OBJECTIVE: Anti-interferon-gamma (IFN-gamma) autoantibodies (anti-IFN-gamma Abs) have been increasingly recognized as an important cause of disseminated nontuberculous mycobacterial (DNTM) infection, and identification of this immunodeficiency impacts clinical management. However, the protean disease manifestations and inaccessibility to diagnostic tests in clinical settings hamper its early diagnosis. Here, we sought to determine whether QuantiFERON-TB Gold In-tube (QFT-GIT), a commercialized IFN-gamma release assay, could be used to screen for neutralizing anti-IFN-gamma Abs among previously healthy adults with DNTM infection. METHODS: HIV-uninfected patients with DNTM infection were prospectively enrolled for the QFT-GIT assays. We measured their plasma concentration of anti-IFN-gamma Abs and their neutralizing capacity through enzyme-linked immunosorbent assay and flow cytometry. We then analyzed the correlation between QFT-GIT results and the presence of neutralizing anti-IFN-gamma Abs among patients with and without previously recognized immunosuppression, respectively. RESULTS: Irrespective of the autoantibody concentration or disease activity, all patients with neutralizing anti-IFN-gamma Abs (100%, 30/30) had indeterminate QFT-GIT results due to extremely low or undetectable IFN-gamma levels in the mitogen tubes. None of the four DNTM patients who were previously healthy and tested negative of anti-IFN-gamma Abs had an indeterminate QFT-GIT result, and their IFN-gamma levels in the mitogen tube were significantly higher than those of the patients with anti-IFN-gamma Abs (8.28 IU/mL vs. 0.05 IU/mL, P = 0.001). CONCLUSION: An indeterminate QFT-GIT result due to undetectable or extremely low IFN-gamma level in the mitogen tube suggests the presence of neutralizing anti-IFN-gamma Abs in a previously healthy patient with DNTM infection.
Date:
2018-02
Relation:
Clinical Microbiology and Infection. 2018 Feb;24(2):159-165.
