Document Detail


Cytokine profiling in abacavir hypersensitivity patients.
MedLine Citation:
PMID:  18505179     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Coral-Ann M Almeida; Annalise M Martin; David Nolan; Andrew Lucas; Paul U Cameron; Ian James; Elizabeth Phillips; Simon Mallal
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Antiviral therapy     Volume:  13     ISSN:  1359-6535     ISO Abbreviation:  Antivir. Ther. (Lond.)     Publication Date:  2008  
Date Detail:
Created Date:  2008-05-28     Completed Date:  2008-06-30     Revised Date:  2013-05-24    
Medline Journal Info:
Nlm Unique ID:  9815705     Medline TA:  Antivir Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  281-8     Citation Subset:  IM    
Affiliation:
Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Australia.
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MeSH Terms
Descriptor/Qualifier:
Anti-HIV Agents / adverse effects*
Cells, Cultured
Cytokines / metabolism*
Dideoxynucleosides / adverse effects*
Drug Hypersensitivity* / etiology,  genetics,  immunology,  physiopathology
HIV Infections / drug therapy,  virology
HLA-B Antigens / genetics
Humans
Interferon-gamma / biosynthesis
Leukocytes, Mononuclear / immunology
Reverse Transcriptase Inhibitors / adverse effects*
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Cytokines; 0/Dideoxynucleosides; 0/HLA-B Antigens; 0/HLA-B*57:01 antigen; 0/Reverse Transcriptase Inhibitors; 82115-62-6/Interferon-gamma; WR2TIP26VS/abacavir

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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