Department of Clinical Immunology and Transfusion Medicine, University and Regional Laboratories Region Skåne, Lund, Sweden.
Department of Laboratory Medicine, Diagnostic Clinic, University Hospital of North Norway, Tromsø, Norway.
Blood Adv. 2019 Apr 9;3(7):945-951. doi: 10.1182/bloodadvances.2019032227.
HLA-DRB301:01 is a predisposing factor for human platelet antigen 1a (HPA-1a) immunization, which is responsible for most cases of fetal and neonatal alloimmune thrombocytopenia. The aim of this study was to investigate if the HLA-DRB301:01 allele imposes a dose-dependent effect on anti-HPA-1a levels and neonatal platelet counts. One hundred and thirty HPA-1a-immunized women were divided into 3 groups: HLA-DRB301:01 negative, HLA-DRB301:01 hemizygous or heterozygous, and HLA-DRB301:01 homozygous. The dose of the HLA-DRB301:01 allele was determined by sequencing exon 2 of the HLA-DRB3 gene followed by HLA-DRB3 and HLA-DRB1 typing of selected samples. Anti-HPA-1a levels at time of delivery and neonatal platelet counts were compared among groups. There was a significant dose-dependent effect of the HLA-DRB301:01 allele on anti-HPA-1a levels (global value [ ] = .0032). Median (range) anti-HPA-1a levels were 1.5 IU/mL (0.0-19.0 IU/mL), 21.1 IU/mL (0.0-1967 IU/mL), and 43.7 IU/mL (1.0-980 IU/mL) in women with 0, 1, and 2 copies of the HLA-DRB301:01 allele, respectively. There was also a significant, but opposite, dose-dependent effect of the mother's HLA-DRB301:01 allele on the platelet count of the newborn ( = .0155). Median (range) neonatal platelet counts were 241 × 10/L (59 × 10/L to 393 × 10/L), 107 × 10/L (4 × 10/L to 387 × 10/L) and 32 × 10/L (4 × 10/L to 352 × 10/L) for newborns of mothers with 0, 1, and 2 copies of the HLA-DRB301:01 allele, respectively. Thus, the HLA-DRB3*01:01 allele exhibits a dose-dependent impact on maternal anti-HPA-1a levels in HPA-1a-immunized women.
HLA-DRB301:01 是人类血小板抗原 1a（HPA-1a）免疫的易感因素，该抗原负责大多数胎儿和新生儿同种免疫性血小板减少症的发病。本研究旨在探讨 HLA-DRB301:01 等位基因是否对抗-HPA-1a 水平和新生儿血小板计数产生剂量依赖性影响。将 130 名 HPA-1a 免疫的女性分为 3 组：HLA-DRB301:01 阴性、HLA-DRB301:01 半合子或杂合子和 HLA-DRB301:01 纯合子。通过对 HLA-DRB3 基因外显子 2 进行测序，然后对选定样本进行 HLA-DRB3 和 HLA-DRB1 分型，确定 HLA-DRB301:01 等位基因的剂量。比较各组分娩时的抗-HPA-1a 水平和新生儿血小板计数。HLA-DRB301:01 等位基因对抗-HPA-1a 水平具有显著的剂量依赖性影响（全局 值[ ] =.0032）。中位（范围）抗-HPA-1a 水平分别为 1.5 IU/mL（0.0-19.0 IU/mL）、21.1 IU/mL（0.0-1967 IU/mL）和 43.7 IU/mL（1.0-980 IU/mL），分别为携带 0、1 和 2 个 HLA-DRB301:01 等位基因的女性。母亲 HLA-DRB301:01 等位基因对新生儿血小板计数也有显著的、但相反的剂量依赖性影响（ =.0155）。新生儿血小板计数的中位数（范围）分别为 241×10/L（59×10/L 至 393×10/L）、107×10/L（4×10/L 至 387×10/L）和 32×10/L（4×10/L 至 352×10/L），分别为携带 0、1 和 2 个 HLA-DRB301:01 等位基因的母亲所生新生儿的血小板计数。因此，HLA-DRB3*01:01 等位基因在 HPA-1a 免疫的女性中对母体抗-HPA-1a 水平具有剂量依赖性影响。
