Cytokine profiling in abacavir hypersensitivity patients.
Antivir Ther
; 13(2): 281-8, 2008.
Article
em En
| MEDLINE
| ID: mdl-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.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Didesoxinucleosídeos
/
Citocinas
/
Inibidores da Transcriptase Reversa
/
Fármacos Anti-HIV
/
Hipersensibilidade a Drogas
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article