A novel murine model of fetal and neonatal alloimmune thrombocytopenia : Response to intravenous IgG therapy
(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.
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- author
- Ni, Heyu ; Chen, Pingguo ; Spring, Christopher M. ; Sayeh, Ebrahim ; Semple, John W. LU ; Lazarus, Alan H. ; Hynes, Richard O. and Freedman, John
- publishing date
- 2006-04-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Blood
- volume
- 107
- issue
- 7
- pages
- 2976 - 2983
- publisher
- American Society of Hematology
- external identifiers
-
- pmid:16317099
- scopus:33645531319
- 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
- 2024-07-10 07:10:10
@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}}, }