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

Purpose In the past decade, the relationship between naturally occurring interferon-gamma-neutralizing autoantibodies (IFN gamma-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 IFN gamma-Ab, has not yet been fully elucidated. Methods Thirteen Japanese subjects suffering from disseminated NTM (dNTM) infection with IFN gamma-Ab were evaluated. The fluctuation of IFN gamma-Ab titer and the neutralizing capacity against IFN-gamma during the course of the disease were retrospectively analyzed. IFN gamma-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-gamma was maintained by individual sera. Conclusions Despite the improvement in the pathological condition via treatment, the patients' sera maintained neutralizing capacity against IFN-gamma. Antibody titer fluctuated over the course of the disease and exhibited potential as a biomarker for judgment of the disease state.