Interferon-gamma release assays in patients with Mycobacterium kansasii pulmonary infection: A retrospective survey
Introduction
Interferon-gamma release assays (IGRAs), widely in use to diagnose tuberculosis (TB) infection, are immunologic assays that measure interferon-gamma (IFN-γ) response to TB specific antigens such as early secretory antigenic target-6 (ESAT-6), culture filtrate protein-10 (CFP-10), and TB7.7. IFN-γ stimulated with ESAT-6 and CFP-10 is measured by enzyme-linked immunosorbent assay (ELISA) in QuantiFERON TB-Gold (QFT-G; Cellestis [a Qiagen company], Valencia, CA). Recently, QFT-TB Gold In Tube (QFT-GIT; Cellestis [a Qiagen company], Valencia, CA), which stimulates peripheral lymphocyte with ESAT-6, CFP-10, and TB7.7 became commercially available in many countries. T-SPOT. TB (T-SPOT; Oxford Immunotec Ltd., Abingdon, UK) is the enzyme-linked immunospot (ELISPOT) assay which counts the number of effector T cells that produce INF-γ by stimulation of ESAT-6 and CFP-10. These assays are highly specific and sensitive for TB infection compared with tuberculin skin test (TST).1, 2
Though the prevalence of nontuberculous mycobacterium (NTM) varies according to the geographic region, some epidemiologic data suggest numbers of NTM is increasing in developed countries.3, 4, 5, 6 Pulmonary infection by Mycobacterium kansasii (M. kansasii) is the second most popular NTM infection next to Mycobacterium avium complex in Australia and Japan.3, 6 In addition, M. kansasii is the second most isolated NTM from respiratory samples in some European countries including the United Kingdom, Slovakia, and Poland, accounting for 11%, 36% and 35%, respectively.4 Cavitation in upper pulmonary lobes is a common radiographic feature of M. kansasii pulmonary infection, which resembles pulmonary TB.7, 8 As a result, IGRAs are often performed in undiagnosed M. kansaii cases.
A few species of NTM such as M. kansasii, Mycobacterium marinum, and Mycobacterium szulgai possess CFP-10 and ESAT-6 in their DNA sequence.9, 10 Therefore, IGRAs can be positive in patients infected with these mycobacteria although in practice we had an impression that positive rate seems low in M. kansasii infection. In this retrospective survey we investigated positive rate of IGRAs and factors contributing to positive IGRAs in patients with M. kansasii infection.
Section snippets
Methods
We analyzed M. kansasii pulmonary infection cases which met the diagnostic criteria of NTM by the American Thoracic Society/the Infectious Diseases Society of America (ATS/IDSA)11 diagnosed at National Hospital Organization Tokyo National Hospital between January 2003 and April 2015. M. kansasii was isolated and identified from respiratory specimens (sputum or bronchial washing fluid) in all cases. The cases diagnosed with simultaneous TB and M. kansasii coinfection were excluded. We selected
Statistical analysis
Data are shown as the number of patients with percentage or the average with standard deviation. Fisher's exact test or Pearson's chi-square test was used to compare patients' characteristics. The risk factors for positive IGRAs were evaluated by univariate and multivariate analysis. The candidate factors, including age, previous TB infection, peripheral lymphocyte count, and radiographic features, were chosen for evaluation based on the reported factors affecting IGRAs result in patients with
Patient characteristics and result of IGRAs
Among 157 cases with positive M. kansasii culture, 140 cases met the diagnostic criteria of NTM by ATS/IDSA. 33 cases without IGRAs and 2 cases co-infected with TB were excluded. Among 105 cases analyzed in this study, QFT-G was performed in 59 cases, QFT-GIT in 25 cases, and T-SPOT in 21 cases (Fig. 1).
Clinical characteristics of patients are shown in Table 1. Immunosuppressants including corticosteroids were used in 4 QFT-G cases (3 with interstitial pneumonia and one with bronchial asthma),
Discussion
This is the first study that evaluates the positive rate of three different IGRAs in patients with M. kansasii. The positive rates of IGRAs are 25.9–33.3% while in patients without the previous TB the rates are as low as 18.8–20.0%. The multivariate analysis revealed that the factor contributing to positive IGRAs was only the previous TB, suggesting that T cell response to CFP-10 and ESAT-6 in patients with M. kansasii infection alone might be weak. Previous TB infection potentiated the IFN-γ
Conclusion
The positive rate of IGRAs for TB in patients with M. kansasii was lower than that in patients with active TB, suggesting weak cross-reactivity of TB specific antigens in patients with M. kasasii. Past TB infection significantly affects the IGRA positivity in these patients.
Conflict of interest
None.
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