Connection between human leucocyte antigens D region and T helper cytokines in preeclampsia

Abstract.

Preeclampsia is a common and major cause of maternal and perinatal morbidity and mortality. Human leucocyte antigen (HLA) susceptibility and impaired adaptation of the T lymphocyte sub-population and a bi-directional effect of T helper cytokines on the outcome of pregnancy have been reported in patients with preeclampsia. The association between maternal HLA class II and T helper cytokines in women with preeclampsia was investigated in seventy-six preeclamptic women and normotensive controls using Terasaki microlymphocytotoxicity test. T helper cytokines interleukin (IL)-8, IL-6, IL-4, tumour necrosis factor (TNF)-α and interferon (IFN)-γ were estimated in the maternal blood and placenta by enzyme-linked immunosorbent assay (ELISA). Histopathological evaluation of the placenta was also carried out. HLA class II DR2, DR4, DR5, DRw8, DRw10, DRw11, DRw18, and DQw2 had significant relative risk ratios for preeclampsia, while DQw3 was more common in the controls. DR4-DRw11-DQw2 haplotype was more common in preeclamptic women with intrauterine growth restriction, low birth weight and placental weight, increased expression of T helper cytokines IL-8, TNF-α and IFN-γ and abnormal uteroplacental vasculature. These findings suggest that HLA class II DR4-DRw11 -DQw2 haplotypes may be associated with preeclampsia with intrauterine growth restriction through low placental weight from impaired placental development, as a result of increased expression of T helper 1 cytokines IL-8, TNF-α and IFN-γ.