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 have recently shown that the human antibody response to the hepatitis B virus surface antigen (HBsAg) vaccine is major histocompatibility complex (MHC) associated. In studies of nonresponders to the vaccine, we found an increased incidence of individuals homozygous for human histocompatibility leukocyte antigen (HLA) proteins associated with the extended (conserved) haplotype [HLA-B8,SC01,DR3]. In later prospective vaccination trials, we showed that none of five individuals homozygous for this haplotype developed more than 1,300 radioimmunoassay (RIA) units of antibody (mean, 467 RIA units), while all heterozygotes made at least 2,500 RIA units (mean antibody level, 15,608 units). Our results suggested that [HLA-B8,SC01,DR3] lacks an immune response gene for HBsAg, and that response is inherited in a dominant fashion. To provide further evidence for this hypothesis, we have now analyzed the results of HBsAg immunization in families. 43 members of 10 families were immunized with the hepatitis B vaccine, including seven families where at least one member bore the haplotype [HLA-B8,SC01,DR3], and three families where one member had already received, but failed to respond to, the vaccine. In two of these three families, the presence of [HLA-B8,SC01,DR3] was subsequently found. Of nine MHC-identical sibling pairs in the study, both members of eight pairs had similar antibody responses (five nonresponder and three responder pairs). In all families with such sibling pairs, including the discordant pair, rank-ordering members by antibody level demonstrated that no relative's value came between the sibling pair values. Furthermore, of nine [HLA-B8,SC01,DR3]-haplotype-homozygous individuals, six were nonresponders, and two others had only low-normal responses. [HLA-B8,SC01,DR3]-heterozygous family members always had higher levels of antibody than their homozygous relatives. Linkage analysis of nonresponse to HLA haplotypes revealed a maximum likelihood LOD (logarithm of the odds) score of 6.3 at a recombination fraction of 0.1. The MHC association with lack of antibody response to HBsAg was not seen with tetanus immunization, where 1 of 20 HBsAg responders and 1 of 21 poor or nonresponders had tetanus titers of less than 1:512; both tetanus nonresponders were [HLA-B8,SC01,DR3] heterozygotes. Our results indicate that: (a) response to the HBsAg vaccine is MHC linked, and inherited in a dominant fashion; (b) an abnormal or missing immune response (Ir) gene for HBsAg is a characteristic of most examples of the extended haplotype [HLA-B8,SC01,DR3]; and (c) other haplotypes also have abnormal or missing Ir genes for HBsAg.
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PMID:The immune response to hepatitis B vaccine in humans: inheritance patterns in families. 153 Oct 63

Lymphoblastoid interferon is effective therapy in some but not all patients with chronic hepatitis B virus infection. To assess whether immunological parameters were predictive of response to interferon therapy, we determined the human leukocyte antigen type, CD4/CD8 ratio, natural killer cell activity, IgM anti-HBc antibody levels and concanavalin A-induced lymphocyte proliferative response in 30 patients before treatment. In addition, to investigate the mechanisms of action of interferon in promoting hepatitis B virus clearance, we serially measured the CD4/CD8 ratios, natural killer activity and lymphocyte proliferative response at wk 4, 8 and 12 of treatment. A beneficial response to therapy was defined as the sustained clearance of HBeAg and serum hepatitis B virus DNA within 1 yr of commencing therapy. Elevated IgM anti-HBc levels were associated with a beneficial response to therapy, but there was no correlation observed between response and pretreatment CD4/CD8 ratio, natural killer activity or lymphocyte proliferative response. Six of seven human leukocyte antigen DR3-positive patients responded. No measurable changes in the immunological parameters studied were observed in the nonresponder group, whereas a significant rise in CD4/CD8 ratio, associated with a fall in peripheral CD8 number and a decline in measurable NK activity, was seen in the responder group. These changes were maximal at the time of hepatitis B virus DNA clearance, which was associated with a transient increase in hepatic inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunological studies before and during interferon therapy in chronic HBV infection: identification of factors predicting response. 169 61

