Analysis of total Hla-G Levels and its isoforms in placental malaria

Abstract

The present study examined the total, membrane bound and soluble HLA-G in infected and uninfected placentas using quantitative real time PCR, ELISA and immunohistochemistry. The total HLA-G transcripts differed significantly (p = 0.009) between infected and uninfected primigravidae. The membrane bound HLA-G transcripts were significantly more abundant than the soluble HLA-G in infected placentas (p = 0.04) in all mothers. At the protein level infected placentas had higher mean levels of soluble HLA-G than uninfected and naïve sera. Soluble HLA-G concentration differed significantly between infected and uninfected primigravidae with a p of 0.001. Immunohistochemistry study demonstrated intense staining of HLA-G in infected placentas, with localization of membrane bound HLA-G protein in the syncytiotrophoblasts and near immune cells, when compared to uninfected placentas. Soluble HLA-G localized in the intervillous spaces and in the lumen of the stroma of forming fetal blood vessels. Soluble HLAG concentrations in infected primigravidae and secundagravidae were negatively correlated to birth weight. Conversely, the concentration in infected multigravidae was positively correlated to birth weight and maternal age. Maternal age and the concentration of soluble HLA-G correlated negatively in all parities in a physiological pregnancy. However, in infected primigravidae and multigravidae the maternal age and soluble HLA-G correlated positively. The findings of this study indicate that there are high levels of HLA-G in infected placentas from all parities compared to the uninfected placentas. However, the levels of HLA-G in infected primigravidae are significantly higher than in uninfected with p value of 0.001. These results shows that HLAG is involved in mediating anti-inflammatory response in P. falciparum infected placentas. The study findings suggest that interventions during pregnancy malaria should promote expression of HLA-G in the placenta to check down the effects of the inflammatory infiltrates in the P. falciparum infected placenta.