[Expression of HLA-G protein in placental tissues and its influence on Th1/Th2 cytokines in peripheral blood in patients with intrahepatic cholestasis of pregnancy]

Abstract

Objective: To investigate the changes of human leukocyte antigen-G (HLA-G) protein expression and Th1/Th2 type cytokines in intrahepatic cholestasis of pregnancy (ICP) and their relativity to the etiology of ICP.

Methods: Peripheral blood and placental tissues were obtained from 26 ICP patients (the ICP group) and 22 normal pregnant women (the NP group) in the operation room for Cesarean birth. Immunohistochemistry was used to detect the expression of HLA-G protein in the placental tissues. Meanwhile we tested the concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4) by enzyme-linked immunosorbent assay (ELISA) in the peripheral blood and checked the levels of TBA in the serum.

Results: TBA level in the ICP group was (27.05+/-6.08) micromol/L, significant higher than that in the NP group (4.35+/-2.68) micromol/L (P<0.01). The positive expression of HLA-G protein in extravillous trophoblast in the ICP group was significantly lower than that in the NP group (P<0.01). The mean optical density (MOD) of positive expression of HLA-G protein in the placenta tissues in the ICP group (52.91+/-7.19) was significantly lower than that in the NP group (69.26+/-7.72) (P<0.01). The concentration of TNF-alpha was significantly higher in the ICP group (101.31+/-19.30) pg/mL than that in the NP group (54.51+/-23.72) pg/mL (P<0.01). The concentration of IL-4 was lower in the ICP group (22.16+/-6.55) pg/mL than that in the NP group (31.69+/-8.25) pg/mL (P<0.01). The ratio of TNF-alpha/IL-4 was higher in the ICP group (4.52+/-1.91) than that in the NP group (1.72+/-0.61) (P<0.01). There was a negative correlation between the MOD of HLA-G protein and TNF-alpha (r=-0.98, P<0.01) in the ICP group. No correlation with IL-4 and TNF-alpha/IL-4 was seen (P>0.05). There was a positive correlation between TBA and TNF-alpha (r=0.99, P<0.01), and a negative correlation between TBA and the MOD of HLA-G protein (r=-1.00, P<0.01) in the ICP group. No correlation with IL-4 and TNF-alpha/IL-4 was seen (P>0.05).

Conclusion: There is an imbalance of Th1/Th2 cytokines to the Th1 type in the peripheral blood of ICP patients. The expression of HLA-G protein in the placenta of ICP patients decreases, leading to an increase of Th1 type cytokines that may be one of the reasons for liver destroy in ICP.