Soluble human leukocyte antigen -G during pregnancy and infancy in Benin: Mother/child resemblance and association with the risk of malaria infection and low birth weight

Abstract

Human leukocyte antigen (HLA) G is a tolerogenic molecule involved in the maternal-fetal immune tolerance phenomenon. Its expression during some infectious diseases leading to immune evasion has been established. A first study conducted in Benin has shown that the production of soluble HLA-G (sHLA-G) during the first months of life is strongly correlated with the maternal level at delivery and associated with low birth weight and malaria. However sHLA-G measurements during pregnancy were not available for mothers and furthermore, to date the evolution of sHLA-G in pregnancy is not documented in African populations. To extend these previous findings, between January 2010 and June 2013, 400 pregnant women of a malaria preventive trial and their newborns were followed up in Benin until the age of 2 years. Soluble HLA-G was measured 3 times during pregnancy and repeatedly during the 2 years follow-up to explore how sHLA-G evolved and the factors associated. During pregnancy, plasma levels of sHLA-G remained stable and increased significantly at delivery (p<0.001). Multigravid women seemed to have the highest levels (p = 0.039). In infants, the level was highest in cord blood and decreased before stabilizing after 18 months (p<0.001). For children, a high level of sHLA-G was associated with malaria infection during the follow-up (p = 0.02) and low birth weight (p = 0.06). The mean level of sHLA-G during infancy was strongly correlated with the mother's level during pregnancy (<0.001), and not only at delivery. Moreover, mothers with placental malaria infection had a higher probability of giving birth to a child with a high level of sHLA-g (p = 0.006). High sHLA-G levels during pregnancy might be associated with immune tolerance related to placental malaria. Further studies are needed but this study provides a first insight concerning the potential role of sHLA-G as a biomarker of weakness for newborns and infants.

Fig 1. Evolution of the mean level (and 95 confidence intervals) of soluble HLA-G during pregnancy.

⁽*⁾ indicates that the level of sHLA-G is significantly higher at delivery (p<0.001; Kruskal-Wallis test). (≤3 months: n = 26, SD: 12.39, 4 months: n = 65, SD: 13.92, 5 months: n = 177, SD: 17.01, 6 months: n = 254, SD: 11.48, 7 months: n = 131, SD: 15.20, 8 months: n = 115, SD: 12.09, 9 months: n = 360, SD: 35.11).

Fig 2. Evolution of the mean level of soluble HLA-G in the first two years of life (p<0.001 for the overall evolution; mixed Tobit model).

⁽*⁾ The mean level of soluble HLA-G in infants at 18 and 24 months are not significantly different (p = 0.77).

Fig 3. Predicted evolution of sHLA-G from birth to 24 months for low birth weight versus normal birth weight children.

Fig 4. Mother/child resemblance: Probability of newborn to have a profile according to the mother profile.