Incorrect diagnoses in patients with neutralizing anti-interferon-gamma-autoantibodies

Abstract

© 2020 Objectives: Early diagnosis of adult-onset immunodeficiency associated with neutralizing anti-interferon-gamma autoantibodies (anti-IFNγ Abs) remains difficult given the lack of a distinctive phenotype and a routine test. This study aimed to investigate the determinants of incorrect tentative diagnoses and useful clues for early disease recognition. Methods: This study enrolled adult patients who had unexplained opportunistic infections diagnosed at six hospitals and identified those having neutralizing anti-IFNγ Abs (cases). Demographics, medical history, initial presentations and laboratory data, causative pathogens, tentative diagnoses, and treatment were analysed and compared among individuals having neutralizing anti-IFNγ Abs (cases) and those without (controls). Results: Among the 154 patients enrolled, neutralizing anti-IFN-γ Abs were detected in 50 (71%) of 70 patients with disseminated non-tuberculous mycobacterial infection (dNTM) but not in 84 patients without dNTM. The median time from disease onset to the recognition of dNTM associated with neutralizing anti-IFNγ Abs was 1.6 years (range, 0.25–19 years). Incorrect tentative diagnoses resulted in the administration of anti-tuberculosis regimens (60%, 30/50), immunosuppressants (48%, 24/50), and systemic chemotherapy (2%, 10/50) to the 50 cases. Multivariate analysis revealed that case patients were more likely than controls to present with multiple bone lesions (adjusted odds ratio (OR), 27.16; 95% confidence interval (CI), 1.21–609.59) and leukocytosis (adjusted OR, 1.48; 95% CI, 1.12–1.95); however, the controls had a higher rate of mycobacterial bloodstream infection (adjusted OR, 0.05; 95% CI 0.00–0.66). Conclusions: The high rate of incorrect tentative diagnoses led to frequent inappropriate management in patients with neutralizing anti-IFNγ Abs, and highlighted the need for increased awareness among clinicians.