QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.105.083758v1 313/3/1058    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Naisbitt, D. J. Articles by Park, B. K. Search for Related Content PubMed PubMed Citation Articles by Naisbitt, D. J. Articles by Park, B. K. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB PHENINDIONE

TOXICOLOGY

Characterization of the T-Cell Response in a Patient with Phenindione Hypersensitivity

Departments of Pharmacology (D.J.N., J.F., P.J.C., J.E.H., M.P., B.K.P.) and Chemistry (N.G.B.), The University of Liverpool, Liverpool, England

The oral anticoagulant phenindione [2-phenyl-1H-indene-1,3(2H)-dione] is associated with hypersensitivity reactions in 1.5 to 3% of patients, the pathogenesis of which is unclear. We describe a patient who developed a severe hypersensitivity reaction that involved both the skin and lungs. A lymphocyte transformation test showed proliferation of T-cells from the hypersensitive patient, but not from four controls on exposure to phenindione in vitro. Drug-specific T-cell clones were generated and characterized in terms of their phenotype, functionality, and mechanism of antigen presentation. Forty-three human leukocyte antigen class II restricted CD4⁺ T-cell clones were identified. T-cell activation resulted in the secretion of interferon- and interleukin-5. Five of seven clones proliferated with phenindione alone, whereas two clones also proliferated with 2-phenylindene. Certain T-cell clones were also stimulated by R- and S-warfarin; computer modeling revealed that warfarin can adopt a phenindione-like structure. Phenindione was presented to T-cells via two pathways: first, bound directly to major histocompatibility complex and second, bound to a processed peptide. Our data show that CD4⁺ T-cells are involved in the pathophysiology of phenindione hypersensitivity. There may be cross-sensitivity with warfarin in some phenindione hypersensitive patients.

Address correspondence to: Dr. Dean J. Naisbitt, Department of Pharmacology and Therapeutics, Sherrington Building, Ashton Street, The University of Liverpool, P.O. Box 147, Liverpool, L69 3GE, England. E-mail:dnes{at}liv.ac.uk

This article has been cited by other articles:

				B Doshi and S Sarkar Topical administration of chloramphenicol can induce acute hepatitis BMJ, June 12, 2009; 338(jun12_1): b1699 - b1699. [Full Text]