The role of trophoblast cell receptor expression in HIV-1 passage across the placenta in pre-eclampsia: an observational study

Abstract

Objective To compare expression of markers of HIV and associated receptors (p24, CD4, CCR5 and ICAM-2) in placentae and umbilical cords of HIV-associated and pre-eclamptic pregnancies to elucidate any association between these conditions in mother-to-child transmission.

Design Cross-sectional immunohistochemical analysis of target receptor expression.

Setting Laboratory-based study of primigravidae attending a district hospital in South Africa.

Population or sample Retrospectively collected placental tissue (stratified into four groups according to HIV status of normotensive and pre-eclamptic participants (n = 20/group).

Method Immunohistochemistry utilising CD4 (1:1), p24 (1:10), CCR5 (1:80) and ICAM-2 (1:100) antibodies was performed using light microscopy for image acquisition and analysis.

Main outcome measures Evaluate the expression of receptors on syncytiotrophoblast involved in in utero transmission of HIV.

Results Syncytiotrophoblast was immunopositive for CD4 and CCR5 antibody with greater expression of CCR5 in HIV-positive versus HIV-negative groups (F1,159 = 6.979, P = 0.009) and normotensive versus pre-eclamptic groups (F1,159 = 8.803, P = 0.003). p24 was present in both placentae and umbilical cords of babies that were HIV-negative at 6 weeks. ICAM-2 immunostaining was observed in the syncytiotrophoblast across study groups and was significantly higher in the HIV-negative pre-eclamptic group (v2 (3) = 45.3; P < 0.001).

Conclusion Concurrent CD4 and CCR5 receptor expression demonstrates possible in utero viral entry routes across the placental barrier. ICAM-2 expression may influence HIV passage across the placenta or restoration of risk of pre-eclampsia in HAART-treated mothers. HIV was found in fetal circulation regardless of antiretroviral treatment. Further confirmatory ultrastructural and molecular work is warranted.