聚乙二醇干扰素
医学
免疫学
趋化因子
利巴韦林
聚乙二醇化
敏化
免疫原性
干扰素
丙型肝炎
PEG比率
丙型肝炎病毒
免疫系统
病毒
财务
经济
作者
Stephan Meller,Peter Arne Gerber,Andreas Kislat,Peter Hevezi,Thomas Göbel,Ulrike Wiesner,S Kellermann,Erich Bünemann,Albert Zlotnik,Dieter Häussinger,Andreas Erhardt,Bernhard Homey
出处
期刊:Allergy
[Wiley]
日期:2015-05-06
卷期号:70 (7): 775-783
被引量:16
摘要
Abstract 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 ‐α 2a , pegylated IFN ‐α 2b , or ribavirin using intradermal, scratch, and/or patch tests, as well as lymphocyte activation tests ( LAT s). 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 ‐ IFN s 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 TH 2‐associated chemokines. Conclusions Our results indicate that specific sensitizations are one cause of exanthemas under therapy with PEG ‐ IFN s. 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.
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