Division of Neonatology, Department of Pediatrics, Willem-Alexander Children's Hospital, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Center of Clinical Transfusion Research, Sanquin Research, 1066 CX Amsterdam, The Netherlands.
Int J Mol Sci. 2021 Jun 23;22(13):6763. doi: 10.3390/ijms22136763.
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that causes thrombocytopenia and a risk of bleeding in the (unborn) child that result from maternal alloantibodies directed against fetal, paternally inherited, human platelet antigens (HPA). It is hypothesized that these alloantibodies can also bind to the placenta, causing placental damage. This study aims to explore signs of antibody-mediated placental damage in FNAIT. We performed a retrospective study that included pregnant women, their newborns, and placentas. It comprised 23 FNAIT cases, of which nine were newly diagnosed (14 samples) and 14 were antenatally treated with intravenous immune globulins (IVIg) (21 samples), and 20 controls, of which 10 had anti-HLA-class I antibodies. Clinical information was collected from medical records. Placental samples were stained for complement activation markers (C1q, C4d, SC5b-9, and mannose-binding lectin) using immunohistochemistry. Histopathology was examined according to the Amsterdam criteria. A higher degree of C4d deposition was present in the newly diagnosed FNAIT cases (10/14 samples), as compared to the IVIg-treated FNAIT cases (2/21 samples, = 0.002) and anti-HLA-negative controls (3/20 samples, = 0.006). A histopathological examination showed delayed maturation in four (44%) placentas in the newly diagnosed FNAIT cases, five (36%) in the IVIg-treated FNAIT cases, and one in the controls (NS). C4d deposition at the syncytiotrophoblast was present in combination with low-grade villitis of unknown etiology in three newly diagnosed FNAIT cases that were born SGA. We conclude that a higher degree of classical pathway-induced complement activation is present in placentas from pregnancies with untreated FNAIT. This may affect placental function and fetal growth.
胎儿和新生儿同种免疫性血小板减少症（FNAIT）是一种疾病，可导致母亲针对胎儿、父系遗传的人类血小板抗原（HPA）的同种抗体引起胎儿血小板减少症和出血风险。据推测，这些同种抗体也可以与胎盘结合，导致胎盘损伤。本研究旨在探索 FNAIT 中抗体介导的胎盘损伤的迹象。我们进行了一项回顾性研究，纳入了孕妇、新生儿和胎盘。研究包括 23 例 FNAIT 病例，其中 9 例为新诊断（14 例标本），14 例在产前用静脉注射免疫球蛋白（IVIg）治疗（21 例标本），20 例为对照组，其中 10 例有抗 HLA 类 I 抗体。临床信息从病历中收集。使用免疫组织化学法对胎盘样本进行补体激活标志物（C1q、C4d、SC5b-9 和甘露糖结合凝集素）染色。根据阿姆斯特丹标准检查组织病理学。与 IVIg 治疗的 FNAIT 病例（21 例标本中有 2 例， = 0.002）和抗-HLA 阴性对照组（20 例标本中有 3 例， = 0.006）相比，新诊断的 FNAIT 病例中 C4d 沉积程度更高（14 例标本中有 10 例）。组织病理学检查显示，在新诊断的 FNAIT 病例中，有 4 例（44%）胎盘成熟延迟，IVIg 治疗的 FNAIT 病例中 5 例（36%），对照组中 1 例（无显著性差异）。在 3 例出生时为 SGA 的新诊断的 FNAIT 病例中，在合胞体滋养层中存在 C4d 沉积，并伴有病因不明的低级别绒毛膜炎。我们得出结论，未经治疗的 FNAIT 妊娠的胎盘存在更高级别的经典途径诱导的补体激活。这可能会影响胎盘功能和胎儿生长。
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