[Effect of intrauterine hepatitis B virus infection on peripheral blood mononuclear cells interferon-gamma and interleukin-4 in newborns].
OBJECTIVE
To observe the effect of intrauterine hepatitis B virus (HBV) infection on peripheral blood mononuclear cells function of secreting interferon-gamma and interleukin-4.


METHODS
Pregnant women were systematically screened for HBsAg and HBeAg when attending the antenatal clinic at the Qinhuangdao Maternal and Child Health Hospital. Totally 67 pairs of mothers and infants were enrolled into this study after obtaining the women's consent. Venous blood samples were collected from the infants within 6 hours after birth and before HBIG injection and HBVac immunization. Blood sample was taken from the mother at or after the time when the infant was born. HBV DNA in plasma and PBMC from mothers and their newborns were examined using polymerase chain reaction (PCR). According to HBV DNA in PBMC of newborns, they were divided into two groups. The PBMCs isolated from newborn were cultured with purified HBsAg or phytohemagglutinin (PHA). The supernatant interleukin-4 and interferon-gamma level was measured by using enzyme linked immunosorbent assay (ELISA).


RESULTS
In 19 newborns PBMC was positive for HBV DNA. Maternal PBMC HBV DNA positivity was associated with high rate of intrauterine HBV infection in the infants (chi2 = 7.58, P < 0.01). Compared with the infants whose PBMC HBV DNA was negative, the infants with PBMC positive for HBV DNA expressed a lower level interferon-gamma secretion after purified HBsAg stimulation (t = 4.71, P < 0.01), however, no significant difference was seen after PHA stimulation (t = 1.21, P > 0.05). The supernatant IL-4 level detected after stimulation with purified HBsAg was higher in the newborns whose PBMC HBV DNA was positive as compared with those negative for PBMC HBV DNA (t = -8.51, P < 0.05). The level of IL-4 did not show any significant difference after stimulation with PHA between the PBMC HBV DNA negative and positive groups (t = -2.40, P > 0.05).


CONCLUSIONS
Infection with HBV of maternal PBMC is responsible for perinatal newborn's PBMC HBV infection and it may be an important route of HBV vertical transmission. Infants whose mothers were positive for HBsAg, HBeAg and HBV DNA were at extraordinarily high risk for hepatitis B virus infection. PBMC infected with HBV could influence the status of humoral and cellular immunity resulting in persistent HBV infection and recurrent mother to infant transmission of HBV. Low responses of interferon-gamma and high interleukin-4 transcription upon specific stimulation exist in infants whose PBMC were positive for HBV DNA in uterus may contribute to immune tolerance to HBV.
Su
Xue-song
XS
Department of Obstetrics and Gynecology, Qinhuangdao Maternal and Child Health Hospital, Qinhuangdao 066000, China.
Peng
Xun
X
Chen
Yan-hua
YH
Wang
Rui-hua
RH
Ma
Jie
J
Tong
Yan
Y
D004279:DNA, Viral / Q000097:blood; D005260:Female; D006509:Hepatitis B / Q000097:blood / Q000635:transmission*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus; D006801:Humans; D007108:Immune Tolerance; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D007371:Interferon-gamma / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D015847:Interleukin-4; D007371:Interferon-gamma