Centre for Vaccines and Immunology (CVI), National Institute for Communicable Diseases (NICD), A Division of the National Health Laboratory Service, Johannesburg, Gauteng, South Africa.
Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, Gauteng, South Africa.
Am J Reprod Immunol. 2020 Aug;84(2):e13264. doi: 10.1111/aji.13264. Epub 2020 Jun 16.
Late in pregnancy, women produce and transfer high amounts of antibodies to the foetus. During gestation, women produce antibodies against human leukocyte antigens (HLA), including antibodies directed at foetal HLA. There is paucity of data on transplacental crossing, specificity and role of HLA antibodies in pregnancy and new-borns.
Using highly sensitive Luminex technology, we measured prevalence of IgG HLA antibodies in 30 mother-infant pairs six weeks post-partum. Additionally, in six pregnant women, we measured HLA antibodies longitudinally and HLA-typed infant DNA to assess whether maternal HLA antibodies were directed at infant specificities.
Overall, 68% of mothers and 44% of infants expressed HLA-I antibodies and 56% of mothers and 52% of infants expressed HLA-II antibodies. Infants shared up to 78% of antibodies with their mothers, suggesting that the remaining antibodies were self-made. Less than 25% of maternal HLA antibodies were detected in infants, possibly due to selection in transplacental crossing. We detected complement-fixing HLA antibodies in mothers and at low levels in infants. In a third of our pregnant subjects, we detected infant-directed HLA antibodies.
Our findings raise the possibility of selection in transplacental crossing of HLA antibodies. As HLA antibodies may act as autoantibodies in the neonate, the mechanism of a selective transfer may give important insights into immune tolerance. Findings also suggest that infants start producing their own HLA antibodies in the first weeks of life, which, together with maternally derived antibodies may impact the infant's immune reaction to HLA proteins.
妊娠晚期，女性会向胎儿大量产生和转移抗体。在妊娠期间，女性会产生针对人类白细胞抗原（HLA）的抗体，包括针对胎儿 HLA 的抗体。关于 HLA 抗体在妊娠和新生儿中的胎盘转移、特异性和作用，数据很少。
我们使用高度敏感的 Luminex 技术，在产后六周测量了 30 对母婴对 IgG HLA 抗体的流行率。此外，在 6 名孕妇中，我们进行了 HLA 抗体的纵向测量，并对婴儿 DNA 进行了 HLA 分型，以评估母体 HLA 抗体是否针对婴儿特异性。
总体而言，68%的母亲和 44%的婴儿表达 HLA-I 抗体，56%的母亲和 52%的婴儿表达 HLA-II 抗体。婴儿与母亲共享高达 78%的抗体，表明其余的抗体是自身产生的。只有不到 25%的母体 HLA 抗体在婴儿中被检测到，这可能是由于胎盘转移中的选择。我们在母亲和婴儿中检测到补体结合的 HLA 抗体，但在婴儿中的水平较低。在三分之一的孕妇中，我们检测到针对婴儿的 HLA 抗体。
我们的发现提出了 HLA 抗体在胎盘转移中选择的可能性。由于 HLA 抗体可能在新生儿中作为自身抗体起作用，因此选择性转移的机制可能为免疫耐受提供重要的见解。研究结果还表明，婴儿在生命的头几周开始产生自己的 HLA 抗体，这些抗体与母体来源的抗体一起，可能会影响婴儿对 HLA 蛋白的免疫反应。
