Abstract
BackgroundChronic 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 FindingsThis 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.ConclusionsA 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.
Highlights
Preterm birth is the leading cause of perinatal mortality and morbidity worldwide [1]
Chronic chorioamnionitis is histologically characterized by maternal T cell infiltration in the chorionic trophoblast layer or chorioamniotic connective tissue layer
To determine whether anti-human leukocyte antigen (HLA) antibodies play a role in spontaneous preterm birth, anti-HLA seropositivity of women presenting with spontaneous preterm birth was compared to cases of normal term birth (Figure 2B)
Summary
Preterm birth is the leading cause of perinatal mortality and morbidity worldwide [1]. The rate of preterm birth has been rising in most developed countries, ranging from 5% to 13% of all deliveries [2,3]. While preterm birth is known to be associated with various obstetric disorders such as intra-uterine infection/inflammation and preeclampsia [1,6], the causes and precise mechanisms are not fully understood. The elucidation of the essential pathophysiology of different types of preterm birth is an urgent and important matter. Chronic chorioamnionitis is found in more than one-third of spontaneous preterm births. We investigated whether there was evidence for antibody-mediated rejection against the fetus in spontaneous preterm birth
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