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Serum Anti-interferon-γ Autoantibody Titer as a Potential Biomarker of Disseminated Non-tuberculous Mycobacterial Infection

Abstract

Purpose

In the past decade, the relationship between naturally occurring interferon-γ-neutralizing autoantibodies (IFNγ-Ab) and disseminated non-tuberculous mycobacteria (NTM) infection has been established. Furthermore, immune suppressive therapy aimed at the suppression of antibody production has shown efficacy as a supportive treatment. However, the nature of antibody behavior and antibody titer during the course of this disease, as well as the pathophysiological significance of IFNγ-Ab, has not yet been fully elucidated.

Methods

Thirteen Japanese subjects suffering from disseminated NTM (dNTM) infection with IFNγ-Ab were evaluated. The fluctuation of IFNγ-Ab titer and the neutralizing capacity against IFN-γ during the course of the disease were retrospectively analyzed. IFNγ-Ab titers in the sera were quantified using an enzyme-linked immunosorbent assay; neutralizing capacity was evaluated via flow cytometry.

Results

Serum antibody titers were not constant during the treatment period and varied over the course of the disease. The antibody titer decreased when the disease was improved by anti-mycobacterial treatment (p < 0.01) and increased as the disease progressed (p < 0.05). Even after the antibody titer decreased, the neutralizing capacity against IFN-γ was maintained by individual sera.

Conclusions

Despite the improvement in the pathological condition via treatment, the patients’ sera maintained neutralizing capacity against IFN-γ. Antibody titer fluctuated over the course of the disease and exhibited potential as a biomarker for judgment of the disease state.

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Acknowledgments

We thank all of the attending doctors who referred their patients to our study and all of the participants for their trust. Also, we thank Hiroko Aita for providing excellent technical assistance.

Authorship Contributions

All authors contributed to the conception and design of the study. KY, AA, and KS coordinated the investigation of subjects’ sample analysis. KY and TS performed data analysis and interpretation. TS drafted the manuscript. KY, YT, TK, TH, TK, and TS reviewed the manuscript critically. All authors read and approved the final manuscript.

Conflict of Interest

The authors declare that they have no conflict of interest.

Funding

This work was supported by Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science [25461507 to T.H.] and [19K08956 to T.S.], and by the Research Program on Emerging and Re-emerging Infectious Disease from the Japan Agency for Medical Research and Development.

Author information

Correspondence to Takuro Sakagami.

Ethics declarations

This study was performed with the approval of the Ethics Committee at the School of Medicine, Niigata University (Approval number; 1413), and complied with the Declaration of Helsinki. All subjects provided informed consent.

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Cite this article

Yoshizawa, K., Aoki, A., Shima, K. et al. Serum Anti-interferon-γ Autoantibody Titer as a Potential Biomarker of Disseminated Non-tuberculous Mycobacterial Infection. J Clin Immunol (2020). https://doi.org/10.1007/s10875-020-00762-1

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Keywords

  • Disseminated NTM
  • neutralizing capacity
  • biomarker
  • serum interferon-γ autoantibody titer