Cytokine profiling in abacavir hypersensitivity patients.
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.
Almeida
Coral-Ann M
CA
Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Australia.
Martin
Annalise M
AM
Nolan
David
D
Lucas
Andrew
A
Cameron
Paul U
PU
James
Ian
I
Phillips
Elizabeth
E
Mallal
Simon
S
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
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