Abstract
Mycobacterium abscessus complex (MABC) infection has a devastating impact on the course of cystic fibrosis (CF) and non-CF lung disease. Diagnosis of MABC pulmonary disease is challenging, and current diagnostic approaches lack accuracy, especially in CF. In this study, we aimed to establish an MABC-specific interferon-γ release assay to detect host immune responses to MABC and improve diagnostics of MABC infection by the detection of antigen-specific T cells. Four species-specific proteins of MABC were overexpressed in an Escherichia coli expression system. Purified proteins were used to stimulate peripheral blood mononuclear cells of study subjects in an ELISpot assay. Interferon-γ response of 12 subjects with established diagnosis of MABC infection (10 CF and two non-CF) was compared with 35 controls (22 CF and 13 non-CF) distributed to three control groups, 17 CF subjects without NTM infection, nine subjects with NTM infection other than MABC, and nine subjects with tuberculosis. Cellular in vitro responses in the MABC group were stronger than in the control groups, especially toward the protein MAB_0405c (39 vs. 4 spots per 300,000 PBMC, p = 0.004; data represent mean values) in all patients and also in the subgroup of CF subjects (39 spots vs. 1 spot, p = 0.003). Receiver operating characteristic curve analysis indicated that spot numbers of at least 20 were highly predictive of MABC infection (all patients: area under curve 0.773, sensitivity 58%, and specificity 94%; CF patients: area under curve 0.818, sensitivity 60%, and specificity 100%). In conclusion, we identified MAB_0405c as a protein that may stimulate MABC-specific interferon-γ secretion and may add to the diagnosis of MABC infection in affected patients.
Highlights
Members of the Mycobacterium abscessus complex (MABC) are rapidly growing mycobacteria causing lung infection predominantly in patients with preexisting lung diseases with often devastating impact (Park and Olivier, 2015)
The abundance of more rapidly growing bacteria colonizing the respiratory tract of cystic fibrosis (CF) patients, e.g., Pseudomonas aeruginosa, frequently leads to overgrowth of mycobacterial cultures (Griffith et al, 2007)
In our own previous studies, we investigated a comparative T-cell-based immunologic approach for the detection and immune characterization of MABC infection in CF patients (Steindor et al, 2015)
Summary
Members of the Mycobacterium abscessus complex (MABC) are rapidly growing mycobacteria causing lung infection predominantly in patients with preexisting lung diseases with often devastating impact (Park and Olivier, 2015). MABC is the most frequently isolated species of non-tuberculous mycobacteria (NTM) in Caucasian CF populations (Hill et al, 2012) and the second largest group of NTM in non-CF lung disease patients, after the Mycobacterium avium complex (Prevots et al, 2010). MABC causes the most rapid decline of lung function in CF patients, often resulting in early end-stage lung disease (Qvist et al, 2016). The diagnosis of MAPD is based on clinical, radiological, and microbiological criteria provided by the American Thoracic Society (Griffith et al, 2007). The abundance of more rapidly growing bacteria colonizing the respiratory tract of CF patients, e.g., Pseudomonas aeruginosa, frequently leads to overgrowth of mycobacterial cultures (Griffith et al, 2007)
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