Dataset Information

CD3Z genetic polymorphism in immune response to hepatitis B vaccination in two independent Chinese populations.

ABSTRACT: Vaccination against hepatitis B virus is an effective and routine practice that can prevent infection. However, vaccine-induced immunity to hepatitis B varies among individuals. CD4(+) T helper cells, which play an important role in both cellular and humoral immunity, are involved in the immune response elicited by vaccination. Polymorphisms in the genes involved in stimulating the activation and proliferation of CD4(+) T helper cells may influence the immune response to hepatitis B vaccination. In the first stage of the present study, a total of 111 single nucleotide polymorphisms (SNPs) in 17 genes were analyzed, using the iPLEX MassARRAY system, among 214 high responders and 107 low responders to hepatitis B vaccination. Three SNPs (rs12133337 and rs10918706 in CD3Z, rs10912564 in OX40L) were associated significantly with the immune response to hepatitis B vaccination (P?=?0.008, 0.041, and 0.019, respectively). The three SNPs were analyzed further with the TaqMan-MGB or TaqMan-BHQ probe-based real-time polymerase chain reaction in another independent population, which included 1090 high responders and 636 low responders. The minor allele 'C' of rs12133337 continued to show an association with a lower response to hepatitis B vaccination (P?=?0.033, odds radio?=?1.28, 95% confidence interval?=?1.01-1.61). Furthermore, in the stratified analysis for both the first and second populations, the association of the minor allele 'C' of rs12133337 with a lower response to hepatitis B vaccination was more prominent after individuals who were overweight or obese (body mass index ?25 kg/m(2)) were excluded (1(st) stage: P?=?0.003, 2(nd) stage: P?=?0.002, P-combined?=?9.47e-5). These findings suggest that the rs12133337 polymorphism in the CD3Z gene might affect the immune response to hepatitis B vaccination, and that a lower BMI might increase the contribution of the polymorphism to immunity to hepatitis B vaccination.

SUBMITTER: Pan LP

PROVIDER: S-EPMC3329423 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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CD3Z genetic polymorphism in immune response to hepatitis B vaccination in two independent Chinese populations.

Pan Li-Ping LP Zhang Wei W Zhang Li L Wu Xiao-Pan XP Zhu Xi-Lin XL Yan Bing-Yu BY Li Jing-Yun JY Xu Ai-Qiang AQ Liu Ying Y Li Hui H

PloS one 20120418 4

Vaccination against hepatitis B virus is an effective and routine practice that can prevent infection. However, vaccine-induced immunity to hepatitis B varies among individuals. CD4(+) T helper cells, which play an important role in both cellular and humoral immunity, are involved in the immune response elicited by vaccination. Polymorphisms in the genes involved in stimulating the activation and proliferation of CD4(+) T helper cells may influence the immune response to hepatitis B vaccination. ...[more]

PMID: 22536368

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Project description:Many current vaccines are less immunogenic and less effective in elderly compared to younger adults due to age-related changes of the immune system. Most vaccines utilized in the elderly contain antigens, which the target population has had previous contact with due to previous vaccination or infection. Therefore, most studies investigating vaccine-induced immune responses in the elderly do not analyze responses to neo-antigens but rather booster responses. However, age-related differences in the immune response could differentially affect primary versus recall responses. We therefore investigated the impact of age on primary and recall antibody responses following hepatitis B vaccination in young and older adults. Focused gene expression profiling was performed before and 1 day after the vaccination in order to identify gene signatures predicting antibody responses. Young (20-40?years; n?=?24) and elderly (>60?years; n?=?17) healthy volunteers received either a primary series (no prior vaccination) or a single booster shot (documented primary vaccination more than 10?years ago). Antibody titers were determined at days 0, 7, and 28, as well as 6?months after the vaccination. After primary vaccination, antibody responses were lower and delayed in the elderly compared to young adults. Non-responders after the three-dose primary series were only observed in the elderly group. Maximum antibody concentrations after booster vaccination were similar in both age groups. Focused gene expression profiling identified 29 transcripts that correlated with age at baseline and clustered in a network centered around type I interferons and pro-inflammatory cytokines. In addition, smaller 8- and 6-gene signatures were identified at baseline that associated with vaccine responsiveness during primary and booster vaccination, respectively. When evaluating the kinetic changes in gene expression profiles before and after primary vaccination, a 33-gene signature, dominated by IFN-signaling, pro-inflammatory cytokines, inflammasome components, and immune cell subset markers, was uncovered that was associated with vaccine responsiveness. By contrast, no such transcripts were identified during booster vaccination. Our results document that primary differs from booster vaccination in old age, in regard to antibody responses as well as at the level of gene signatures. Clinical Trial Registration:www.clinicaltrialsregister.eu, this trial was registered at the EU Clinical Trial Register (EU-CTR) with the EUDRACT-Nr. 2013-002589-38.

Dataset Information

CD3Z genetic polymorphism in immune response to hepatitis B vaccination in two independent Chinese populations.

Publications

CD3Z genetic polymorphism in immune response to hepatitis B vaccination in two independent Chinese populations.

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