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)

The HLA multigene family consists of HLA class I (HLA-A, B and C) and class II (HLA-DR, DQ and DP) genes, and plays a central role in the regulation of immune response. To investigate how each HLA gene and each HLA allele contribute to the human immune response, we immunized 339 healthy Japanese medical students with recombinant hepatitis B surface antigen (rHBsAg) and determined the HLA types of all vaccinated subjects at the DNA level. The anti-HBs antibody titers showed a log-normal distribution, implying that the immune response to HBsAg in humans is a multifactorial and continuous trait. A stepwise multiple regression analysis demonstrated the alleles at the HLA-class I (HLA-A and B) and class II (HLA-DRB1, DQA1, DQB1, DPA1 and DPB1) loci significantly contributed to antibody production to HBsAg. The predicting equation of anti-HBs antibody levels for individuals with any HLA phenotype was proposed based on a multiple regression analysis. The multiple correlation coefficient of antibody production to HBsAg with the HLA-DRB1 locus was highest (0.34) among all of the HLA loci, whereas those with whole HLA class I or class II loci were 0.36 or 0.44 respectively. The incorporated correlation coefficient of the presence of all HLA gene families with antibody production became 0.50, suggesting that HLA class I and class II loci within the HLA multigene family are dynamically involved in regulation of the immune response to HBsAg.
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PMID:Contribution of HLA class I and class II alleles to the regulation of antibody production to hepatitis B surface antigen in humans. 867 39

We present here the analysis of 86 individuals who were true antibody nonresponders to a vaccine containing hepatitis B surface antigen. The HLA type of these individuals and of 248 controls were determined by serology for HLA class I and by molecular typing for the HLA class II loci DRB1 and DQB1. Subsequent analysis of the results revealed that HLA-DRB1*0701 and HLA-DQB1*02 were significantly associated with antibody non-response to the "S"-containing vaccine compared with the HLA control population. Further, we found that the antibody non-response was also significantly associated with the above antigens when found in linkage disequilibrium on the HLA haplotype DRB1*0701; DQB1*0202. The hepatitis B surface antigen vaccine antibody nonresponder group, comprising 86 individuals, were revaccinated with a novel vaccine Hep B-3, containing both preS1- and preS2-derived proteins in addition to hepatitis B surface antigen, to circumvent their previous nonresponsiveness. The hepatitis B surface antigen antibody results from this group of patients show that 30 of the 86 individuals remained antibody non-responders and that 24 individuals (80%) expressed the HLA-DQB1*02 and that 21 individuals (70%) expressed HLA-DRB1*0701. Our results indicate that antibody nonresponse to the Hep B-3 vaccine is significantly associated with an extended HLA haplotype B44; DRB1*0701; DQB1*0202. A possible indication of these results is that antibody nonresponse to Hep B-3 vaccine is linked with the HLA allele DQB1*0202. These findings may have an important impact on future vaccine design.
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PMID:Contribution of human leukocyte antigens to the antibody response to hepatitis B vaccination. 924 49

Major histocompatibility complex (MHC) determinants control antibody production in response to protein antigens. Vaccination with hepatitis B surface antigen (HBsAg) frequently fails in hemodialyzed patients, but the genetic factors that modulate humoral responsiveness are poorly characterized. We studied the distribution of HLA class II alleles in 415 hemodialyzed Caucasian patients who received a full course of HBsAg vaccination, using class II oligotyping after genomic amplification of the DRB1 and DQB1 loci. Phenotype frequencies were compared in 114 non responders (anti-HBs antibodies < or = 10 SI units/liter), 301 responders (anti-HBs antibodies > 10 units/liter) and 471 healthy controls. DRB1*01 (DR1) and DRB1*15 (DR15) frequencies were lower in nonresponders than in responders and controls (DR1, 12.3% vs. 22.9% and 24.8%, respectively; DR15, 14% vs. 22.9% and 25.1%), while DRB1*03 (DR3) and DRB1*14 (DR14) frequencies were higher (DR3, 32.5% vs. 16.6% and 25.3%, respectively; DR14, 9.6% vs. 3% and 6.6%). Overall, 44.5% of DR3 or DR14 patients were nonresponders, compared to 18.1% of DR1 or DR15 patients (P = 0.0001). In conclusion the humoral response to HBsAg vaccine is influenced by class II allelic variants, which differ in their capacity to bind and present peptides to T lymphocytes.
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PMID:Distinct HLA class II alleles determine antibody response to vaccination with hepatitis B surface antigen. 960 93

