Other
21 Authors
- Skogen B,
- Wen XY,
- Vadasz B,
- Chen P,
- Piran S,
- Yang H,
- Zdravic D,
- Freedman J,
- Zhu G,
- Yougbaré I,
- Leong-Poi H,
- Boyd S,
- Li C,
- Tiller H,
- Killie MK,
- Adamson SL,
- Ni H,
- Zhao X,
- Marshall A,
- Tai WS,
- Lang S
| First Author | Yougbaré I | Year | 2015 |
| Journal | J Clin Invest | Volume | 125 |
| Issue | 4 | Pages | 1545-56 |
| PubMed ID | 25774504 | Mgi Jnum | J:222291 |
| Mgi Id | MGI:5644234 | Doi | 10.1172/JCI77820 |
| Citation | Yougbare I, et al. (2015) Maternal anti-platelet beta3 integrins impair angiogenesis and cause intracranial hemorrhage. J Clin Invest 125(4):1545-56 |
| abstractText | 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 beta3 integrin and occasionally by maternal antibodies against other platelet antigens, such as glycoprotein GPIbalpha, 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-beta3 integrin-mediated, but not anti-GPIbalpha-mediated, FNAIT, despite similar thrombocytopenia in both groups. Only anti-beta3 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-beta3 integrin, but not anti-GPIbalpha antisera. Utilizing cultured human endothelial cells, we found that cell proliferation, network formation, and AKT phosphorylation were inhibited only by murine anti-beta3 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. |
