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

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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: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.

Project description:Increasing evidences suggest that HBsAg-production varies across HBV-genotypes. HBsAg C-terminus plays a crucial role for HBsAg-secretion. Here, we evaluate HBsAg-levels in different HBV-genotypes in HBeAg-negative chronic infection, the correlation of specific mutations in HBsAg C-terminus with HBsAg-levels in-vivo, their impact on HBsAg-secretion in-vitro and on structural stability in-silico.HBsAg-levels were investigated in 323 drug-naïve HBeAg-negative patients chronically infected with HBV genotype-D(N = 228), -A(N = 65) and -E(N = 30). Genotype-D was characterized by HBsAg-levels lower than genotype-A and -E (3.3[2.7-3.8]IU/ml; 3.8[3.5-4.2]IU/ml and 3.9[3.7-4.2]IU/ml, P < 0.001). Results confirmed by multivariable analysis correcting for patients'demographics, HBV-DNA, ALT and infection-status.In genotype-D, specific C-terminus mutations (V190A-S204N-Y206C-Y206F-S210N) significantly correlate with HBsAg<1000IU/ml(P-value from <0.001 to 0.04). These mutations lie in divergent pathways involving other HBsAg C-terminus mutations: V190A + F220L (Phi = 0.41, P = 0.003), S204N + L205P (Phi = 0.36, P = 0.005), Y206F + S210R (Phi = 0.47, P < 0.001) and S210N + F220L (Phi = 0.40, P = 0.006). Notably, patients with these mutational pairs present HBsAg-levels 1log lower than patients without them(P-value from 0.003 to 0.02). In-vitro, the above-mentioned mutational pairs determined a significant decrease in HBsAg secretion-efficiency compared to wt(P-value from <0.001 to 0.02). Structurally, these mutational pairs reduced HBsAg C-terminus stability and determined a rearrangement of this domain.In conclusion, HBsAg-levels in genotype-D are significantly lower than in genotype-A and -E in HBeAg-negative patients. In genotype-D, specific mutational clusters in HBsAg C-terminus correlate with lower HBsAg-levels in-vivo, hamper HBsAg-release in-vitro and affect its structural stability, supporting their detrimental role on HBsAg-secretion. In this light, genotypic-testing can be a valuable tool to optimize the clinical interpretation of HBsAg in genotype-D and to provide information on HBV-pathogenicity and disease-progression.

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.

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.

Similar Datasets

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