ABSTRACT
This study determined the effect of hepatitis B virus (HBV) replication in peripheral blood mononuclear cell (PBMC) from HBsAg-positive mothers on HBV intrauterine transmission. A total of 150 HBsAg-positive mothers and their neonates were recruited in this study. Within 24 h after birth, HBV serological markers, serum HBV DNA, PBMC HBV relaxed circular DNA (rcDNA), and covalently closed circular DNA (cccDNA) were measured in the HBsAg-positive mothers and their neonates before passive-active immune prophylaxis. The relationship between HBV replication in PBMC and HBV intrauterine transmission was examined through Chisquare test and logistic regression. The rate of HBV intrauterine transmission was 8.00% (12/150) in the 150 neonates born to HBsAg-positive mothers. The positivities of PBMC HBV rcDNA and cccDNA in the HBsAg-positive mothers were 36.67% (55/150) and 10% (15/150), respectively. Maternal PBMC HBV cccDNA was a risk factor of HBV intrauterine transmission (OR = 6.003, 95% CI: 1.249-28.855). Maternal serum HBeAg was a risk factor of PBMC HBV rcDNA (OR = 3.896, 95% CI: 1.929-7.876) and PBMC HBV cccDNA (OR = 3.74, 95% CI: 1.186-11.793) in the HBsAg-positive mothers. Administration of hepatitis B immune globulin was a protective factor of PBMC HBV cccDNA (OR = 0.312, 95%CI: 0.102-0.954) during pregnancy. The positivity of PBMC HBV rcDNA was related to that of cccDNA in the HBsAg-positive mothers (χ 2= 5.087, P = 0.024). This study suggests that PBMC is a reservoir of HBV and an extrahepatic site for virus replication and plays a critical role in HBV intrauterine transmission.
Subject(s)
Hepatitis B virus/physiology , Hepatitis B , Infectious Disease Transmission, Vertical/prevention & control , Leukocytes, Mononuclear/immunology , Pregnancy Complications, Infectious , Adult , DNA, Viral/analysis , Female , Hepatitis B/diagnosis , Hepatitis B/immunology , Hepatitis B/transmission , Humans , Infant, Newborn , Male , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/immunology , Risk Factors , Serologic Tests/methods , Virus Replication/immunologyABSTRACT
Objective: To explore the relationship between HBeAg in HBsAg positive mothers and CD(4)(+)CD(25)(+)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 (OR=4.08, 95%CI: 1.89-8.82). Rates of Treg 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 newborns 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(χ(2)=18.73, P<0.001; χ(2)=181.60, P<0.001; χ(2)=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 newborns (r(s)=0.19, P=0.039). In addition, the frequencies of Treg were negatively correlated with pDC and CD(4)(+) T cell in their newborns (r(s)=-0.21, P=0.017; r(s)=-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.
Subject(s)
Hepatitis B Surface Antigens , Hepatitis B e Antigens , Hepatitis B , Infectious Disease Transmission, Vertical , T-Lymphocytes, Regulatory , Biomarkers/blood , DNA, Viral , Female , Hepatitis B virus , Humans , Infant, Newborn , Mothers , Polymerase Chain Reaction , Pregnancy , Pregnancy Complications, InfectiousABSTRACT
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.
ABSTRACT
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.
