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

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.

• Extravillous trophoblast
• infection
• maternal–fetal tolerance
• placenta

Acknowledgements

We thank Dr. D. Michael Nelson for comments, and Dr. Krzysztof Hyrc and Mr. Gary London in the Alafi Neuroimaging lab for their expertise in digital microscopy and image analysis. We thank Carolyn Bower, Ms. Rebecca Gunkel, and Ms. Qiuhong Zhao for their assistance with this study, and Dr. Deborah Frank for editorial assistance.

Declaration of interest

The authors report no declarations of interest. Dr. Stout is supported by Washington University CTSA Grant (UL1 TR000448) and NICHD T32 (5 T32 HD055172-02). Digital microscopy and image analysis were supported by the Alafi Neuroimaging Laboratory at Washington University in Saint Louis (National Institute of Health Neuroscience Blueprint Interdisciplinary Center Core Grant P30 NS057105). Dr. Mysorekar is supported by a Preventing Prematurity Initiative Grant from the Burroughs Wellcome Fund and a Prematurity Research Initiative Investigator award from the March of Dimes. The Women and Infants’ Health Specimen Consortium is supported by grants from the Washington University ICTS (NIH UL1 RR024992).