Journal article

Human leukocyte antigen class I-restricted activation of CD8( ) T cells provides the immunogenetic basis of a systemic drug hypersensitivity

Diana Chessman, Lyudmila Kostenko, Tessa Lethborg, Anthony W Purcell, Nicholas A Williamson, Zhenjun Chen, Lars Kjer-Nielsen, Nicole A Mifsud, Brian D Tait, Rhonda Holdsworth, Coral Ann Almeida, David Nolan, Whitney A Macdonalds, Julia K Archbold, Anthony D Kellerher, Debbie Marriott, Simon Mallal, Mandvi Bharadwaj, Jamie Rossjohn, James McCluskey

IMMUNITY | CELL PRESS | Published : 2008


The basis for strong immunogenetic associations between particular human leukocyte antigen (HLA) class I allotypes and inflammatory conditions like Behçet's disease (HLA-B51) and ankylosing spondylitis (HLA-B27) remain mysterious. Recently, however, even stronger HLA associations are reported in drug hypersensitivities to the reverse-transcriptase inhibitor abacavir (HLA-B57), the gout prophylactic allopurinol (HLA-B58), and the antiepileptic carbamazepine (HLA-B*1502), providing a defined disease trigger and suggesting a general mechanism for these associations. We show that systemic reactions to abacavir were driven by drug-specific activation of cytokine-producing, cytotoxic CD8+ T cells...

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