Relationship between the HBsAg-positive infection status of mothers and the non/low-response to hepatitis B vaccine of their infants / 中华流行病学杂志

Objective: To explore the relationship between the status of HBsAg-positive infection of mothers and the non/low-response to hepatitis B vaccine of their infants. Methods: A total of 225 pairs of mothers and their infants were recruited in our cohort from June 2011 to July 2013. Infants were given three doses of hepatitis B vaccine at hour 24, first month and month 6(t)h respectively and were followed up for one year after birth. HBV serological markers and HBV DNA in the peripheral blood of both mothers and infants were detected by Electro-chemiluminescence immunoassay and fluorescence quantitative Polymerase Chain Reaction. Results: Six HBV infection models were detected in HBsAg-positive mothers, and "HBsAg (+), HBeAg (+), anti-HBc (+)" (model one) and "HBsAg (+), anti-HBe (+), anti-HBc (+)" (model two) accounted for 92.5%(208/225) of all the models. Rate of non/low-response to hepatitis B vaccine in infants born to mothers in model one was lower than those in model two, the differences are statistically significant (χ(2)=4.80, P=0.029). The rate of non/low-response to hepatitis B vaccine in infants showed a downward trend with the rising of HBeAg level in their mothers (χ(2)=4.86, P=0.028). Results from the unconditional logistic regression analysis showed that the HBeAg of the HBsAg-positive mothers was significantly correlated with the low risk of non/low-response to hepatitis B vaccine in infants (OR=0.598, 95%CI: 0.378-0.947). The positive rate of serum HBV DNA in HBsAg-positive mothers was 54.2%, while the rate of non/low-response to hepatitis B vaccine in infants born to HBV DNA positive mothers was similar to those infants born to HBV DNA negative mothers (χ(2)=0.22, P=0.640). Conclusions: "HBsAg (+), HBeAg (+), anti-HBc (+)" and "HBsAg (+), anti-HBe(+), anti-HBc (+)" were the common models seen in HBsAg-positive mothers, and the rate of non/low-response to hepatitis B vaccine was different between the two models. HBeAg of HBsAg-positive mothers might have positive effects on the immune response to hepatitis B vaccine in infants but the mechanisms remained not clear. HBV DNA of the HBsAg-positive mothers did not seem to be correlated with the immune response to hepatitis B vaccine in infants.

Relationship between the HBsAg-positive infection status of mothers and the non/low-response to hepatitis B vaccine of their infants / 中华流行病学杂志

Objective To explore the relationship between the status of HBsAg-positive infection of mothers and the non/low-response to hepatitis B vaccine of their infants.Methods A total of 225 pairs of mothers and their infants were recruited in our cohort from June 2011 to July 2013.Infants were given three doses of hepatitis B vaccine at hour 24,first month and month 6th respectively and were followed up for one year after birth.HBV serological markers and HBV DNA in the peripheral blood of both mothers and infants were detected by Electro-chemiluminescence immunoassay and fluorescence quantitative Polymerase Chain Reaction.Results Six HBV infection models were detected in HBsAg-positive mothers,and "HBsAg (+),HBeAg (+),anti-HBc (+)" (model one) and "HBsAg (+),anti-HBe (+),anti-HBc (+)" (model two) accounted for 92.5％ (208/225) of all the models.Rate of non/low-response to hepatitis B vaccine in infants born to mothers in model one was lower than those in model two,the differences are statistically significant (x2=4.80,P=0.029).The rate of non/low-response to hepatitis B vaccine in infants showed a downward trend with the rising of HBeAg level in their mothers (x2=4.86,P=0.028).Results from the unconditional logistic regression analysis showed that the HBeAg of the HBsAg-positive mothers was significantly correlated with the low risk of non/low-response to hepatitis B vaccine in infants (OR=0.598,95％CI:0.378-0.947).The positive rate of serum HBV DNA in HBsAg-positive mothers was 54.2％,while the rate of non/low-response to hepatitis B vaccine in infants born to HBV DNA positive mothers was similar to those infants born to HBV DNA negative mothers (X2=0.22,P=0.640).Conclusions "HBsAg (+),HBeAg (+),anti-HBc (+)" and "HBsAg (+),anti-HBe(+),anti-HBc (+)" were the common models seen in HBsAg-positive mothers,and the rate of non/low-response to hepatitis B vaccine was different between the two models.HBeAg of HBsAg-positive mothers might have positive effects on the immune response to hepatitis B vaccine in infants but the mechanisms remained not clear.HBV DNA of the HBsAg-positive mothers did not seem to be correlated with the immune response to hepatitis B vaccine in infants.

