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Cytokine profiling in abacavir hypersensitivity patients

Almeida, C.M., Martin, A.M., Nolan, D., Lucas, A., Cameron, P.U., James, I., Phillips, E. and Mallal, S. (2008) Cytokine profiling in abacavir hypersensitivity patients. Antiviral Therapy, 13 (2). pp. 281-288.

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    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-gamma 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.

    Publication Type: Journal Article
    Murdoch Affiliation: Centre for Clinical Immunology and Biomedical Statistics
    Publisher: International Medical Press
    URI: http://researchrepository.murdoch.edu.au/id/eprint/8898
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