Dataset Information

Association of IL-10 and IL-10RA single nucleotide polymorphisms with the responsiveness to HBV vaccination in Chinese infants of HBsAg(+)/HBeAg(-) mothers: a nested case-control study.

ABSTRACT:

Objectives

To investigate the association of interleukin (IL)-10 and IL-10 receptor A (IL-10RA) single nucleotide polymorphisms with the responsiveness to hepatitis B virus (HBV) vaccination in newborns whose mothers were hepatitis B surface antigen (HBsAg)(+)/hepatitis B e antigen (HBeAg)(-).

Design

Nested case-control study.

Setting

Changchun, China.

Participants

713 infants from a Han Chinese population whose mothers were HBsAg(+)/HBeAg(-) and participated in the prevention of mother-to-child transmission of HBV at the First Hospital of Jilin University from July 2012 to July 2015 were included. Infants were excluded for HBsAg-positive; unstandardised vaccination process; inadequate blood samples; not Han Chinese and failed genotyping.

Results

Infants with artificial feeding pattern were correlated with low responsiveness to HBV vaccination (p=0.009). The GG genotype of IL-10 rs3021094 was correlated with a higher risk of low responsiveness to HBV vaccination (OR 2.80, 95% CI 1.35 to 5.83). No haplotype was found to be correlated with responsiveness to HBV vaccination. No gene-gene interaction was found between IL-10 and IL-10RA.

Conclusions

Our study found that IL-10 gene variants were significantly associated with the immune response to the HBV vaccine. Identifying these high-risk infants who born to HBsAg(+)/HBeAg(-) mothers and low responses to hepatitis B vaccination will provide evidence for individualised prevention strategies.

SUBMITTER: Wen S

PROVIDER: S-EPMC6278805 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of IL-10 and IL-10RA single nucleotide polymorphisms with the responsiveness to HBV vaccination in Chinese infants of HBsAg(+)/HBeAg(-) mothers: a nested case-control study.

Wen Simin S Wu Yanhua Y Pan Yuchen Y Cao Mengzhuo M Zhao Dan D Wang Chong C Wang Chuan C Kong Fei F Li Jie J Niu Junqi J Jiang Jing J

BMJ open 20181128 11

<h4>Objectives</h4>To investigate the association of interleukin (IL)-10 and IL-10 receptor A (IL-10RA) single nucleotide polymorphisms with the responsiveness to hepatitis B virus (HBV) vaccination in newborns whose mothers were hepatitis B surface antigen (HBsAg)(+)/hepatitis B e antigen (HBeAg)(-).<h4>Design</h4>Nested case-control study.<h4>Setting</h4>Changchun, China.<h4>Participants</h4>713 infants from a Han Chinese population whose mothers were HBsAg(+)/HBeAg(-) and participated in the ...[more]

PMID: 30498038

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Project description:BackgroundAlthough hepatitis B vaccination has a significant impact on the reduction hepatitis B virus (HBV) infection, babies born to hepatitis B surface antigen (HBsAg) positive mothers bear a high risk of being poor responsive to the vaccine with unilluminated mechanism. Toll-like receptor 3 (TLR3) plays a vital role in placental immunity, which affects the immune response of these babies. This study investigated the role of placental TLR3 in the immune responses of babies born to HBsAg-positive mothers to the HBV vaccine.MethodsOne hundred pairs of HBsAg-positive mothers and their newborns were recruited. Maternal blood samples were collected before delivery, and placental tissues were collected after delivery. Newborns were administered standard passive and active immunoprophylaxis and followed up until the age of 1. Infant blood samples were collected at 1 year of age. Mothers and infants were tested for HBV serological markers and HBV DNA by electrochemiluminescence immunoassay and fluorescence quantitative polymerase chain reaction. respectively. Placental TLR3 was detected by immunohistochemistry and score in a semi-quantitative fashion, circulating cytokines in infants were detected by enzyme-linked immunosorbent assay. Infants with anti-HBs ≥100 and <100 mIU/mL were classified into the high-responsiveness group and the non- or hypo-responsiveness group.ResultsThe TLR3 protein was expressed in all placentas. Compared with the high-responsiveness group, the expression of TLR3 in the non- or hypo-responsiveness group was significantly decreased (χ2=10.39, P=0.001). A non-conditional logistic regression model showed that the increased expression of placental TLR3 protein decreased the odds of HBV vaccine non- or hypo-responsiveness in the babies of HBsAg-positive mothers [OR =0.25 (95% CI: 0.11-0.58)], and this association remained significant after accounting for maternal factors, such as HBeAg and HBV DNA, as well as infant cytokines, including IL-6, IL-12, TNF-α, IFN-α, and IFN-γ [OR =0.15 (95% CI: 0.05-0.44)].ConclusionsDecreased placental TLR3 expression is associated with impaired responsiveness to HBV vaccination in babies born to HBsAg-positive mothers.

Project description:Background & aimCytotoxic T-lymphocyte-associated protein 4 (CTLA-4) attenuates cytotoxic T lymphocyte (CTL) activation. This study was performed to examine the relationships between CTLA-4 genotypes/haplotypes, hepatitis B surface antigen (HBsAg), and hepatitis B core-related antigen (HBcrAg) levels, and their potential impact on the clinical course of chronic HBV infection.MethodsWe recruited 145 treatment-naïve patients with genotype B or C chronic HBV infection who were initially hepatitis B e-antigen (HBeAg)-positive and had been followed from a mean age of 7.08 years for a total of 4,787 person-years in the study cohort. We also recruited another 69 treatment-naïve adults with genotype B or C chronic HBV infection as a validation cohort. We assessed the CTLA-4 gene single nucleotide polymorphisms rs4553808 (-A1661G)/rs5742909 (-C318T) in both cohorts, and the serum HBsAg and HBcrAg levels in the study cohort.ResultsCTLA-4 promoter haplotypes were associated with HBsAg and HBcrAg levels at 10 and 15 years of age in the study cohort. Patients with the CTLA-4 AA/CC haplotype showed earlier spontaneous HBeAg seroconversion (hazard ratio = 1.58; p = 0.02), and a more rapid annual decline in the serum HBsAg level than other patients (0.09 vs. 0.03 log10 IU/ml/year, p = 0.02). The CTLA-4 AA/CC haplotype was also predictive of HBeAg seroconversion in the validation cohort (p = 0.01).ConclusionsChronic HBV-infected patients with a CTLA-4 AA/CC haplotype had lower serum HBsAg and HBcrAg levels in childhood and earlier spontaneous HBeAg seroconversion.Impact and implicationsThe role of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in chronic HBV-infected children has not been studied previously. In a very long-term cohort followed from childhood to adulthood, we showed that CTLA-4 haplotypes are associated with HBV biomarker levels in childhood and are correlated with the clinical course of chronic HBV infection. CTLA-4 pathway may serve as a future target for the development of therapeutic agents against HBV infection.

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Dataset Information

Association of IL-10 and IL-10RA single nucleotide polymorphisms with the responsiveness to HBV vaccination in Chinese infants of HBsAg(+)/HBeAg(-) mothers: a nested case-control study.

Objectives

Design

Setting

Participants

Results

Conclusions

Publications

Association of IL-10 and IL-10RA single nucleotide polymorphisms with the responsiveness to HBV vaccination in Chinese infants of HBsAg(+)/HBeAg(-) mothers: a nested case-control study.

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