Allergic sensitization to pegylated interferon-α results in drug eruptions
| Autor: | Peter Arne Gerber, Albert Zlotnik, S. Kellermann, Dieter Häussinger, Thomas Göbel, Erich Bünemann, Stephan Meller, Ulrike Wiesner, Andreas Erhardt, Peter Hevezi, Bernhard Homey, Andreas Kislat |
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| Rok vydání: | 2015 |
| Předmět: |
Chemokine
Immunology Gene Expression Interferon alpha-2 Lymphocyte Activation Antiviral Agents Polyethylene Glycols Allergic sensitization chemistry.chemical_compound Interferon Pegylated interferon T-Lymphocyte Subsets medicine Immunology and Allergy Humans Skin Skin Tests biology business.industry Ribavirin Immunogenicity Interferon-alpha Hepatitis C Hepatitis C Chronic medicine.disease Recombinant Proteins Drug eruption chemistry Interferon Regulatory Factors biology.protein Cytokines Drug Eruptions business medicine.drug |
| Zdroj: | Allergy. 70(7) |
| ISSN: | 1398-9995 |
| Popis: | Background The introduction of pegylated interferon (PEG-IFN)-α in the treatment of chronic hepatitis C has led to an increase in sustained virological response. Despite reduced immunogenicity of the pegylated form in comparison with native interferon (IFN)-α, a high frequency of adverse cutaneous reactions has been reported with pegylated IFN-α. Here, we aimed to investigate the immunological mechanisms underlying pegylated IFN-α-induced drug eruptions. Methods Hepatitis C patients suffering from drug eruptions in association with administration of pegylated interferons were enrolled in the study (n = 22). Subjects were tested for sensitivity to pegylated IFN-α2a, pegylated IFN-α2b, or ribavirin using intradermal, scratch, and/or patch tests, as well as lymphocyte activation tests (LATs). Skin biopsies obtained from pegylated IFN-α-associated exanthemas, as well as from localized inflammatory skin reactions at pegylated IFN-α injection sites, were analyzed for the expression of relevant chemokines by quantitative real-time PCR and immunohistochemistry. Results A subset of patients suffering from pegylated IFN-α-associated exanthemas displayed positive intradermal tests to PEG-IFNs but not to conventional IFN (11/22). In selected patients, this observation correlated with the presence of pegylated IFN-specific T cells (3/11). Chemokine profiles of inflammatory skin reactions at the injection sites reflected an IFN-α-signature, whereas lesional skin of exanthemas showed induction of TH2-associated chemokines. Conclusions Our results indicate that specific sensitizations are one cause of exanthemas under therapy with PEG-IFNs. Clinical proof-of-concept analyses demonstrate that affected patients may benefit from a switch to conventional, nonpegylated drugs, enabling IFN-α therapy continuation without drug-associated skin eruptions. |
| Databáze: | OpenAIRE |
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