title: No Evidence for Drug-Specific Activation of Circulating T Cells from Patients with HLA-DRB1*07:01-Restricted Lapatinib-Induced Liver Injury.
abstract: It is hypothesized that lapatinib-induced liver injury is caused by HLA-mediated antigen presentation to CD4 positive T cells. However, analysis of PBMC and cloned T-cells from patients with HLA-DRB1*07:01-restricted lapatinib-induced liver injury revealed no evidence for drug-specific activation. T cells were exposed to lapatinib, the M11 aldehyde, and quinone imine [oxidized form of hydroquinone amine M1] metabolites. Reactivity of the quinone imine was confirmed by mass spectrometry.
authors.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool , Sherrington Building, Ashton Street, Liverpool L69 3GE, England.
authors.forename: Lee
authors.initials: L
authors.lastname: Faulkner
authors.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool , Sherrington Building, Ashton Street, Liverpool L69 3GE, England.
authors.forename: Xiaoli
authors.identifier: 0000-0002-7774-2075
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool , Sherrington Building, Ashton Street, Liverpool L69 3GE, England.
authors.forename: Dean J
authors.identifier: 0000-0003-4107-7832
authors.initials: DJ
authors.lastname: Naisbitt
authors.affiliation: Target Sciences, GlaxoSmithKline Research & Development , Gunnels Wood Road, Stevenage SG1 2NY, U.K.
authors.forename: Colin F
authors.initials: CF
authors.lastname: Spraggs
authors.affiliation: Department of Molecular and Clinical Pharmacology, University of Liverpool , Sherrington Building, Ashton Street, Liverpool L69 3GE, England.
authors.forename: B Kevin
authors.initials: BK
authors.lastname: Park
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000276:immunology*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D000077341:Lapatinib; D008213:Lymphocyte Activation / Q000187:drug effects*; D011799:Quinazolines / Q000009:adverse effects* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D059811:HLA-DRB1 Chains; D011799:Quinazolines; D000077341:Lapatinib