Detection of interferon alpha protein reveals differential levels and cellular sources in disease.
Detection of interferon alpha protein reveals differential levels and cellular sources in disease.
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DOI：
10.1084/jem.20161451
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发表时间：
2017-05-01
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影响因子：
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通讯作者：
Duffy D
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作者：
Rodero MP;Decalf J;Bondet V;Hunt D;Rice GI;Werneke S;McGlasson SL;Alyanakian MA;Bader-Meunier B;Barnerias C;Bellon N;Belot A;Bodemer C;Briggs TA;Desguerre I;Frémond ML;Hully M;van den Maagdenberg AMJM;Melki I;Meyts I;Musset L;Pelzer N;Quartier P;Terwindt GM;Wardlaw J;Wiseman S;Rieux-Laucat F;Rose Y;Neven B;Hertel C;Hayday A;Albert ML;Rozenberg F;Crow YJ;Duffy D
罗德罗等人报告了单基因干扰素病、自身免疫和感染性疾病状态下IFNα蛋白的直接定量，通过数字ELISA和从APECED患者中分离的高亲和力自身抗体的组合，揭示了依赖于基础病理学的差异水平和细胞来源。I型干扰素（IFN）是抗病毒反应的重要介质。这些细胞因子与自身免疫的发病机制有关，最显著的是系统性红斑狼疮（SLE）、糖尿病和皮肌炎，以及单基因I型干扰素病。尽管在健康和疾病中起着重要作用，但I型IFN的直接定量一直具有挑战性。使用单分子阵列（Simoa）数字ELISA技术，我们记录了健康供体、病毒感染以及复杂和单基因干扰素病中IFNα的阿摩尔浓度。IFNα蛋白与功能活性和IFN刺激的基因表达密切相关。高循环IFNα水平与SLE患者的临床严重程度增加相关，IFNα蛋白的细胞来源研究表明了疾病特异性机制。通过数字ELISA测量IFNα阿摩尔浓度将增强我们对IFN生物学的理解，并可能改善与IFN失调相关的病理学的诊断和分层。
Rodero et al. report the direct quantification of IFNα protein in monogenic interferonopathies, autoimmunity, and infectious disease states, made possible by the combination of digital ELISA and high-affinity autoantibodies isolated from APECED patients, revealing differential levels and cellular sources dependent on underlying pathology. Type I interferons (IFNs) are essential mediators of antiviral responses. These cytokines have been implicated in the pathogenesis of autoimmunity, most notably systemic lupus erythematosus (SLE), diabetes mellitus, and dermatomyositis, as well as monogenic type I interferonopathies. Despite a fundamental role in health and disease, the direct quantification of type I IFNs has been challenging. Using single-molecule array (Simoa) digital ELISA technology, we recorded attomolar concentrations of IFNα in healthy donors, viral infection, and complex and monogenic interferonopathies. IFNα protein correlated well with functional activity and IFN-stimulated gene expression. High circulating IFNα levels were associated with increased clinical severity in SLE patients, and a study of the cellular source of IFNα protein indicated disease-specific mechanisms. Measurement of IFNα attomolar concentrations by digital ELISA will enhance our understanding of IFN biology and potentially improve the diagnosis and stratification of pathologies associated with IFN dysregulation.