Functional neutralization of anti-IFN-γ autoantibody in patients with nontuberculous mycobacteria infection

• Published in: Scientific reports Vol. 9; no. 1; p. 5682
• Main Authors: Krisnawati, Dyah Ika, Liu, Yung-Ching, Lee, Yuarn-Jang, Wang, Yun-Ting, Chen, Chia-Ling, Tseng, Po-Chun, Lin, Chiou-Feng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.04.2019; Nature Publishing Group
• Subjects: 13; 13/1; 13/21; 13/95; 14; 631/250/38; 692/53/2421; 82; Antibodies, Neutralizing - immunology; Antitumor activity; Autoantibodies; Autoantibodies - immunology; Biological activity; Cell Line; Cell Line, Tumor; Chemokines; Colorimetry; Enzyme-linked immunosorbent assay; Epitopes; Humanities and Social Sciences; Humans; Immunodeficiency; Immunomodulation; Immunosurveillance; Infections; Interferon regulatory factor 1; Interferon-gamma - immunology; Jurkat Cells; multidisciplinary; Mycobacterium Infections, Nontuberculous - immunology; Nontuberculous Mycobacteria - immunology; Science; Science (multidisciplinary); Serum levels; Stat1 protein; THP-1 Cells; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-41952-1

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.