Detection of Anti-HLA Antibodies in Maternal Blood in the Second Trimester to Identify Patients at Risk of Antibody-Mediated Maternal Anti-Fetal Rejection and Spontaneous Preterm Delivery
Article first published online: 10 JUL 2013
Published 2013. This article is a US Government work and is in the public domain in the USA.
American Journal of Reproductive Immunology
Volume 70, Issue 2, pages 162–175, August 2013
How to Cite
CitationDetection of anti-HLA antibodies in maternal blood in the second trimester to identify patients at risk of antibody-mediated maternal anti-fetal rejection and spontaneous preterm delivery. Am J Reprod Immunol 2013; 70: 162–175., , , , , , , , , , , , , .
- Issue published online: 10 JUL 2013
- Article first published online: 10 JUL 2013
- Manuscript Accepted: 30 APR 2013
- Manuscript Received: 17 APR 2013
- 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). Grant Number: HSN275201300006C
- Flow cytometry;
- preterm birth;
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 24–28 weeks 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.
(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 34 weeks (adjusted OR = 2.88; P = 0.001) and after 34 weeks 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 34 weeks 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.
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.