Human Leukocyte Antigens in Pregnancy and Preeclampsia

Abstract

Preeclampsia is a pregnancy-induced hypertensive disorder, the pathophysiology of which includes underlying maternal cardiovascular disease, deficient spiral artery remodeling during placenta development, and inflammatory immune responses at the maternal-fetal interface. Human leukocyte antigens (HLA) are major histocompatibility complex molecules essential for the recognition of foreign antigens that is central to immune defense against pathogens and critical determinants for the immune system discriminating between self and non-self tissues, such as in transplantation. Pregnancy represents a naturally existing “transplantation”, where the maternal immune system must be immunologically tolerant to the developing fetus which is 50% allogeneic. It is then unsurprising that HLA also influence normal pregnancy and pregnancy complications including preeclampsia. Here we review the role of classical and non-classical HLA molecules in influencing normal physiologic function during pregnancy and describe the association of HLA with pathophysiology in preeclampsia.

Biomarker role of maternal soluble human leukocyte antigen G in pre‐eclampsia: A meta‐analysis

“…The risk of bias was assessed using the Newcastle‐Ottawa Scale (NOS) 28 . The scale consists of 3 domains 1 Selection, 2 Comparability, and 3 Outcome where the study is judged and scores are assigned, 9 being the highest. Studies with scores ranging from 7 to 9, 4 to 6, and 0 to 3 were considered low‐risk, high risk and very high‐risk respectively.…”

“…Data extraction was performed on a pre‐specified data extraction sheet in Microsoft Excel®. Data relating to the following categories were extracted 1 : author and year, 2 study country, 3 number of PE cases, 4 number of controls, 5 Age of PE subjects, 6 trimesters of sHLA‐G estimations, 7 Gestational age at sampling, 8 gravidity, 9 estimation methodology, 10 sHLA‐G levels in PE cases, and 11 sHLA‐G levels in controls. Continuous data were reported as mean (standard deviation) or median (interquartile range).…”

“…The molecular mechanisms for the survival of the fetus in an antigenically different mother is enigmatic. 1 This process has been linked to immune tolerance via which maternal antibodies by fetal alloantigens are suppressed. 2 This suppressive mechanism takes place on the endometrial decidua, the site where the placental bed is established.…”

“…Pregnancy is a distinctive physiological event in which a semi‐allogeneic fetus survives in the uterus of the mother without being rejected, despite significant exchange in the circulation. The molecular mechanisms for the survival of the fetus in an antigenically different mother is enigmatic 1 . This process has been linked to immune tolerance via which maternal antibodies by fetal alloantigens are suppressed 2 .…”

Relationships between Polymorphisms in HLA-G 3’UTR Region and COVID- 19 Disease Severity

“…An increased risk of breast cancer and human cytomegalovirus infection (16) has been connected to the lack of 14-bp (deletion). In contrast, 14-bp (insertion) has been linked to preeclampsia, reproductive problems, and systemic lupus erythematosus (Aisagbonhi and Morris 2022). The relation between HLA-G 3'UTR genetic variants and sHLA-G has been investigated globally (Donadi et al 2011c).…”