Increased human leukocyte antigen-G expression at the maternal-fetal interface is associated with preterm birth

Abstract

Abstract Objective: The maternal-fetal interface must modulate immune function to allow tolerance of fetal cells while still reacting to pathogens to suppress infection. Human leukocyte antigen-G (HLA-G) is a class Ib major histocompatibility complex protein involved in maternal-fetal tolerance. We posited that alterations in placental HLA-G expression predispose women to preterm birth. The aim of this study was to compare HLA-G expression in the maternal-fetal interface of term versus preterm human placentas.

Methods: We performed a cross-sectional study of specimens from the basal plate of the human placenta from women enrolled in a tissue specimen and clinical data consortium. Immunohistochemistry with digital microscopic analysis was used to quantify HLA-G protein expression in the basal plate from preterm and term placentas.

Results: Preterm birth <37 weeks occurred in 29.5% of 149 singleton pregnancies. HLA-G-positive cells occupied one-third of the basal plates, and the HLA-G-positive area was increased by 14% in placentas from preterm births than in those from term births (32.1% in term placentas versus 36.6% in preterm placentas).

Conclusion: Although HLA-G is required for maternal tolerance of the semi-allogeneic fetus, higher levels of HLA-G expression at the maternal-fetal interface is associated with preterm birth.

Keywords: Extravillous trophoblast; infection; maternal–fetal tolerance; placenta.

Figure 1

Digital microscopy of basal plate with HLA-G positive cells labeled dark brown (left) and Visiomorph image analysis (right) after classification of HLA-G positive cells (red) and HLA-G negative cells (blue).