Date Published: February 6, 2017
Publisher: Public Library of Science
Author(s): Tania C. d’Almeida, Ibrahim Sadissou, Jacqueline Milet, Gilles Cottrell, Amandine Mondière, Euripide Avokpaho, Laure Gineau, Audrey Sabbagh, Achille Massougbodji, Kabirou Moutairou, Eduardo A. Donadi, Benoit Favier, Edgardo Carosella, Philippe Moreau, Nathalie Rouas-Freiss, David Courtin, André Garcia, Sylvie Bisser.
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.
Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I antigen that differs from the others HLA class I molecules in its limited polymorphism, its restricted tissue distribution and its particular expression . Alternative splicing encodes four membrane-bound and three soluble isoforms. The main isoforms present in the plasma are soluble HLA-G1 and -G5 . HLA-G also differs from the HLA class I molecule by exerting inhibitory functions on immune responses [3–5].
The women’s mean age was 25.9 years (95% confidence interval [25.4–26.4]; range, 18–42). The first ANV occurred before 29 GW and 15.7% were primigravid. Throughout the follow-up, 27.7% of women developed peripheral malaria and 10.9% had placental malaria at delivery.
The present study is the first conducted in an African population describing the physiological evolution of the sHLA-G level during pregnancy. This work complements a study conducted in Benin that found a strong correlation between maternal sHLA-G level at delivery and children’s levels during the first years of life as well as an association between the infant’s level and LBW and malaria . However, in this study mothers were included at delivery and pregnancy data were not available. Associations between both malaria and LBW and the infant’s sHLA-G level were confirmed here. Furthermore, the correlation between the mother’s and the child’s sHLA-G levels was reinforced since we showed that the child’s level throughout the follow-up was correlated with its mother’s level at each measurement. Finally, mothers with placental malaria gave birth to children with high sHLA-G profile during infancy. This last result is consistent with the fact that the immune tolerance described in case of placental malaria [22–24] could be correlated with sHLA-G levels and that placental malaria might be considered as a marker of a more complex phenomenon involving the tolerogenic molecule HLA-G.