title: Phenytoin desensitization monitored by antigen specific T cell response using carboxyfluorescein succinimidyl ester dilution assay.
abstract: We evaluated drug-specific T cell responses in a patient with refractory partial seizures and paroxysmal kinesigenic choreoathetosis successfully treated with clinical desensitization to phenytoin. Drug-induced lymphocyte transformation test before desensitization was negative with a stimulation index of 130%. The frequencies and cytokine-producing phenotypes of phenytoin-specific T cells were examined simultaneously by using a carboxyfluorescein succinimidyl ester (CFSE) dilution assay. Before desensitization, the proportion of CFSElow CD4+ cells in whole CD4+ was 3.09%; 13.6% of CFSElow CD4+ cells were stained with anti-interferon gamma antibody. After desensitization, phenytoin-specific CFSElow CD4+ cells decreased to background level. These results indicate that CFSE dilution assay will be useful for the diagnosis and monitoring of drug hypersensitivity.
authors.affiliation: Department of Pediatrics, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. okumura@med.juntendo.ac.jp
authors.forename: Akihisa
authors.initials: A
authors.lastname: Okumura
authors.forename: Ikuya
authors.initials: I
authors.lastname: Tsuge
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kubota
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kurahashi
authors.forename: Jun
authors.initials: J
authors.lastname: Natsume
authors.forename: Tamiko
authors.initials: T
authors.lastname: Negoro
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D002648:Child; D003888:Desensitization, Immunologic; D004305:Dose-Response Relationship, Drug; D004828:Epilepsies, Partial / Q000188:drug therapy; D005452:Fluoresceins; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D010672:Phenytoin / Q000009:adverse effects*; D013388:Succinimides; D013601:T-Lymphocytes / Q000187:drug effects*
chemical_list: C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D000927:Anticonvulsants; D005452:Fluoresceins; D013388:Succinimides; D010672:Phenytoin