文章基本信息

标题：Functional neutralization of anti-IFN-γ autoantibody in patients with nontuberculous mycobacteria infection
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作者：Dyah Ika Krisnawati ; Yung-Ching Liu ; Yuarn-Jang Lee 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2019
卷号：9
期号：1
页码：1-9
DOI：10.1038/s41598-019-41952-1
出版社：Springer Nature
摘要：Interferon (IFN)-γ is crucial for normal immune surveillance and exhibits immunomodulatory, antimicrobial, and anticancer activity. Patients with nontuberculous mycobacteria (NTM) infection commonly express high levels of anti-IFN-γ autoantibodies (autoAbs) and suffer from recurrent infections due to adult-onset immunodeficiency with defects in IFN-γ immune surveillance. In this study, we developed the methods for determination of anti-IFN-γ autoAbs and then characterized their neutralizing activity in patients with NTM infection. A modified sandwich ELISA-based colorimetric assay followed by immunoblot analysis detected the presence of autoAbs in three out of five serum samples. Serum levels of IFN-γ were decreased. Synthetic peptide binding assay showed variable patterns of epitope recognition in patients positive for anti-IFN-γ autoAbs. Functional tests confirmed that patient serum blocked IFN-γ-activated STAT1 activation and IRF1 transactivation. Furthermore, IFN-γ-regulated inflammation, chemokine production and cytokine production were also blocked. These results provide potentially useful methods to assay anti-IFN-γ autoAbs and to characterize the effects of neutralizing autoAbs on IFN-γ signaling and bioactivity.