Gene expression in pulmonary non-tuberculous mycobacterial infection

The factors predisposing towards the development of pulmonary non-tuberculous mycobacterial disease (pNTM) and influencing disease progression remain unclear. Impaired immune responses have been reported in individuals with pNTM but data are limited and inconsistent. This study aimed to use gene expression profiling to examine the host response to pNTM. Microarray analysis of whole blood gene expression was performed on 25 subjects with pNTM and 27 uninfected controls with respiratory disease. Gene expression results were compared to phenotypic variables and survival data. Compared with uninfected controls, pNTM was associated with down-regulation of 213 transcripts enriched for terms related to T cell signalling including IFNG. Reduced IFNG expression was associated with more severe CT 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 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. Gene expression was performed on a total 89 samples taken from 69 subjects recruited as part of a larger study. The current analysis was performed on a subset of 52 subjects (25 pNTM cases and 27 controls) indicated in the metadata. However as background correction, normalisation and summarisation was performed using all 89 samples, data on the additional samples is provided to allow for reproducibility. FEV1 = forced expiratory volume in 1 second, percent predicted; FVC = forced vital capacity, percent predicted; TLC = total lung capacity, percent predicted; TLCO = transfer factor for carbon monoxide, percent predicted; KCO = transfer factor for carbon monoxide, corrected for alveolar volume, percent predicted; CTscore = composite NTM CT score; CT_extent = CT score for bronchiectasis extent; CT_severity = CT score for bronchiectasis severity; CT_TIB = CT score for tree-in-bud opacification; CT_nodules = CT score for nodules; CT_nod_cav = CT score for cavitating nodules; CT_severe_cav = CT score for severe cavitation; CT_aspergilloma = CT score for aspergilloma; CT_consolidation = CT score for consolidation; Albumin = serum albumin g/L; CRP = serum c-reactive protein mg/L; Neutrophils = blood neutrophil count, cells x 10E9/L; Disease_duration = duration from diagnosis to recruitment, years; Death = death during study (1 = yes, 0 = no); Survival_time = survival from study enrolment, weeks.