Cytokine profiling in abacavir hypersensitivity patients

Coral Ann M. Almeida, Annalise M. Martin, David Nolan, Andrew Lucas, Paul U. Cameron, Ian James, Elizabeth Phillips, Simon Mallal

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Background: Abacavir hypersensitivity in genetically susceptible individuals implicates an abacavir-specific T-cell response to either the parent drug or a metabolite generated in vivo. We have analysed the cytokine profile in antigen-presenting cells and the T-lymphocytes that are involved in the pathological immune response to abacavir. Methods: In this study, we compared abacavir-specific cytokine responses in cultured peripheral blood mononuclear cells (PBMCs) from HIV-infected abacavir hypersensitive, tolerant and naive individuals. Cells were cultured in the presence or absence of abacavir. Cytokine expression was determined by microarray analysis, enzyme-linked immunosorbent assays and flow cytometry. Results: We demonstrated using in vitro models of immune activation that the production of interferon-γ was specifically induced by abacavir treatment in PBMCs obtained from hypersensitive patients carrying the HLA-B*5701 allele (median 123.86 compared with -30.83 for tolerant controls, P=0.001). Conclusion: These results provide further insight into the immunological and metabolic basis of abacavir hypersensitivity syndrome. In vitro assays could assist in the identification of susceptible loci by providing a surrogate marker for the hypersensitivity reaction. Such a marker could be studied in unexposed individuals to shed further light on the immunopathogenesis of the abacavir hypersensitivity syndrome.

Original languageEnglish
Pages (from-to)281-288
Number of pages8
JournalAntiviral Therapy
Volume13
Issue number2
Publication statusPublished - 2008
Externally publishedYes

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