Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1993-10-25
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1767-75
pubmed:dateRevised
2007-11-14
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
pubmed:year
1993
pubmed:articleTitle
A recombinant factor VIII A2 domain polypeptide quantitatively neutralizes human inhibitor antibodies that bind to A2.
pubmed:affiliation
Holland Laboratory, American Red Cross, Rockville, MD 20855.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.