Cytokine profiling in abacavir hypersensitivity patients.

Almeida CA, Martin AM, Nolan D, Lucas A, Cameron PU, James I, Phillips E, Mallal S
Antivir Ther. 2008 13 (2): 281-8

PMID: 18505179

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.

MeSH Terms (11)

Anti-HIV Agents Cells, Cultured Cytokines Dideoxynucleosides Drug Hypersensitivity HIV Infections HLA-B Antigens Humans Interferon-gamma Leukocytes, Mononuclear Reverse Transcriptase Inhibitors

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