检测孕妇血液中的抗 HLA 抗体，以识别有抗体介导的母体抗胎儿排斥和自发性早产风险的患者。
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.
机构信息
Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, USA.
出版信息
Am J Reprod Immunol. 2013 Aug;70(2):162-75. doi: 10.1111/aji.12141.
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 24-28 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.
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 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.
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.
问题
母体对胎儿的排斥是自发性早产的一种疾病机制。本研究的目的是确定在妊娠中期是否存在人类白细胞抗原（HLA）面板反应性抗体（PRA）会增加自发性早产的风险。
方法
这项纵向病例对照研究纳入了自发性早产（n=310）和正常足月妊娠（n=620）的孕妇，根据母亲年龄和孕次进行匹配。在妊娠 14-16、16-20、20-24 和 24-28 周时采集孕妇血浆样本，使用流式细胞术分析 HLA Ⅰ类和Ⅱ类 PRA 阳性。对于 HLA PRA 阳性的部分患者，确定胎儿 HLA 基因型和母体 HLA 同种异体抗体表位。
结果
（i）与足月分娩的患者相比，自发性早产患者更有可能出现 HLA Ⅰ类（调整后的 OR=2.54，P<0.0001）和Ⅱ类（调整后的 OR=1.98，P=0.002）PRA 阳性；（ii）28-34 周（调整后的 OR=2.88；P=0.001）和 34 周后（调整后的 OR=2.53；P<0.0001）自发性早产患者的 HLA Ⅰ类 PRA 阳性率高于足月分娩的患者；（iii）34 周后自发性早产患者的 HLA Ⅱ类 PRA 阳性率高于足月分娩的患者（调整后的 OR=2.04；P=0.002）；（iv）与初产妇相比，多产妇 HLA Ⅰ类 PRA 阳性的风险更高（调整后的 OR=0.097，P<0.0001，初产妇）；（v）初产妇随着妊娠周数的增加，HLA Ⅰ类 PRA 阳性率更高（P=0.001）；（vi）78%的胎儿进行基因分型的患者存在针对胎儿 HLA Ⅰ类抗原的同种抗体。
结论
妊娠中期 HLA Ⅰ类或Ⅱ类 PRA 阳性的孕妇发生自发性早产的风险增加，原因是抗体介导的母体对胎儿的排斥。
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