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

作者：Lee JoonHo; Romero Roberto; Xu Yi; Miranda Jezid; Yoo Wonsuk; Chaemsaithong Piya; Kusanovic Juan Pedro; Chaiworapongsa Tinnakorn; Tarca Adi L; Korzeniewski Steven J; Hassan Sonia S; Than Nandor Gabor; Yoon Bo Hyun; Kim Chong Jai^*

来源：American Journal of Reproductive Immunology, 2013, 70(2): 162-175.

DOI：10.1111/aji.12141

• Flow cytometry
• preterm birth
• rejection
• transplantation

Problem %26lt;br%26gt;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. %26lt;br%26gt;Methods of study %26lt;br%26gt;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. %26lt;br%26gt;Results %26lt;br%26gt;(i) Patients with spontaneous preterm delivery were more likely to exhibit HLA class I (adjusted OR=2.54, P%26lt;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%26lt;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%26lt;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. %26lt;br%26gt;Conclusion %26lt;br%26gt;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.

• 出版日期2013-8