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

Joon Ho Lee, Roberto Romero, Yi Xu, Jung Sun Kim, Vanessa Topping, Wonsuk Yoo, Juan Pedro Kusanovic, Tinnakorn Chaiworapongsa, Sonia S. Hassan, Bo Hyun Yoon, Chong Jai Kim

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Abstract

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.

Original languageEnglish (US)
Article numbere16806
JournalPloS one
Volume6
Issue number2
DOIs
StatePublished - Feb 17 2011

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Lee, J. H., Romero, R., Xu, Y., Kim, J. S., Topping, V., Yoo, W., Kusanovic, J. P., Chaiworapongsa, T., Hassan, S. S., Yoon, B. H., & Kim, C. J. (2011). A signature of maternal anti-fetal rejection in spontaneous preterm birth: Chronic chorioamnionitis, anti-human leukocyte antigen antibodies, and C4d. PloS one, 6(2), [e16806]. https://doi.org/10.1371/journal.pone.0016806