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. 2016 Dec 19;29(12):2111-2113.
doi: 10.1021/acs.chemrestox.6b00400. Epub 2016 Nov 18.

No Evidence for Drug-Specific Activation of Circulating T Cells from Patients with HLA-DRB1*07:01-Restricted Lapatinib-Induced Liver Injury

Lee Faulkner  1 , Xiaoli Meng  1 , Dean J Naisbitt  1 , Colin F Spraggs  2 , B Kevin Park  1
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No Evidence for Drug-Specific Activation of Circulating T Cells from Patients with HLA-DRB1*07:01-Restricted Lapatinib-Induced Liver Injury

Lee Faulkner et al. Chem Res Toxicol. .

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.

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