Abstract
Background: Increasing expression of programmed death-1 (PD-1) in patients with nontuberculous mycobacteria lung disease (NTM-LD) has been reported, but its role in clinical characteristics and outcomes remains unclear. Methods: We enrolled 96 participants, including 46 with Mycobacterium avium complex (MAC)-LD, 23 with M. abscessus (MAB)-LD, and 27 controls. We measured expressions of PD-1, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and regulatory T (Treg) cells on CD4+ lymphocytes and myeloid-derived suppressor cells (MDSCs) and analyzed their association with clinical features and radiographic outcomes. Results: The percentage of PD-1 on CD4+(PD-1+CD4+) lymphocytes and MDSCs were higher in the MAC-LD group than the controls. There were no intergroup differences regarding CTLA-4+CD4+ lymphocytes. Higher PD-1+CD4+ lymphocytes were found in M. intracellulare- and M. avium-LD than in other MAC-LD. Positive sputum acid-fast stains and fibrocavitary radiographic lesions were correlated with elevated PD-1+CD4+ lymphocytes and Treg cells. The percentage of PD-1+CD4+ lymphocytes at the initial and 2 months of follow-up significantly predicted subsequent radiographic progression. Conclusion: As markers of immune tolerance, PD-1+CD4+ lymphocytes and MDSCs were higher in MAC-LD patients. The levels of PD-1+CD4+ and Treg cells were correlated with high mycobacteria bacilli burden in NTM-LD. Monitoring the expressions of PD-1+CD4+ lymphocytes may predict radiographic progression.
Highlights
Nontuberculous mycobacteria lung disease (NTM-LD) has become an important clinical concern [1,2] because the prevalence of NTM infection has increased over the last two decades, the etiology remains unclear [3,4]
There were no significant differences in the radiographic FC pattern and nodular bronchiectasis (NB) pattern between the Mycobacterium avium complex (MAC)-LD and M. abscessus (MAB)-LD groups
The programmed death-1 (PD-1)+CD4+ lymphocytes in the patients with MAC-LD and the myeloid-derived suppressor cells (MDSCs) in those with MAC-LD and MAB-LD were significantly higher compared to the controls
Summary
Nontuberculous mycobacteria lung disease (NTM-LD) has become an important clinical concern [1,2] because the prevalence of NTM infection has increased over the last two decades, the etiology remains unclear [3,4]. Only around one-third of patients with positive sputum cultures for MAC and MAB clinically have the disease [6,7], which highlights the importance of individual vulnerability to NTM infection [8]. The immune status of NTM-infected patients can become compromised through complex host-pathogen interactions, and recent studies have reported that the immune status of peripheral blood mononuclear cells (PBMC) is suppressed by MAC [9,10]. Previous studies have shown that the expression of programmed death-1 (PD-1), a negative co-receptor for T cell activation [11] is higher in patients with MAC-LD, and may play a role in decreasing host immunity [10]. Increasing expression of programmed death-1 (PD-1) in patients with nontuberculous mycobacteria lung disease (NTM-LD) has been reported, but its role in clinical characteristics and outcomes remains unclear. Monitoring the expressions of PD-1+CD4+ lymphocytes may predict radiographic progression
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