Clinical significance of interferon-γ neutralizing autoantibodies against disseminated nontuberculous mycobacterial disease

Abstract

Background

Interferon-γ neutralizing autoantibodies (nIFNγ-autoAb) are reported in patients with disseminated nontuberculous mycobacteria (NTM) infection and may function by increasing the infection risk. Notwithstanding, the prevalence of nIFNγ-autoAb as well as the clinical presentation, diagnosis, and natural history, of disseminated NTM infection in these patients is poorly understood.

Methods

In this retrospective observational study, data and sera for 331 Japanese subjects with mycobacterial infection were collected and analyzed. IFNγ-autoAb titers in sera were quantified using an enzyme-linked immunosorbent assay; neutralizing capacity was evaluated via flow cytometry.

Results

Disseminated NTM was identified in 50 HIV-negative patients. Of these, 30 of 37 (81%) immunocompetent patients had an increased nIFNγ-autoAb titer while only 1 of 13 (7.7%) immunodeficient patients had an increased nIFNγ-autoAb titer (p<0.0001, chi squared). Presenting symptoms were non-specific and NTM infection was not included in the differential diagnosis in most cases. All patients with disseminated NTM and increased a serum nIFNγ-autoAb level received prolonged antimicrobial therapy. In 6 cases when antibiotic treatment was discontinued, NTM infection recurred and required resumption of antibiotic therapy for infection control. The mortality rate was 3.2% in disseminated NTM patients with nIFNγ-autoAb and 21% in those without.

Conclusions

nIFNγ-autoAb were present in most patients with disseminated NTM infection without a diagnosis of clinical immunodeficiency. Diagnosis of disseminated NTM requires a high degree of suspicion and can be improved by measuring serum nIFNγ-autoAb titer. Long-term antibiotic therapy helps prevent recrudescent NTM infection.