Introduction
SGA neonates, defined as “neonates with birthweight less than 10th centile for a specific gestational age and sex”1 are at a greater risk of death, lung disease, hypotension, necrotizing enterocolitis, poor thermoregulation, polycythemia, insulin resistance, type II diabetes mellitus, cardiovascular diseases (like hypertension), stunted growth, poor neurodevelopment outcomes and cognitive impairments2,3,4.
One of the various maternal and fetal risk factors associated with SGA births, is the aberrant immunological interactions in the placenta. The precise mechanisms steering the tolerance of semi-allogeneic fetus by mother are not completely elucidated, however, one of them is the expression of Human Leukocyte Antigen–G (HLA-G) protein in extra-villous trophoblasts in the placenta5. A difference in the HLA-G expression has been reported as one of the causes of aberrant immunological interactions in the placenta6.
HLA-G is known to perform a crucial role in establishment and maintenance of pregnancy by abrogating the activation of maternal immune cells5,6. HLA-G directly binds to inhibitory receptors (ILT-2, ILT-4, and KIR2DL4) that are expressed by monocytes, B cells, T cells and NK cells; monocytes and dendritic cells; and CD56 NK cells, respectively7. These interactions also trigger the release of cytokines and chemokines which signal placental development and remodeling of maternal uterine spiral arteries8,9.
HLA-G expressed in its soluble form in the placenta may enter maternal circulation as it has been observed that circulatory sHLA-G levels are 2-5 folds higher in pregnant women versus their non-pregnant counterparts10. Aberrant levels of sHLA-G protein in the peripheral circulation and in the placenta (mRNA/protein) of pregnant females is linked to pregnancy complications, like preeclampsia, intrauterine growth restriction (IUGR) and adverse birth outcomes like recurrent pregnancy loss (RPL), and premature birth11,12,13,14,15. Moreover, low HLA-G expression in human embryo culture supernatants was found to be correlated to their poor implantation in the in-vitro fertilization process in humans16, 17.
HLA-G expression in adequate amount at the maternal-fetal interface during pregnancy is essential. However, there is currently no data available on the progression of HLA-G throughout pregnancy in the Indian population. The lack of studies exploring the association of sHLA-G levels with SGA births in India emphasizes the need for its investigation. Hence, we aim to study and compare the trajectories of sHLA-G expression in the sera of pregnant women delivering SGA or AGA neonates.