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Publication : A novel murine model of fetal and neonatal alloimmune thrombocytopenia: response to intravenous IgG therapy.

First Author  Ni H Year  2006
Journal  Blood Volume  107
Issue  7 Pages  2976-83
PubMed ID  16317099 Mgi Jnum  J:131241
Mgi Id  MGI:3773388 Doi  10.1182/blood-2005-06-2562
Citation  Ni H, et al. (2006) A novel murine model of fetal and neonatal alloimmune thrombocytopenia: response to intravenous IgG therapy. Blood 107(7):2976-83
abstractText  Fetal and neonatal alloimmune thrombo cytopenia (FNAITP) is a life-threatening bleeding disorder caused by maternal antibodies directed against fetal platelet antigens. The immunoreactive epitopes in FNAITP are primarily located in the extracellular regions of the platelet glycoprotein IIIa (beta3 integrin). Here we have established a novel animal model of FNAITP using beta3 integrin-deficient (beta3-/-) mice. We demonstrated first that these mice are immunoresponsive to beta3 integrin; beta3-/- mice transfused with wild-type platelets generated specific anti-beta3 antibodies which were able to induce thrombocytopenia in wild-type mice. Subsequently, beta3-/- female mice (both naive and immunized) were bred with wild-type male mice to recapitulate the features of FNAITP. The titer of generated maternal antibodies correlated with the severity of FNAITP. High titer maternal anti-beta3 anti-bodies caused severe fetal thrombocytopenia, intracranial hemorrhage, and even miscarriage. Furthermore, maternal administration of intravenous immunoglobulin G (IgG) ameliorated FNAITP and down-regulated pathogenic antibodies in both the maternal and fetal circulations.
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