C virus NS3-specific CD4(+) T-cell clones which had been isolated from patients with acute hepatitis during viral clearance with a wide range of specific antigen concentrations and determined the phenotypic changes and the induction of T-cell effector functions in relation to T-cell receptor internalization. A low antigen concentration induced the expression of T-cell activation markers and adhesion molecules in CD4(+) T-cell clones in the absence of cytokine secretion and proliferation. The expression of CD25, HLA-DR, CD69, and intercellular cell adhesion molecule 1 increased as soon as T-cell receptor internalization became detectable. A 30- to 100-fold-higher antigen concentration, corresponding to the internalization of 20 to 30% of T-cell receptor molecules, however, was required for the induction of proliferation as well as for gamma interferon and interleukin-4 secretion. These data indicate that virus-specific CD4(+) T cells can respond to specific antigen in a graded manner depending on the antigen concentration, which may have implications for a coordinate regulation of specific CD4(+) T-cell responses.
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PMID:Different levels of T-cell receptor triggering induce distinct functions in hepatitis B and hepatitis C virus-specific human CD4(+) T-cell clones. 1148 23

Liver transplantation (OLT) for end-stage chronic hepatitis-B-virus (HBV) infection is frequently complicated by HBV recurrence. In the present study we investigated whether human leucocyte antigen (HLA)-matching influences the outcome after OLT. In a retrospective analysis we reviewed 84 recipients of liver transplants for end-stage HBV-cirrhosis and complete HLA-typing for outcome after OLT. Follow-up ranges from 1 to 110 months (median = 55.6 months). Immunosuppression consisted of Cyclosporin A (CsA)-based quadruple induction therapy or Tacrolimus-based induction protocols. Immunoprophylaxis with hepatitis B immunoglobulin was started at OLT and continued long-term. Actuarial 1- and 5-yr graft survival figures were 90.5 and 80.4%, respectively. Hepatitis-B recurrence was responsible for 15 of 20 (75%) graft failures. We observed a significantly improved graft survival in patients with more HLA-A, -B compatibilities (p = 0.02), whereas the degree of HLA-DR compatibilities did not influence the outcome. The occurrence of HBV-reinfection was significantly lower in HLA-A, -B matched grafts (p < 0.05). Additionally, graft survival was prolonged in patients with HBV-reinfection and 1 or 2 HLA-B compatibilities when compared with patients with HBV-reinfection and a complete HLA-B mismatch (p = 0.02). In conclusion, this retrospective analysis shows that more HLA-A, -B compatibilities seems to be associated with an improved graft survival in patients after OLT for end-stage HBV infection.
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PMID:Impact of HLA-compatibilities in patients undergoing liver transplantation for HBV-cirrhosis. 1196 82

A phase I/II clinical trial was carried out to determine the safety of Flt3 ligand used as a vaccine adjuvant when administered to healthy human volunteers on two different schedules. In the first phase of this study, Flt3 ligand was administered SQ at a dose of 20 microg/kg (to a maximum of 1500 microg) every day (N=10) or every other day (N=10) for 1 week. The Flt3 ligand injection series was followed 1 day later by the first of three vaccinations with the licensed hepatitis B vaccine. In the second phase of the trial, 30 volunteers received either Flt3 ligand or placebo on the alternate day schedule in a randomized, double-blind design. The Flt3 ligand injections were safe and very well-tolerated. The number of lineage negative, HLA-DR(hi), CD11c(+), CD123(-) dendritic cells (DCs) increased 23-fold, and the lineage negative, HLA-DR(hi), CD11c(-), CD(123 bright) pre-DCs increased 6-fold. There was an associated increase in monocytes and WBCs in the Flt3 ligand recipients. Despite the marked increase in peripheral circulating dendritic cells, no increase was observed in the hepatitis B antibody titers induced after vaccination.
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PMID:The use of Flt3 ligand as an adjuvant for hepatitis B vaccination of healthy adults. 1245 Jul 8

Dendritic cell (DC) maturation is critical for the induction of antigen-specific T lymphocyte responses and may be essential for the development of human vaccines relying on T cell immunity. We investigated the effects on human DC of OM-197, a synthetic pseudodipeptide derived from amino acids, linked to three fatty acid chains and devoid of endotoxin properties. OM-197 upregulated the expression of HLA-DR, CD80, CD86, CD83, CD40 and CD54 at the surface of myeloid DC naturally present in blood as well as of DC generated in vitro from monocytes using IL-4 and GM-CSF. OM-197 also induced the release of IL-12 and TNF-alpha from DC. Finally, DC incubated with OM-197 after pulsing with hepatitis B surface antigen (HBs Ag) induced in vitro expansion of IFN-gamma-secreting HBs Ag-specific CD4(+) T lymphocytes from naive individuals. Taken together, these data identify OM-197 as a potential vaccine adjuvant for the induction of Th1-type responses.
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PMID:OM197-MP-AC induces the maturation of human dendritic cells and promotes a primary T cell response. 1263 19