Influencing factors for non/low-response to hepatitis-B vaccine in infants of HBsAg positive mothers / 中华流行病学杂志

Objective To investigate the influencing factors for non/low-response to hepatitis B vaccine in infants of HBsAg-positive mothers.Methods A total of 286 HBsAg-positive pregnant women and their infants were recruited from the Third People's Hospital of Taiyuan during July 2011 to January 2013.The infants were immunized with hepatitis B vaccine according to the 0-1-6 month vaccination schedule and followed up for 12 months.The serum HBV DNA level of mothers,neonates and infants were detected by electro chemilum inescence immunoassay kits and fluorescene quantiative polymerase chain rection.Results Among 286 infants,the rate of non/low-response to hepatitis B vaccine was 18.53％ (53/286).Non-conditional logistic regression analysis indicated that the mother's HBV DNA level ≥ 1 × 107 copies/ml (0R=2.592,95％CI:1.121-5.996) and natural birth (OR=1.932,95％CI:1.021-3.654) were the risk factors for non/low-response to hepatitis B vaccine,the risks were 2.592 times and 1.932 times higher compared with the infants whose mothers were HBV DNA negative and the infants whose mothers had cesarean delivery.There was no multiplicative or additive interaction between high HBV DNA load and natural birth (OR=1.055,95％CI:0.209-5.321),(RERI=1.617,95％CI:-4.038-7.272;AP=0.364,95％CI:-).527-1.225;SI=1.195,95％CI:0.270-13.135).After stratified analysis of mother's HBV DNA level,delivery mode of mothers was not associated with non/low-response of their infants.Conclusion The mother's load of HBV DNA ≥ 1 × 107 copies/ml might be the factor for non/low-response to hepatitis B vaccine in infants of HBsAg positive mothers.

Effect of interleukin-6 and interleukin-12 on immune response to hepatitis B vaccination in infants of HBsAg-positive mothers / 中华流行病学杂志

Objective To explore the effect of interleukin-6 (IL-6) and Interleukin-12(IL-12) on immune response to hepatitis B vaccination in infants of HBsAg-positive mothers.Methods A total of 91 neonates whose mothers were HBsAg-positive were included and followed up for 12 months.HBV DNA and HBV serological markers in the peripheral blood of the neonates and infants were detected with fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescence immunoassay (CLIA),and the levels of IL-6 and IL-12 in the peripheral blood of the neonates and infants were detected with enzyme-linked immunosorbent assay (ELISA).Results The non-/hypo-response rate to hepatitis B vaccination was 35.16％ (32/91) in the 91 infants.In the neonatal period and infantile period,the level of IL-6 in non-/hypo-response group was lower than that in high-response group,while the level of IL-12 was higher than that in high-response group,and there was significant difference (P＜0.01).From the neonatal period to the infantile period,the level of IL-6 increased,while the level of IL-12 descended in both groups,and there was significant difference (P＜0.01).Furthermore,the level of anti-HBs of infants was positively correlated with the level of IL-6 (rs =0.70,0.79,P＜ 0.01),and was negatively correlated with the level of IL-12 (rs=-0.71,-0.72,P＜0.01) in the neonatal period and the infantile period.From the neonatal period to the infantile period,the increased level of IL-6 was positively associated with the level of anti-HBs (rs =-0.74,P＜0.01),while the decreased level of IL-12 was negatively associated with the level of anti-HBs (rs=-0.42,P＜0.01).The level of IL-6 was negatively correlated with the level of IL-12 in the neonatal period and the infantile period (rs=-0.68,-0.70,P＜0.01).Conclusions IL-6 might promote the immune response to hepatitis B vaccination in infants whose mothers were HBsAg-positive,while IL-12 might inhibit the immune response.IL-6 and IL-12 would affect the immune response to hepatitis B vaccination in infants of HBsAg-positive mothers at the same time.

Relationship between HBeAg from HBsAg positive mothers and regulatory T cells in neonates and its influence on HBV intrauterine transmission / 中华流行病学杂志

