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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Enhanced antigenicity leads to altered immunogenicity in sulfamethoxazole-hypersensitive patients with cystic fibrosis
Journal of Allergy and Clinical Immunology, Volume 127, No. 6, Year 2011
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Description
Background: Exposure of patients with cystic fibrosis to sulfonamides is associated with a high incidence of hypersensitivity reactions. Objective: To compare mechanisms of antigen presentation and characterize the phenotype and function of T cells from sulfamethoxazole-hypersensitive patients with and without cystic fibrosis. Methods: T cells were cloned from 6 patients and characterized in terms of phenotype and function. Antigen specificity and mechanisms of antigen presentation to specific clones were then explored. Antigen-presenting cell metabolism of sulfamethoxazole was quantified by ELISA. The involvement of metabolism in antigen presentation was evaluated by using enzyme inhibitors. Results: Enzyme inhibitable sulfamethoxazole-derived protein adducts were detected in antigen-presenting cells from patients with and without cystic fibrosis. A significantly higher quantity of adducts were detected with cells from patients with cystic fibrosis. Over 500 CD4+ or CD8 + T-cell clones were generated and shown to proliferate and kill target cells. Three patterns of MHC-restricted reactivity (sulfamethoxazole- responsive, sulfamethoxazole metabolite-responsive, and cross-reactive) were observed with clones from patients without cystic fibrosis. From patients with cystic fibrosis, sulfamethoxazole metabolite-responsive and cross-reactive, but not sulfamethoxazole-responsive, clones were observed. The response of the cross-reactive clones to sulfamethoxazole was dependent on adduct formation and was blocked by glutathione and enzyme inhibitors. Antigen-stimulated clones from patients with cystic fibrosis secreted higher levels of IFN-γ, IL-6, and IL-10, but lower levels of IL-17. Conclusion: Sulfamethoxazole metabolism and protein adduct formation is critical for the stimulation of T cells from patients with cystic fibrosis. T cells from patients with cystic fibrosis secrete high levels of IFN-γ, IL-6, and IL-10. © 2011 American Academy of Allergy, Asthma & Immunology.
Authors & Co-Authors
Elsheikh, Ayman
United Kingdom, Liverpool
University of Liverpool
Egypt, Tanta
Tanta University
Castrejon, Luis
United Kingdom, Liverpool
University of Liverpool
Lavergne, Sidonie N.
United Kingdom, Liverpool
University of Liverpool
United States, Urbana
University of Illinois Urbana-champaign
Whitaker, Paul
United Kingdom, Leeds
St James's University Hospital
Monshi, Manal
United Kingdom, Liverpool
University of Liverpool
Saudi Arabia, Riyadh
King Fahad Medical City
Callan, Hayley
United Kingdom, Liverpool
University of Liverpool
El-Ghaiesh, Sabah
United Kingdom, Liverpool
University of Liverpool
Egypt, Tanta
Tanta University
Farrell, John
United Kingdom, Liverpool
University of Liverpool
Pichler, Werner J.
Switzerland, Bern
University Hospital Bern
Peckham, Daniel Gavin
United Kingdom, Leeds
St James's University Hospital
Park, B. Kevin
United Kingdom, Liverpool
University of Liverpool
Naisbitt, Dean John
United Kingdom, Liverpool
University of Liverpool
Statistics
Citations: 14
Authors: 12
Affiliations: 6
Identifiers
Doi:
10.1016/j.jaci.2010.12.1119
ISSN:
00916749
e-ISSN:
10976825
Study Design
Cohort Study