We have studied the HLA-DRB and -DQB1 alleles of 42 paediatric patients who have suffered from membranous nephropathy associated with a hepatitis B infection (HBVMN). These patients were all from the Gdansk area of Northern Poland and the disease was diagnosed by light and electron microscopy. The control population consisted of 55 healthy children, approximately age matched, from schools in Gdansk. In addition we have also analysed 40 patients chronically infected with hepatitis B, without any renal involvement, as hepatitis B disease controls. The HLA alleles were defined using PCR/SSP. As idiopathic membranous nephropathy and low responsiveness to hepatitis B vaccine have been found to be associated with DR3 in Caucasoids, our hypothesis was that the HBVMN patients would show an increase in DR3. Our results indicate that, although there is a small increase in the frequency of DRBl*0301 in the HBVMN patients (16/42 38%) when compared to the healthy controls (15/55 31%), this does not approach significance. There is a significant increase in the frequency of DQB1*0303 in the HBVMN patients vs the healthy controls, after correction for the number of antigens detected (Pc)(13/42 vs 2/55, RR=11.6, P=0.0007, Pc=0.02). A similar increase in DQB1*0303 is seen in the HBVMN patients when compared to the hepatitis controls (13/42 vs 4/40) but this is only significant before correction (RR=4.3, P=0.04).
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PMID:HLA-DRB and -DQB1 alleles in Polish patients with hepatitis B associated membranous nephropathy. 975 1

Two HLA class II haplotypes, HLA-[DQB1*0602; DQA1*0102; DR15] and HLA-[DQB1*0603; DQA1*0103; DRB1*1301] were found to be less common in 52 nonresponders compared with 68 responders, P<0.025 and P<0.05 respectively, after vaccination with hepatitis B surface antigen (HBsAg). Another haplotype, HLA-[DQB1*0604; DQA1*0102; DRB1*1302], had a significantly higher frequency in the nonresponders (P<0.005). The nonresponders and responders were nonsmoking, healthy individuals with an antibody concentration of <10 IU/l and >100 IU/l respectively. The three haplotypes comprise either of three different DQB1*06 subtypes. Two of the seven amino acids that differ between the two responder alleles DQB1*0602 and *0603 and the nonresponder allele *0604 are located in the peptide-binding groove of the DQB1 molecule. In addition to this finding, amino acid 86 in the DRB1 molecule seems to determine the response against HBsAg. DRB1*1301 and DR15 in the responder haplotypes have a Val at this position while the nonresponder haplotype has a Gly. These results suggest a role for both the DQB1*06 alleles and the DRB1 alleles *1301, *1302 and DR15 to direct either a response or a nonresponse against HBsAg. Sixteen HLA class II genotypes were found to be shared by 25 nonresponders and 32 responders. This finding of HLA-identical nonresponders and responders indicates an influence of other genetic factors in addition to the HLA system in the response to HBsAg.
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PMID:Haplotypes comprising subtypes of the DQB1*06 allele direct the antibody response after immunisation with hepatitis B surface antigen. 982 Jun 1

