Details

Autor(en) / Beteiligte

• Krisnawati, Dyah Ika
• Liu, Yung-Ching
• Lee, Yuarn-Jang
• Wang, Yun-Ting
• Chen, Chia-Ling
• Tseng, Po-Chun
• Lin, Chiou-Feng

Titel

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

Ist Teil von

• Scientific reports, 2019-04, Vol.9 (1), p.5682-5682, Article 5682

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.