We had previously obtained evidence that among normal subjects the humoral antibody response to hepatitis B surface antigen (HBsAg) was bimodally distributed with about 14% of subjects producing less than 1,000 estimated radioimmunoassay RIA units. From the study of major histocompatibility complex (MHC) markers in the very poor responders who produced less than 36 estimated RIA units of antibody, it appeared that there was an excess of homozygotes for two extended haplotypes [HLA-B8, SC01, DR3] and [HLA-B44, FC31, DR7]. This finding suggested that a poor response was inherited as a recessive trait requiring nonresponse genes for HBsAg on both MHC haplotypes and was strengthened by finding a much lower antibody response among prospectively immunized homozygotes for [HLA-B8, SC01, DR3] compared with heterozygotes. In the present study, we have analyzed the cellular basis for nonresponse to this antigen by examining antigen-specific proliferation of T cells from responders and nonresponders in the presence and absence of autologous CD8+ (suppressor) cells. Peripheral blood cells from nonresponders to HBsAg failed to undergo a proliferative response to recombinant HBsAg in vitro, whereas cells from responders proliferated vigorously. This failure of cells from nonresponders to proliferate was not reversed in cell mixtures containing CD4+ and antigen-presenting cells devoid of CD8+ cells. There was no difference between responders and nonresponders with respect to the number of circulating T cells or their subsets, or the proliferative response to mitogens such as pokeweed or phytohemagglutinin or another antigen, tetanus toxoid. Our results indicate that our HBsAg nonresponding subjects have a very specific failure in antigen presentation or the stimulation of T helper cells, or both. Our evidence is against specific immune suppression as the basis for their nonresponsiveness. The failure of antigen presentation or T cell help is consistent with recessive inheritance of nonresponsiveness and suggests that response is dominantly inherited.
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PMID:The cellular basis for lack of antibody response to hepatitis B vaccine in humans. 182 4

Genetic factors are implicated in the response of normal subjects to hepatitis B vaccine. The aim of our study was to investigate if HLA Class I and II proteins could participate in a nonresponse to this vaccine in immunocompromised, namely hemodialyzed, patients. One hundred and seven hemodialyzed patients (68 men and 39 women, mean age 35 years) were vaccinated with Pasteur Hevac B vaccine, with a mean delay of 2 months following the onset of chronic hemodialysis. Patients were considered nonresponders when their serum antiHBs remained less than 10 mUI/ml on at least two occasions within the 12 months following the vaccination. HLA-A, B and DR antigens were determined by complement-dependent microlymphotoxicity. Ninety patients (84%) were responders and 17 (16%) nonresponders. The HLA-A1, B8 and DR3 frequency was higher in nonresponders (35, 35 and 44%, respectively) than in responders (18, 4 and 14%, respectively). The extended haplotype HLA-A1, B8, DR3 was more frequent in the former (19%) than in the latter (2%) (p less than 0.03). There was only one female within the nonresponders (6%) as compared to 37 (41%) in the responders (p less than 0.05). We conclude that genetic determinants (sex and HLA markers) play a critical role in the induction of an antiHBs immune response in both immunoincompetent hemodialyzed patients and normal immunocompetent hosts.
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PMID:Genetic basis of nonresponse to hepatitis B vaccine in hemodialyzed patients. 229 31

In order to detect a possible HLA linked genetic control of human immune responses to hepatitis B virus, forty healthy adult persons of the same age typed for HLA-A, -B and -DR antigens, were vaccinated against virus hepatitis B and sequentially tested for anti-HBs and anti-pre-S2 antibodies. They received three injections of Hevac-B Pasteur vaccine, the second 1 month and the third 3 months after the first. Following the third immunization, 38 individuals (95%) had a protective level of anti-HBs antibodies and 17 (42.3%) had a positive level of anti-pre-S2 antibodies. HLA-A11 antigen was significantly more frequent (pc = 0.007) among anti-HBs high responders than low responders. In addition, anti-HBs high responders were more frequently HLA-DR1, and less frequently HLA-DR4 and DR7 positive; corrected values, however, were not significant. Anti-pre-S2 high responders showed an apparent increase of HLA-B7, B14 or DR3 antigens, when compared to low responders (pc not significant).
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PMID:HLA linked immune response to S and pre-S2 gene products in hepatitis B vaccination. 247 13

