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. 2018 Apr;58(4):510-518.
doi: 10.1165/rcmb.2017-0230OC.

Whole-Blood Gene Expression in Pulmonary Nontuberculous Mycobacterial Infection

Steven A Cowman  1   2 , Joseph Jacob  1   3 , David M Hansell  1   3 , Peter Kelleher  1   2 , Robert Wilson  1   2 , William O C Cookson  1 , Miriam F Moffatt  1 , Michael R Loebinger  1   2
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Whole-Blood Gene Expression in Pulmonary Nontuberculous Mycobacterial Infection

Steven A Cowman et al. Am J Respir Cell Mol Biol. 2018 Apr.

Abstract

The factors predisposing toward the development of pulmonary nontuberculous mycobacterial (pNTM) disease and influencing disease progression remain unclear. Impaired immune responses have been reported in individuals with pNTM disease, but data are limited and inconsistent. In this study, we sought to use gene expression profiling to examine the host response to pNTM disease. Microarray analysis of whole-blood gene expression was performed on 25 subjects with pNTM disease and 27 uninfected control subjects with respiratory disease. Gene expression results were compared with phenotypic variables and survival data. Compared with uninfected control subjects, pNTM disease was associated with downregulation of 213 transcripts enriched for terms related to T cell signaling, including IFNG. Reduced IFNG expression was associated with more severe computed tomography changes and impaired lung function. Mortality was associated with the expression of transcripts related to the innate immune response and inflammation, whereas transcripts related to T and B cell function were associated with improved survival. These findings suggest that pNTM disease is associated with an aberrant immune response, which may reflect an underlying propensity to infection or result from NTM infection itself. There were important differences in the immune response associated with survival and mortality in pNTM disease.

Keywords: gene expression profiling; interferon-γ; nontuberculous mycobacteria.

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Figures

Figure 1.
Figure 1.
Boxplots of IFNG expression in pulmonary nontuberculous mycobacterial (pNTM) disease cases (gray) and control subjects (white). The central line, box boundaries, and whiskers represent the median, first and third quartiles, and the lowest and highest values lying within 1.5 times the interquartile range, respectively.
Figure 2.
Figure 2.
(A) Expression of IFNG and combined computed tomography (CT) score in pNTM cases. (B) Expression of IFNG and duration of pNTM disease.
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