Advanced

A novel murine model of fetal and neonatal alloimmune thrombocytopenia : Response to intravenous IgG therapy

Ni, Heyu ; Chen, Pingguo ; Spring, Christopher M. ; Sayeh, Ebrahim ; Semple, John W. LU ; Lazarus, Alan H. ; Hynes, Richard O. and Freedman, John (2006) In Blood 107(7). p.2976-2983
Abstract

Fetal and neonatal alloimmune thrombocytopenia (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 (β3 integrin). Here we have established a novel animal model of FNAITP using β3 integrin-deficient (β3-/-) mice. We demonstrated first that these mice are immunoresponsive to β3 integrin; β3-/- mice transfused with wild-type platelets generated specific anti-β3 antibodies which were able to induce thrombocytopenia in wild-type mice. Subsequently, β3-/-... (More)

Fetal and neonatal alloimmune thrombocytopenia (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 (β3 integrin). Here we have established a novel animal model of FNAITP using β3 integrin-deficient (β3-/-) mice. We demonstrated first that these mice are immunoresponsive to β3 integrin; β3-/- mice transfused with wild-type platelets generated specific anti-β3 antibodies which were able to induce thrombocytopenia in wild-type mice. Subsequently, β3-/- 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-β3 antibodies 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.

(Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
107
issue
7
pages
2976 - 2983
publisher
American Society of Hematology
external identifiers
  • scopus:33645531319
  • pmid:16317099
ISSN
0006-4971
DOI
10.1182/blood-2005-06-2562
language
English
LU publication?
no
id
633b498e-719c-46eb-b510-625f744743b8
date added to LUP
2019-12-03 10:19:59
date last changed
2020-02-12 10:18:02
@article{633b498e-719c-46eb-b510-625f744743b8,
  abstract     = {<p>Fetal and neonatal alloimmune thrombocytopenia (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 (β3 integrin). Here we have established a novel animal model of FNAITP using β<sub>3</sub> integrin-deficient (β<sub>3</sub><sup>-/-</sup>) mice. We demonstrated first that these mice are immunoresponsive to β<sub>3</sub> integrin; β<sub>3</sub><sup>-/-</sup> mice transfused with wild-type platelets generated specific anti-β<sub>3</sub> antibodies which were able to induce thrombocytopenia in wild-type mice. Subsequently, β<sub>3</sub><sup>-/-</sup> 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-β<sub>3</sub> antibodies 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.</p>},
  author       = {Ni, Heyu and Chen, Pingguo and Spring, Christopher M. and Sayeh, Ebrahim and Semple, John W. and Lazarus, Alan H. and Hynes, Richard O. and Freedman, John},
  issn         = {0006-4971},
  language     = {eng},
  month        = {04},
  number       = {7},
  pages        = {2976--2983},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {A novel murine model of fetal and neonatal alloimmune thrombocytopenia : Response to intravenous IgG therapy},
  url          = {http://dx.doi.org/10.1182/blood-2005-06-2562},
  doi          = {10.1182/blood-2005-06-2562},
  volume       = {107},
  year         = {2006},
}