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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1234-1239. Prepublished online as a Blood First Edition Paper on October 24, 2007; DOI 10.1182/blood-2007-09-112680. This Article Full Text (PDF) All Versions of this Article: blood-2007-09-112680v1 111/3/1234    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Peterson, J. A Articles by Aster, R. H Search for Related Content PubMed PubMed Citation Articles by Peterson, J. A Articles by Aster, R. H Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 18, 2007 Accepted October 18, 2007 Fine specificity of drug-dependent antibodies reactive with a restricted domain of platelet GPIIIA Julie A Peterson*, Tamara N Nelson, Adam J Kanack, and Richard H Aster Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI, United States Departments of Medicine and Pathology, Medical College of Wisconsin, MIlwaukee, WI, United States * Corresponding author; email: julie.peterson{at}bcw.edu. Drug-induced immune thrombocytopenia is caused by drug-dependent antibodies (DDAbs) that bind tightly to platelet glycoproteins only when drug is present. How drugs mediate this interaction is not yet resolved. Several studies indicate that sites recognized by DDAbs tend to cluster in specific structural domains, suggesting they may recognize a limited number of distinct epitopes. To address this issue, we characterized the binding sites for 16 quinine-dependent antibodies thought on the basis of preliminary studies to be possibly specific for a single epitope on GPIIIa. Fourteen of the antibodies reacted with a 29kD GPIIIa fragment comprising only the GPIIIa hybrid and PSI homology domains. However, studies with mutant GPIIIa and the blocking monoclonal antibody AP3 showed that the 14 DDAbs recognize at least 6 and possibly more distinct, but overlapping structures involving GPIIIa residues 50-66. The findings suggest that even antibodies specific for restricted domains on a target glycoprotein may each have a slightly different fine specificity, i.e., "unique" epitopes recognized by DDAbs may be rare or non-existent. The observations are consistent with a recently proposed model in which drug reacts non-covalently with both target protein and antibody to promote binding of an otherwise non-reactive immunoglobulin. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. H. Aster Molecular mimicry and immune thrombocytopenia Blood, April 23, 2009; 113(17): 3887 - 3888. [Full Text] [PDF]

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