Persistence of hepatitis B virus (HBV) infection is likely due to the interplay of the virus and host immune response. Given its critical role in antigen presentation, allelic differences in the HLA complex may affect HBV persistence. In a prospectively followed African American cohort, molecular class I and class II HLA typing was done on 31 subjects with persistent HBV infection and 60 controls who cleared the infection. HBV persistence was significantly associated with two class II alleles, DQA1 *0501 (odds ratio [OR], 2.6; P=.05) and DQB1 *0301 (OR, 3.9; P=.01), the two-locus haplotype consisting of these same two alleles (OR, 3; P=. 005) and the three-locus haplotype, DQA1 *0501, DQB1 *0301, and DRB1 *1102 (OR, 10.7; P=.01). In addition, HBV persistence was associated with class II allelic homozygosity. Several class I associations with persistence were also noted but were not statistically significant after correction for multiple comparisons. These results underscore the importance of the class II-mediated immune response in recovery from HBV infection.
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PMID:Class II HLA alleles and hepatitis B virus persistence in African Americans. 1006 98

We have shown that both demographic and immunogenetic factors are involved in the immune responses of Hepagene vaccinated individuals who were persistent nonresponders to 'S' containing hepatitis B vaccines. The HLA-DRB1 0701; DQB1 0202 genotype was found to be associated with a decline of anti-HBs antibodies (anti-HBs) and were frequent in those individuals who remained nonresponders following booster vaccination. Contrary to previously published 'S' vaccination data, Hepagene stimulated T-cell responses showed a lack of correlation with the humoral responses. Limiting dilution analysis demonstrated that the cellular immune response is associated with the kinetics of exposure to Hepagene rather than magnitude of the anti-HBs response. It remains that despite the inclusion of the pre-S proteins 74% nonresponder vaccinated individuals failed to produce > 100 IU/l of anti-HBs. However, these were persistent nonresponders and it was therefore encouraging that two doses of Hepagene did seroconvert (> 10 IU/L) 61% of this difficult group.
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PMID:The influence of host factors and immunogenetics on lymphocyte responses to Hepagene vaccination. 1019 68

From 1991 to 1998 we vaccinated 4835 neonates against hepatitis B virus (HBV) and monitored their humoral response to the recombinant vaccine. In a sample of 184 of these babies we studied the association between HLA class I and II genomic polymorphisms and humoral response to the vaccine and the association between the response and immune-mediated diseases. A subgroup of 96 babies also underwent HLA class III (C4A and C4B) typing. Four levels of humoral response were identified, each with a peculiar MHC restriction. Different HLA products seem to act as agonists (C4AQ0 and HLA-DQB1(*)02) or antagonists (C4AQ0, HLA-DQB1(*)02, and HLA-DRB1(*)11, DQB1(*)0301) in lowering humoral response to HBV vaccine. The group of responders was characterized more for lacking "nonresponder" alleles than for having specific "responder" ones. Tolerance to HBV peptides may have clinical implications, possibly being a marker for babies with a genetic risk of immunopathologies. In fact, many of the poor responders carried from two to four HLA-DQ alpha beta heterodimers predisposing to insulin-dependent diabetes mellitus and celiac disease. Two true nonresponders suffered from allergies and two slow responders had transient episodes of hyperglycemia.
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PMID:Humoral response to recombinant hepatitis B virus vaccine at birth: role of HLA and beyond. 1111 62

The G protein beta3 (GNB3) subunit and HLA are candidate genes predictive of immune response capacity. We therefore studied the influence of both gene systems on cellular and humoral immunity against hepatitis B virus (HBV) in 79 HBV booster-vaccinated healthy volunteers and an independent group of 77 probands after HBV basic immunization. Following booster vaccination, lymphocyte in vitro proliferation after stimulation with HBV surface antigen was 2.5-fold increased in GNB3 825T (TC + TT) vs CC allele carriers (P = 0.01) and was not influenced by HLA-DRB1 or DQB1 alleles. In addition, anti-HBs antibody titers in both groups were 2-fold increased in TC vs CC and decreased in TT vs CC allele carriers. However, antibody titers after HBV booster immunization were elevated in HLA-DQB1*0301 carriers (P corrected = 0.027). In summary, the GNB3 825T allele appears as a marker particularly predictive of cellular and HLA-DQB1*0301 of humoral immune responses following HBV vaccination.
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PMID:Role of G protein beta3 subunit C825T and HLA class II polymorphisms in the immune response after HBV vaccination. 1208 23

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


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