Journal
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
Volume 70, Issue 2, Pages 162-175Publisher
WILEY
DOI: 10.1111/aji.12141
Keywords
Flow cytometry; preterm birth; rejection; transplantation
Categories
Funding
- Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH)
- NICHD, NIH [HHSN275201300006C]
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Problem Maternal anti-fetal rejection is a mechanism of disease in spontaneous preterm labor. The objective of this study was to determine whether the presence of human leukocyte antigen (HLA) panel-reactive antibodies (PRA) during the second trimester increases the risk of spontaneous preterm delivery. Methods of study This longitudinal case-control study included pregnant women with spontaneous preterm deliveries (n = 310) and control patients with normal term pregnancies (n = 620), matched for maternal age and gravidity. Maternal plasma samples obtained at 14-16, 16-20, 20-24, and 24-28weeks of gestation were analyzed for HLA class I and class II PRA positivity using flow cytometry. The fetal HLA genotype and maternal HLA alloantibody epitope were determined for a subset of patients with positive HLA PRA. Results (i) Patients with spontaneous preterm delivery were more likely to exhibit HLA class I (adjusted OR=2.54, P<0.0001) and class II (adjusted OR=1.98, P=0.002) PRA positivity than those delivering at term; (ii) HLA class I PRA positivity for patients with spontaneous preterm delivery between 28 and 34weeks (adjusted OR=2.88; P=0.001) and after 34weeks of gestation (adjusted OR=2.53; P<0.0001) was higher than for those delivering at term; (iii) HLA class II PRA positivity for patients with spontaneous preterm delivery after 34weeks of gestation was higher than for those delivering at term (adjusted OR=2.04; P=0.002); (iv) multiparous women were at a higher risk for HLA class I PRA positivity than nulliparous women (adjusted OR=0.097, P<0.0001 for nulliparity); (v) nulliparous women had a higher rate of HLA class I PRA positivity with advancing gestational age (P=0.001); and (vi) 78% of women whose fetuses were genotyped had alloantibodies specific against fetal HLA class I antigens. Conclusion Pregnant women with positive HLA class I or class II PRA during the second trimester are at an increased risk of spontaneous preterm delivery due to antibody-mediated maternal anti-fetal rejection.
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