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.