title: Cytokine profiling in abacavir hypersensitivity patients.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Australia.
authors.forename: Coral-Ann M
authors.initials: CA
authors.lastname: Almeida
authors.forename: Annalise M
authors.initials: AM
authors.lastname: Martin
authors.forename: David
authors.initials: D
authors.lastname: Nolan
authors.forename: Andrew
authors.initials: A
authors.lastname: Lucas
authors.forename: Paul U
authors.initials: PU
authors.lastname: Cameron
authors.forename: Ian
authors.initials: I
authors.lastname: James
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Phillips
authors.forename: Simon
authors.initials: S
authors.lastname: Mallal
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D015224:Dideoxynucleosides / Q000009:adverse effects*; D004342:Drug Hypersensitivity / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D016207:Cytokines; D015224:Dideoxynucleosides; D015235:HLA-B Antigens; D007371:Interferon-gamma; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir; C484830:HLA-B*57:01 antigen