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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1993-10-25
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pubmed:abstractText |
Human antibodies that inactivate coagulation factor VIII (fVIII), known as inhibitors, have been shown by immunoblotting or immunoprecipitation assays to bind predominantly to epitopes within the A2 and/or C2 domains of the fVIII protein. Because these assays simply measure antibody binding, a soluble recombinant polypeptide containing the fVIII A2 domain was used to develop a quantitative inhibitor neutralization assay for antibodies that bound only to A2 by immunoblotting assay. Antibodies from six of eight inhibitor plasmas were fully neutralized by A2 (> or = 90%), whereas two were only partially neutralized. These results established the fVIII inhibitor properties of anti-A2 antibodies. In immunoprecipitation assays, five of the eight inhibitors also had significant levels of anti-light-chain antibody. In one case, this light-chain antibody was shown to have inhibitor activity. Because it did not bind to the C2 domain, this antibody appears to define a new inhibitor epitope within the fVIII light chain. Another inhibitor, which was partially neutralized by A2, was not neutralized by the light chain, even though it contained anti-light-chain antibodies by immunoprecipitation assay. Our results show additional complexities of the immune response to fVIII.
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pubmed:grant | |
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, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Factor VIII,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Light Chains,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Sorting Signals,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
82
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1767-75
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:7691236-Animals,
pubmed-meshheading:7691236-Antibodies, Monoclonal,
pubmed-meshheading:7691236-Antibody Specificity,
pubmed-meshheading:7691236-Cell Line,
pubmed-meshheading:7691236-Cloning, Molecular,
pubmed-meshheading:7691236-Epitopes,
pubmed-meshheading:7691236-Factor VIII,
pubmed-meshheading:7691236-Humans,
pubmed-meshheading:7691236-Immunoglobulin G,
pubmed-meshheading:7691236-Immunoglobulin Light Chains,
pubmed-meshheading:7691236-Kinetics,
pubmed-meshheading:7691236-Molecular Sequence Data,
pubmed-meshheading:7691236-Moths,
pubmed-meshheading:7691236-Mutagenesis, Site-Directed,
pubmed-meshheading:7691236-Neutralization Tests,
pubmed-meshheading:7691236-Plasmids,
pubmed-meshheading:7691236-Protein Sorting Signals,
pubmed-meshheading:7691236-Recombinant Proteins,
pubmed-meshheading:7691236-Transfection
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pubmed:year |
1993
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pubmed:articleTitle |
A recombinant factor VIII A2 domain polypeptide quantitatively neutralizes human inhibitor antibodies that bind to A2.
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pubmed:affiliation |
Holland Laboratory, American Red Cross, Rockville, MD 20855.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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