Depressed Gamma Interferon Responses and Treatment Outcomes in Tuberculosis Patients: a Prospective Cohort Study

• Published in: Journal of clinical microbiology 2018-10, Vol.56 (10)
• Main Authors: Feng, Jia-Yih, Pan, Sheng-Wei, Huang, Shiang-Fen, Chen, Ying-Ying, Lin, Yung-Yang, Su, Wei-Juin
• Format: Article
• Language: English
• Subjects: Mycobacteriology and Aerobic Actinomycetes
• ISSN: 0095-1137; 1098-660X
• DOI: 10.1128/JCM.00664-18

Immunosuppression induced by is important in the pathogenesis of active tuberculosis (TB). However, the impact of depressed TB-specific and non-TB-specific gamma interferon (IFN-γ) response on the treatment outcomes of TB patients remains uncertain. In this prospective cohort study, culture- or pathology-proven active TB patients were enrolled and QuantiFERON-TB Gold In-Tube (QFT-GIT) assays were performed before the initiation of anti-TB treatment. TB-specific IFN-γ responses (TB antigen tube subtracted from the nil tube) and non-TB-specific IFN-γ responses (mitogen tube subtracted from the nil tube) were measured and associated with treatment outcomes, including 2-month culture conversion and on-treatment mortality. A total of 212 active TB patients were included in the analysis. We observed a close correlation between decreased lymphocyte count and lower non-TB-specific IFN-γ responses but not TB-specific IFN-γ responses. Patients with lower non-TB-specific IFN-γ responses had lower 2-month culture conversion rate (71.1% versus 84.7%, respectively; = 0.033) and higher on-treatment mortality (22.6% versus 5.7%, respectively; = 0.001) than those with higher non-TB-specific IFN-γ responses. In multivariate analysis, depressed non-TB-specific IFN-γ response was an independent factor associated with 2-month sputum culture nonconversion (odds ratio [OR], 2.49; 95% CI [95% confidence interval], 1.05 to 5.90) and on-treatment mortality (hazard ratio [HR], 2.76; 95% CI, 1.15 to 6.62). In contrast, depressed TB-specific IFN-γ responses were significantly associated with higher on-treatment mortality in univariate analysis but not in multivariate analysis. Our findings suggest that depressed non-TB-specific responses, but not TB-specific IFN-γ responses, as measured by QFT-GIT before the initiation of anti-TB treatment, were significantly associated with worse treatment outcomes in TB patients.