Hepatitis B (HB) in haemodialysis patients results in morbidity and mortality, through chronicity, which leads to cirrhosis and liver carcinoma, even after renal transplantation. Hepatitis B vaccination is protective against HB virus infection. Suppressed immunity in renal failure leads to low HB vaccination success rates. Uremia, inadequate dialysis, use of low biocompatibility dialysis material, hyperparathyroidism, anemia, iron overload and malnutrition are all factors contributing to depressed immunity. Renal failure, associated with chronic inflammation, leads to impaired monokine production which results in decreased immunity. This impairment could result from defective HLA-DR B7-2 expression on monocytes. Hepatitis B vaccination non-responders express increased levels of HLA class II alleles (T-cell immune response modulators) DRB1 01 (DR1) and DRB1 15 (DR15). Various methods have been used to enhance the immune response to HB vaccination such as recombinant adjuvants, thymopentine, IL-2, levamisole and GM-CSF: they have produced variable results. Better dialysis biocompatibility and adequacy have also been conducted to overcome this low immune response. Response to conventional intramuscular HB vaccination is considered an index of adequate dialysis and low inflammatory state, both associated with better cardiovascular outcome and survival. HB vaccination reinforcement techniques evolved from an initial intramuscular double/multiple-dosing regimen to more frequent intradermal smaller dose injection. This newer regimen achieves a higher and almost complete seroconversion rate, although frequent boosters shots are necessary to maintain protective levels. Experience with pre-S1/S2, third generation, vaccines is limited and they have not been proven to be more effective than intradermally administered S antigens. Recombinant HB vaccines, intradermally administered, have been shown to elicit an immune response in all renal failure patients. Additionally the use of recombinant erythropoietin treatment to correct anemia contributes to this success.
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PMID:Recombinant hepatitis B vaccination in renal failure patients. 1267 88

We analyzed the prevalence and longitudinal fluctuation of hepatitis B virus (HBV)-specific CD8 T cells in chronic HBV infection using an HLA-A2-HBc18-27 tetramer. Thirty-five HLA-A2-positive patients with chronic HBV infection were divided into 17 HBe antigen (HBeAg)-positive and 18 anti-HBe antibody (anti-HBe)-positive patients. Five HLA-A2-positive normal subjects, five HLA-A2-negative patients with chronic HBV infection, and two HLA-A2-positive patients with acute HBV infection were included as controls. HBc18-27-specific CD8 T cells (c18-27-CD8Ts) were detected at a significantly higher prevalence in patients with anti-HBe (6/18) than in those with HBeAg (1/17), and their frequency reached 0.28% of the total CD8 T cells. The prevalence was significantly higher in patients with HBV DNA below 4.0 log genome equivalents (LGE)/ml (5/12) than in those with HBV DNA above 4.0 LGE/ml (2/23). The frequency of c18-27-CD8Ts was consistently higher in liver-infiltrating lymphocytes, ranging from 0.18 to 1.28%, than in autologous peripheral blood lymphocytes. Longitudinal analysis of patients with acute flare-up demonstrated that the elevation of alanine aminotransferase (ALT) was intimately associated with the expansion of c18-27-CD8Ts. Phenotypic analysis revealed that most c18-27-CD8Ts during acute flare-up expressed HLA-DR and CCR5, while those during low-ALT periods showed low expression. Furthermore, most liver-infiltrating c18-27-CD8Ts were positive for HLA-DR and CCR5, suggesting selective recruitment of activated c18-27-CD8Ts into the liver. In conclusion. HBV-specific CD8 T cells play an important role in the suppression of virus replication, and acute flare-up is associated with the expansion and activation of HBV-specific memory cells.
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PMID:HBcAg-specific CD8 T cells play an important role in virus suppression, and acute flare-up is associated with the expansion of activated memory T cells. 1279 44

Hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN) is occurring at high prevalence in most Asian endemic areas. There have been some reports on human leucocyte antigen (HLA) associations with HBV infections; however, HLA association with HBV-GN has been rarely reported. Forty-six adult Korean patients with HBV-GN (42 male and four female patients, age 20-66), 100 HBsAg (-) healthy controls, and 89 individuals with chronic HBV infection were studied for HLA-DRB1 and DQB1 gene polymorphisms using high-resolution DNA typing methods. In HBV-GN patients, a strong association with HLA-DR2 was observed compared with HBsAg (-) controls (OR = 4.0). Different HLA-DR2 alleles were associated with different pathologic subtypes of HBV-GN: DRB1*1502 with membranoproliferative glomerulonephritis (MPGN, n = 35) (OR = 14.5) and DRB1*1501 with membranous nephropathy (MN, n = 11) (OR = 3.8). HLA-DQB1*0601, strongly linked to DRB1*1502, was also associated with MPGN subtype of HBV-GN (OR = 4.3). All these associations were also significant compared with chronic HBV infection group. For chronic HBV infection per se, DRB1*1302, DQB1*0402, and DQB1*0604 had some protective effect (OR = 0.4, OR = 0.3, and OR = 0.1, respectively), and DRB1*1101 was weakly associated (OR = 4.6) in Koreans. These results suggest that HLA-DR or related genetic factor is associated with disease susceptibility to HBV-GN in Koreans, and different pathologic subtypes of HBV-GN are influenced by the genetic factors of the patients.
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PMID:Two subtypes of hepatitis B virus-associated glomerulonephritis are associated with different HLA-DR2 alleles in Koreans. 1461 34

Vaccination using surface antigen from hepatitis B virus has not been successfully responded by hemodialysis patients. The present study was aimed at assessing a possible relationship between human leukocyte antigens and the low production of protective antibodies (anti-HbS) against the surface antigen from hepatitis B by patients with chronic renal failure submitted to hemodialysis programs. The antigens HLA-DR and HLA-DQ were identified in 76 hemodialysis patients through classic microlymphotoxicity. Our results showed that 34.2% of the patients were non-responsive to the vaccine VHB. The most frequent HLA specificity were: HLA-DR3, DR-7 and DQ2 with a significant association for HLA-DR3 (p=0.0025; OR 5.1; IC 95% 1.36-19.10). Such data suggest an association between genes from HLA class II antigens and the humoral non-response to the vaccine VHB.
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PMID:[Association of humans leucocitary antigens with humoral nonresponsive to hepatitis B vaccine in chronic hemodialysis patients]. 1504 75


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