A signature of maternal anti-fetal rejection in spontaneous preterm birth: chronic chorioamnionitis, anti-human leukocyte antigen antibodies, and C4d.

BACKGROUND: Chronic chorioamnionitis is found in more than one-third of spontaneous preterm births. Chronic chorioamnionitis and villitis of unknown etiology represent maternal anti-fetal cellular rejection. Antibody-mediated rejection is another type of transplantation rejection. We investigated whether there was evidence for antibody-mediated rejection against the fetus in spontaneous preterm birth. METHODS AND FINDINGS: This cross-sectional study included women with (1) normal pregnancy and term delivery (n = 140) and (2) spontaneous preterm delivery (n = 140). We analyzed maternal and fetal sera for panel-reactive anti-HLA class I and class II antibodies, and determined C4d deposition on umbilical vein endothelium by immunohistochemistry. Maternal anti-HLA class I seropositivity in spontaneous preterm births was higher than in normal term births (48.6% vs. 32.1%, p = 0.005). Chronic chorioamnionitis was associated with a higher maternal anti-HLA class I seropositivity (p<0.01), significant in preterm and term birth. Villitis of unknown etiology was associated with increased maternal and fetal anti-HLA class I and II seropositivity (p<0.05, for each). Fetal anti-HLA seropositivity was closely related to maternal anti-HLA seropositivity in both groups (p<0.01, for each). C4d deposition on umbilical vein endothelium was more frequent in preterm labor than term labor (77.1% vs. 11.4%, p<0.001). Logistic regression analysis revealed that chronic chorioamnionitis (OR = 6.10, 95% CI 1.29-28.83), maternal anti-HLA class I seropositivity (OR = 5.90, 95% CI 1.60-21.83), and C4d deposition on umbilical vein endothelium (OR = 36.19, 95% CI 11.42-114.66) were associated with preterm labor and delivery. CONCLUSIONS: A major subset of spontaneous preterm births has a signature of maternal anti-fetal cellular and antibody-mediated rejections with links to fetal graft-versus-host disease and alloimmune reactions.

NK cells and surveillance in humans.

Natural killer (NK) cells are part of the innate immune system and help to protect against infections and tumour transformation by eliminating affected cells. NK cells become activated upon target cell recognition through the integration of signals provided by both activating and inhibitory receptors. Ligands recognized by these receptors include major histocompatibility complex class I, stress-induced molecules, adhesion proteins and other molecules that are used by NK cells to identify cells to be killed. This recognition constitutes the basis of NK immunosurveillance, and its full understanding is important for therapeutic purposes, such as haploidentical bone marrow transplantation for haematological malignancies. Human NK cells are also found abundantly in the uterine decidua during early pregnancy. Besides a detrimental role in reaction to the semi-allogeneic fetus, these uterine NK cells help to create a balanced environment for the conceptus, influencing important processes such as blastocyst implantation, trophoblast invasion and spiral artery development. This review summarizes the different aspects of human NK cell biology implicated in immunosurveillance.