科研之友
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摘要
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening disease in which intracranial hemorrhage (ICH) is the major risk. Although thrombocytopenia, which is caused by maternal antibodies against in integrin and occasionally by maternal antibodies against other platelet antigens, such as glycoprotein GPIb alpha, has long been assumed to be the cause of bleeding, the mechanism of ICH has not been adequately explored. Utilizing murine models of FNAIT and a high-frequency ultrasound imaging system, we found that ICH only occurred in fetuses and neonates with anti-beta 3 integrin-mediated, but not anti-GPIb alpha-mediated, FNAIT, despite similar thrombocytopenia in both groups. Only anti-beta 3 integrin-mediated FNAIT reduced brain and retina vessel density, impaired angiogenic signaling, and increased endothelial cell apoptosis, all of which were abrogated by maternal administration of intravenous immunoglobulin (IVIG). ICH and impairment of retinal angiogenesis were further reproduced in neonates by injection of anti-beta 3 integrin, but not anti-GPIb alpha antisera. Utilizing cultured human endothelial cells, we found that cell proliferation, network formation, and Ala phosphorylation were inhibited only by murine anti-beta 3 integrin antisera and human anti-HPA-1a IgG purified from mothers with FNAIT children. Our data suggest that fetal hemostasis is distinct and that impairment of angiogenesis rather than thrombocytopenia likely causes FNAIT-associated ICH. Additionally, our results indicate that maternal IVIG therapy can effectively prevent this devastating disorder.
- 出版日期2015-4
- 单位河北医科大学