In previous studies of the antibody response to hepatitis B vaccine in 598 subjects who received a full course of vaccination, we observed a bimodal response, with about 14 percent producing less than approximately 1000 radioimmunoassay (RIA) units. An analysis of the major histocompatibility complex (MHC) HLA and complement types of 20 of the subjects with the lowest responses indicated a greater-than-expected number of homozygotes for the extended or fixed MHC haplotype [HLA-B8, SC01, DR3]. This finding suggested that the lack of a normal response was a recessive MHC-linked trait. In this study, we prospectively vaccinated five homozygotes and nine heterozygotes for this haplotype in the expectation that the homozygotes would produce much lower levels of antibody than the heterozygotes. When the antibody response was assessed two months after the third injection, four of the five homozygotes had produced very low levels (approximately 1000 units or less) of antibody (mean, 467 RIA units; range, less than 8 to 1266), whereas all nine heterozygotes produced more than 2500 RIA units (mean, 15,608; range, 2655 to 28,900) (P less than 0.01). We conclude that the usual response to hepatitis B surface antigen is due to the presence of a dominant immune-response gene in the MHC and that a low response is due to the absence of such a gene and the presence on both chromosomes of MHC haplotypes (such as [HLA-B8, SC01, DR3]) that indicate such a response.
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PMID:Genetic prediction of nonresponse to hepatitis B vaccine. 213 97

Twenty-eight health care workers who had a poor antibody response when initially vaccinated with hepatitis B vaccine were revaccinated with three additional 20-microgram doses. Eight of the twenty nonresponders, who had levels of antibody to hepatitis B surface antigen (anti-HBs) of less than 8 estimated radioimmunoassay (RIA) units, and all 8 of the hyporesponders, who had anti-HBs levels of 8 or 16 RIA units, attained anti-HBs levels of 36 RIA units or more after revaccination. Tests for HLA-A, B, C, and DR; for complement proteins C2, C4A, C4B, and BF; and for the erythrocyte enzyme glyoxalase I were done in 17 nonresponders and 3 hyporesponders. Nine (45%) had HLA-DR7 and 8 (40%) had HLA-DR3, compared with an expected rate of 23% in the general population. At least one of two extended haplotypes (B44, DR7, FC31 or B8, DR3, SCO1) were detected in 6 of the 9 who did not respond to revaccination, compared with 2 of 11 who responded to a second course of vaccine. Poor responders to vaccine may benefit from revaccination, and genetic factors may modulate the immune response to vaccination.
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PMID:Nonresponsiveness to hepatitis B vaccine in health care workers. Results of revaccination and genetic typings. 294 2

Yeast recombinant hepatitis B vaccine was administered to 25 nonresponders to the plasma-derived hepatitis B vaccine. After three 10-micrograms doses, nine subjects (36%) produced levels of antibodies to hepatitis B surface antigen (anti-HBs) of less than 2.1 sample ratio units (SRU) (nonresponders), and five (20%) developed anti-HBs of 2.1 to 9.9 SRU (hyporesponders); anti-HBs levels of 10 SRU or greater were detected at least once in 11 vaccinees (44%), but by the sixth and 12th months after the last vaccination, only three and one of these "responders," respectively, still maintained anti-HBs values of 10 SRU or greater. In these 25 subjects HLA subtyping showed a high prevalence of DR7, B8, and the combinations of DR3 and DR7 and DR4 and DR7. Our findings indicate that the yeast recombinant hepatitis B vaccine was not effective in eliciting a sustained anti-HBs response in nonresponders to the plasma hepatitis B vaccine.
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PMID:Lack of response to recombinant hepatitis B vaccine in nonresponders to the plasma vaccine. 252 37

