Source:http://linkedlifedata.com/resource/pubmed/id/20647570
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
18
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| pubmed:dateCreated |
2010-11-5
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| pubmed:abstractText |
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 ?3 integrin-deficient and FcRn-deficient (?3(-/-)FcRn(-/-)) mice. We found that ?3(-/-)FcRn(-/-) mice are immunoresponsive to ?3(+/+)FcRn(-/-) platelets. The generated antibodies were ?3 integrin specific and were maintained at levels that efficiently induced thrombocytopenia in adult ?3(+/+)FcRn(-/-) mice. FNIT was observed when immunized ?3(-/-)FcRn(+/+) females were bred with ?3(+/+)FcRn(+/+) males, while no FNIT occurred in ?3(-/-)FcRn(-/-) females bred with ?3(+/+)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 ameliorated FNIT through both FcRn-dependent and -independent pathways. Our data suggest that targeting FcRn may be a potential therapy for human FNIT as well as other maternal pathogenic antibody-mediated diseases.
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| pubmed:grant | |
| pubmed:commentsCorrections | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Fc receptor, neonatal,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class I,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulins, Intravenous,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin beta3,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Fc
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
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| pubmed:issn |
1528-0020
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
4
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| pubmed:volume |
116
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
3660-8
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| pubmed:meshHeading |
pubmed-meshheading:20647570-Animals,
pubmed-meshheading:20647570-Antibodies,
pubmed-meshheading:20647570-Blood Platelets,
pubmed-meshheading:20647570-Down-Regulation,
pubmed-meshheading:20647570-Female,
pubmed-meshheading:20647570-Fetus,
pubmed-meshheading:20647570-Gene Deletion,
pubmed-meshheading:20647570-Histocompatibility Antigens Class I,
pubmed-meshheading:20647570-Humans,
pubmed-meshheading:20647570-Immunoglobulin G,
pubmed-meshheading:20647570-Immunoglobulins, Intravenous,
pubmed-meshheading:20647570-Integrin beta3,
pubmed-meshheading:20647570-Male,
pubmed-meshheading:20647570-Maternal-Fetal Exchange,
pubmed-meshheading:20647570-Mice,
pubmed-meshheading:20647570-Models, Animal,
pubmed-meshheading:20647570-Placenta,
pubmed-meshheading:20647570-Pregnancy,
pubmed-meshheading:20647570-Protein Transport,
pubmed-meshheading:20647570-Receptors, Fc,
pubmed-meshheading:20647570-Thrombocytopenia, Neonatal Alloimmune
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| pubmed:year |
2010
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| pubmed:articleTitle |
Animal model of fetal and neonatal immune thrombocytopenia: role of neonatal Fc receptor in the pathogenesis and therapy.
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| pubmed:affiliation |
Canadian Blood Services, and Toronto Platelet Immunobiology Group/Department of Laboratory Medicine, Keenan Research Centre, Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Ontario, Canada.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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