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.