Objective To explore the relationship between HBeAg in HBsAg positive mothers and CD4 + CD25 + Foxp3 + regulatory T cells (Treg) in newborns,as well as how they would influence the increasing risk on HBV intrauterine transmission.Methods We collected information on general demographic characteristics and delivery on 270 HBsAg positive mothers and their newborns from the Third People's Hospital of Taiyuan.Fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescence immunoassay (CLIA) were used to detect HBV DNA and HBV serological markers in peripheral blood from both mothers and neonates.The expression of Treg and other immune cells in peripheral blood of neonates were detected with flow cytometry (FCM).Results Maternal HBeAg positive rates were associated with an increased risk of intrauterine transmission (0R=4.08,95％ CI:1.89-8.82).Rates of T.reg in newborns born to HBsAg-positive mothers were higher than that of the negative group (Z=2.29,P=0.022).Each pair of the subjects was assigned to five different groups according to the HBeAg titers of mothers.Frequencies of both Treg and HBeAg in newboms and HBV DNA in mothers between the above said 5 groups showed similar trends of changing patterns and the differences between groups were statistically significant (x2=18.73,P＜0.001;x2=181.60,P＜0.001;x2=183.09,P＜0.001).Results from partial correlation analysis showed that after adjusting for neonatal HBeAg and maternal HBV DNA,mother's HBeAg titers were positively related to the percentage of Treg in their newboms (rs=0.19,P=0.039).In addition,the frequencies of Treg were negatively correlated with pDC and CD4 + T cell in their newborns (rs=-0.21,P=0.017;r,=-0.23,P=0.009).Conclusion HBeAg from HBsAg positive mothers might have inhibited the function of neonatal DC cells and T cells to reduce the immune response to HBV by up-regulating the proportion of Treg and finally increased the risk of HBV intrauterine transmission.

Influencing factors for non/low-response to hepatitis-B vaccine in infants of HBsAg positive mothers / 中华流行病学杂志

Objective To investigate the influencing factors for non/low-response to hepatitis B vaccine in infants of HBsAg-positive mothers.Methods A total of 286 HBsAg-positive pregnant women and their infants were recruited from the Third People's Hospital of Taiyuan during July 2011 to January 2013.The infants were immunized with hepatitis B vaccine according to the 0-1-6 month vaccination schedule and followed up for 12 months.The serum HBV DNA level of mothers,neonates and infants were detected by electro chemilum inescence immunoassay kits and fluorescene quantiative polymerase chain rection.Results Among 286 infants,the rate of non/low-response to hepatitis B vaccine was 18.53％ (53/286).Non-conditional logistic regression analysis indicated that the mother's HBV DNA level ≥ 1 × 107 copies/ml (0R=2.592,95％CI:1.121-5.996) and natural birth (OR=1.932,95％CI:1.021-3.654) were the risk factors for non/low-response to hepatitis B vaccine,the risks were 2.592 times and 1.932 times higher compared with the infants whose mothers were HBV DNA negative and the infants whose mothers had cesarean delivery.There was no multiplicative or additive interaction between high HBV DNA load and natural birth (OR=1.055,95％CI:0.209-5.321),(RERI=1.617,95％CI:-4.038-7.272;AP=0.364,95％CI:-).527-1.225;SI=1.195,95％CI:0.270-13.135).After stratified analysis of mother's HBV DNA level,delivery mode of mothers was not associated with non/low-response of their infants.Conclusion The mother's load of HBV DNA ≥ 1 × 107 copies/ml might be the factor for non/low-response to hepatitis B vaccine in infants of HBsAg positive mothers.

Effect of interleukin-6 and interleukin-12 on immune response to hepatitis B vaccination in infants of HBsAg-positive mothers / 中华流行病学杂志

Objective To explore the effect of interleukin-6 (IL-6) and Interleukin-12(IL-12) on immune response to hepatitis B vaccination in infants of HBsAg-positive mothers.Methods A total of 91 neonates whose mothers were HBsAg-positive were included and followed up for 12 months.HBV DNA and HBV serological markers in the peripheral blood of the neonates and infants were detected with fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescence immunoassay (CLIA),and the levels of IL-6 and IL-12 in the peripheral blood of the neonates and infants were detected with enzyme-linked immunosorbent assay (ELISA).Results The non-/hypo-response rate to hepatitis B vaccination was 35.16％ (32/91) in the 91 infants.In the neonatal period and infantile period,the level of IL-6 in non-/hypo-response group was lower than that in high-response group,while the level of IL-12 was higher than that in high-response group,and there was significant difference (P＜0.01).From the neonatal period to the infantile period,the level of IL-6 increased,while the level of IL-12 descended in both groups,and there was significant difference (P＜0.01).Furthermore,the level of anti-HBs of infants was positively correlated with the level of IL-6 (rs =0.70,0.79,P＜ 0.01),and was negatively correlated with the level of IL-12 (rs=-0.71,-0.72,P＜0.01) in the neonatal period and the infantile period.From the neonatal period to the infantile period,the increased level of IL-6 was positively associated with the level of anti-HBs (rs =-0.74,P＜0.01),while the decreased level of IL-12 was negatively associated with the level of anti-HBs (rs=-0.42,P＜0.01).The level of IL-6 was negatively correlated with the level of IL-12 in the neonatal period and the infantile period (rs=-0.68,-0.70,P＜0.01).Conclusions IL-6 might promote the immune response to hepatitis B vaccination in infants whose mothers were HBsAg-positive,while IL-12 might inhibit the immune response.IL-6 and IL-12 would affect the immune response to hepatitis B vaccination in infants of HBsAg-positive mothers at the same time.

