Detection and quantification of drug-specific T cells in penicillin allergy

• Published in: Allergy 2009-04, Vol.64 (4), p.534-542
• Main Authors: Rozieres, A, Hennino, A, Rodet, K, Gutowski, M.-C, Gunera-Saad, N, Berard, F, Cozon, G, Bienvenu, J, Nicolas, J.-F
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Allergic diseases; Allergies; Amoxicillin - adverse effects; Amoxicillin - immunology; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - immunology; Biological and medical sciences; Child; Child, Preschool; Cross Reactions; delayed hypersensitivity; Dermatology; Diagnostic tests; Drug Hypersensitivity - etiology; Drug Hypersensitivity - immunology; Enzyme-Linked Immunosorbent Assay; enzyme-linked immunospot assay; Exanthema - chemically induced; Exanthema - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunology; Immunopathology; Infant; interferon γ; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; interferons; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Medical sciences; Penicillin; penicillin allergy; Penicillins - adverse effects; Penicillins - immunology; Pharmacology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin allergic diseases. Stinging insect allergies; Skin Diseases - chemically induced; Skin Diseases - immunology; Skin Tests; T cell; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 0105-4538; 1398-9995; 0108-1675
• DOI: 10.1111/j.1398-9995.2008.01674.x

Drug allergic reactions presenting as maculo-papular exanthema (MPE) are mediated by drug-specific T cells. In this study, the frequency of circulating specific T cells was analyzed by interferon-γ (IFN-γ) enzyme-linked immunospot assay in 22 patients with an allergic MPE to amoxicillin (amox). Amox-specific circulating T cells were detected in 20/22 patients with frequencies ranging from 1 : 8000 to 1 : 30 000 circulating leucocytes. No reactivity was observed in 46 control patients, including 15 patients with immunoglobulin E-mediated allergy to amoxicillin, 11 patients with a history of drug-induced MPE but tolerant to amoxicillin and 20 healthy individuals. Furthermore, amox-specific T cells were still detectable several years after the occurrence of the allergic reaction even after strict drug avoidance. Finally, analysis of drug-specific T cells in one patient allergic to ticarcillin (a penicillin antibiotic distinct from amox) revealed the presence of IFN-γ-producing T cells reactive to ticarcillin and several other betalactam antibiotics, suggesting that the IFN-γ ELISPOT assay is able to detect T cell cross-reactivity against chemically related drugs. These findings confirm that drug-induced MPE is associated with the presence of specific T cells in blood and further suggest that the IFN-γ ELISPOT is a sensitive assay which could improve the diagnosis of betalactam allergy.