Animal model of fetal and neonatal immune thrombocytopenia: role of neonatal Fc receptor in the pathogenesis and therapy

Blood
Pingguo ChenHeyu Ni

Abstract

Fetal and neonatal immune thrombocytopenia (FNIT) is a severe bleeding disorder in which maternal antibodies cross the placenta and destroy fetal/neonatal platelets. It has been demonstrated that the neonatal Fc receptor (FcRn) regulates immunoglobulin G (IgG) homeostasis and plays an important role in transplacental IgG transport. However, the role of FcRn in the pathogenesis and therapy of FNIT has not been studied. Here, we developed an animal model of FNIT using combined β3 integrin-deficient and FcRn-deficient (β3(-/-)FcRn(-/-)) mice. We found that β3(-/-)FcRn(-/-) mice are immunoresponsive to β3(+/+)FcRn(-/-) platelets. The generated antibodies were β3 integrin specific and were maintained at levels that efficiently induced thrombocytopenia in adult β3(+/+)FcRn(-/-) mice. FNIT was observed when immunized β3(-/-)FcRn(+/+) females were bred with β3(+/+)FcRn(+/+) males, while no FNIT occurred in β3(-/-)FcRn(-/-) females bred with β3(+/+)FcRn(-/-) males, suggesting that FcRn is indispensable for the induction of FNIT. We further demonstrated that fetal FcRn was responsible for the transplacental transport of various IgG isotypes. We found that anti-FcRn antibody and intravenous IgG prevented FNIT, and that intravenous IgG ame...Continue Reading

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