Relationship between HBeAg from HBsAg positive mothers and regulatory T cells in neonates and its influence on HBV intrauterine transmission / 中华流行病学杂志

Objective To explore the relationship between HBeAg in HBsAg positive mothers and CD4 + CD25 + Foxp3 + regulatory T cells (Treg) in newborns,as well as how they would influence the increasing risk on HBV intrauterine transmission.Methods We collected information on general demographic characteristics and delivery on 270 HBsAg positive mothers and their newborns from the Third People's Hospital of Taiyuan.Fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescence immunoassay (CLIA) were used to detect HBV DNA and HBV serological markers in peripheral blood from both mothers and neonates.The expression of Treg and other immune cells in peripheral blood of neonates were detected with flow cytometry (FCM).Results Maternal HBeAg positive rates were associated with an increased risk of intrauterine transmission (0R=4.08,95％ CI:1.89-8.82).Rates of T.reg in newborns born to HBsAg-positive mothers were higher than that of the negative group (Z=2.29,P=0.022).Each pair of the subjects was assigned to five different groups according to the HBeAg titers of mothers.Frequencies of both Treg and HBeAg in newboms and HBV DNA in mothers between the above said 5 groups showed similar trends of changing patterns and the differences between groups were statistically significant (x2=18.73,P＜0.001;x2=181.60,P＜0.001;x2=183.09,P＜0.001).Results from partial correlation analysis showed that after adjusting for neonatal HBeAg and maternal HBV DNA,mother's HBeAg titers were positively related to the percentage of Treg in their newboms (rs=0.19,P=0.039).In addition,the frequencies of Treg were negatively correlated with pDC and CD4 + T cell in their newborns (rs=-0.21,P=0.017;r,=-0.23,P=0.009).Conclusion HBeAg from HBsAg positive mothers might have inhibited the function of neonatal DC cells and T cells to reduce the immune response to HBV by up-regulating the proportion of Treg and finally increased the risk of HBV intrauterine transmission.

Influence factors of quantitative changes of dendritic cells in neonate born to HBsAg positive mother / 中华传染病杂志

Objective To investigate the influence factors of quantitative changes of dendritic cells (DC) in neonate born to HBsAg positive mother.Methods Sixty HBsAg positive mothers and their newborns were enrolled from the Third People's Hospital of Taiyuan from July 2011 to March 2012.The serum hepatitis B virus (HBV) markers and HBV DNA in mothers and newborns before vaccination were determined by chemiluminescence immunoassay (CLIA) and fluorescence quantitative polymerase chain reaction (PCR).The circulating frequencies of DC subsets were determined in the newborns by flow cytometry (FCM).The comparison of data was done by Mann-Whitney test and t test.The correlation analysis was done by Spearman rank correlation analysis and chi square test.Results Among 60 newborns,5 were HBsAg positive and HBV DNA negative.Among 60 HBsAg positive mothers,21 were HBeAg positive and 29 were HBV DNA positive.There was no significant quantitative difference of neonatal myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC) between intrauterine infection group and intrauterine non-infection group (Z=-0.535,P=0.59 and Z=-0.027,P=0.98,respectively).However,mother's HBeAg positive status was closely related with neonatal HBeAg positive status (Pearson contingency coefficient was 0.928,P＜0.01).The frequencies of mDC in newborns born to HBeAg positive mothers were significantly lower than those born to HBeAg negative mothers (0.60±0.57 vs 0.87±0.58; Z=-2.085,P＜0.05).However,there was no significant quantitative differences of mDC and pDC between newborns born to HBV DNA positive mothers and born to negative mothers (Z=-1.272,P=0.20 and Z=-0.806,P=0.42,respectively).The frequencies of pDC were significantly lower in newborns born to mothers with HBV DNA＞ 1 × 107 copy/mL compared to newborns born to HBV DNA negative mothers (0.30±0.18 vs 0.64±0.55; t=-2.996,P=0.005).Conclusions HBeAg positive status of mothers may reduce neonatal frequencies of mDC.Neonatal frequencies of pDC may be reduced when the mothers' HBV DNA loads are more than 1 × 107 copy/mL.