To study the immunoreactivity genes in a heterogeneous human population needs a large number of individuals. Associations between HLA antigens and immunoresponse to viral or bacterial antigens have been studied with controversial results. As a homogeneous population, the MHC class I, II and III allele distribution was studied in 153 end-stage renal disease patients (ESRD, average duration of renal replacement: 8.2 + 5.1 years) immunized with a recombinant hepatitis B vaccine in accordance to the standard vaccination schedule. Thirty-four patients with an antibody titre of less than 10 U/l following the last booster injection were considered as non-responders while 119 patients with antibody titre equal to or more than 10 U/l were considered as responders. The responder group was divided into two subgroups: low responders (antibody titre: < or = 1000 U/l) and high responders (antibody titre: > 1000 U/1). Marked differences were observed between responders and non-responders in the occurrence of carriers of different MHC class I, II and III alleles. Homozygotes for HLA-A1, HLA-B8, HLA-DR3 and HLA-DQ2 were found almost exclusively in the non-responder group and significantly more heterozygotes for these alleles were found in the non-responder group compared to the responders. Similar albeit less marked differences were found in the frequency of some MHC class III alleles (C4A*6, C4A*QO, Bf*F, Bf*S0.7). Within the responder group, carriers of HLA-A2, HLA-B7 and HLA-DR4 were found to be clustered in the low responder sub-group whereas carriers of HLA-A1, HLA-B27, HLA-Cw2, C4A*6 and Bf*F were observed more frequently in the group of high responders. Similar differences were found with extended haplotypes as well. For example, the extended haplotypes HLA-A1, B8, BfS, C4AQO, C4B1, DR3, DQ2 and HLA-A1, B8, BfF, C4A6, C4B2, DR3, DQ2 were present in nine of 34 cases of non-responders but only in one of 119 case of responders (P < 0.000001). These observations indicate that the presence or absence of certain MHC alleles even in heterozygous form determine the responsiveness to hepatitis B vaccination in end-stage renal disease patients, and among responders, the intensity of antibody response is also markedly influence by immunogenetic factors.
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PMID:Relationship between the reactivity to hepatitis B virus vaccination and the frequency of MHC class I, II and III alleles in haemodialysis patients. 763 Nov 46

The study was undertaken to evaluate the relationship between non-responsiveness to hepatitis B (HBV) vaccination in haemodialysed patients and HBs antigen (Ag) presentation and recognition depending on TCR/CD3 receptors expression. We have found that the cause of the blunted response to HBV vaccination is multifactorial and seems to be associated with the following: (1) A reduced number of TCR/CD3 antigen receptor complexes on freshly isolated uraemic CD4 T cells, especially in non-responders. (2) The blunted proliferative response of uraemic CD4 T cells isolated from non-responders and stimulated for 6 days by autologous monocytes presenting HBsAg was associated with the decreased density of the TCR/CD3 receptors. (3) Moreover, in uraemic non-responders the expression of adhesion and accessory molecules on monocytes (intercellular adhesion molecule-1/ICAM-1, HLA-DR/Ia/) was significantly decreased following the culture with autologous monocytes serving as HBsAg-presenting cells. CD4 molecules and lymphocyte function antigen-1 beta/LFA-1 beta/ on helper-inducer T cells were increased before and after the culture. (4) These findings were also associated with a diminished binding capacity of IL-1 beta and IL-6 to their receptors on helper-inducer T cells. (5) IL-2, IFN-gamma and IL-4 production was decreased in uraemic non-responders, especially after 72 h of the culture. (6) Inhibited proliferation of helper-inducer T cells in uraemic non-responders was only partially reversible in the presence of exogenous IL-1 beta, IL-6, IL-2 and IFN-gamma. (7) HLA typing of uraemic non-responders was associated with extended haplotype: HLA A1,B8,DR3,DR7,DQ2.
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PMID:Non-responsiveness to hepatitis B vaccination in haemodialysis patients: association with impaired TCR/CD3 antigen receptor expression regulating co-stimulatory processes in antigen presentation and recognition. 791 Jun 75


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