CHIN-CHUNG SHUWu L.S.-H.Wu M.-F.HSIN-CHIH LAIWang P.-H.Cheng S.-L.JANN-YUAN WANGCHONG-JEN YU2020-07-032020-07-0320191043-4666https://scholars.lib.ntu.edu.tw/handle/123456789/508168Summary at a Glance: The diagnosis and progression of nontuberculous mycobacteria lung disease (NTN-LD)are important for clinical judgement but cannot easily be predicted. The immunological response of mono- and poly-functional T cells, a representative of host reactivity to NTM, could be a surrogate biomarker for disease and progression prediction. Background: Mycobacterium avium complex (MAC)and M. abscessus (MAB)induced lung disease (LD)have become a clinical concern. Predicting clinical disease relevance and progression is important, but suitable biomarkers are lacking. The host immune response of mono- and poly-functional T cells might aid in clinical judgement. Methods: We enrolled 140 participants, including 42 MAC-LD, 25 MAB-LD, 31 MAC airway colonization (MAC-Co), 15 MAB-Co patients, and 27 healthy controls. Their blood mono- and poly-functional T cells were measured and analyzed after in-vitro stimulation. Results: Patients with MAC-LD generally had lower total IFN-γ+, total TNF-α+ and triple-positive T cells but higher mono-IL-2+ expression than the controls and MAC-Co group. The MAB-LD group had lower total IL-2 and triple positive cells than the controls and colonization group. Multivariate analysis revealed that body mass index (BMI), mono-IL2+ CD4+ and triple positive-CD8+ cells (PMA stimulation)significantly predicted MAC-LD from the controls. By contrast, male gender and triple positive-CD4+ cells predicted MAC-LD from colonization. On the other hand, the triple positive-CD4+ cells (PMA stimulation)alone or together with the mock/MAB ratio of IL-2+/TNF-α+ CD4 cells could predict MAB-LD in the MAB-Co group or the controls. Among MAC/MAB-LD patients without anti-mycobacterial treatment, MAC-specific mono-IFN-γ+ CD4+ cells and PMA-induced triple positive-CD4+ cells were correlated with progression, with an area under the ROC curve of 0.875. Conclusions: The patients with MAC/MAB-LD had attenuated poly-functional T cells. The triple-positive CD4+ cells could be useful in diagnosing disease from colonization. MAC-specific mono-IFN-γ+ CD4+ cells and triple positive-CD4+ might predict radiographic progression, which could be useful in making treatment decisions. ? 2019 Elsevier Ltd[SDGs]SDG3gamma interferon; tumor necrosis factor; cytokine; adult; Article; atypical mycobacteriosis; atypical Mycobacterium; bacterial colonization; blood level; body mass; CD4+ T lymphocyte; CD8+ T lymphocyte; controlled study; decision making; disease course; female; human; immune response; immunocompromised patient; lung disease; major clinical study; male; middle aged; Mycobacterium abscessus; nonhuman; prediction; priority journal; prospective study; risk assessment; T lymphocyte; Taiwan; aged; blood; case control study; diagnostic imaging; disease exacerbation; immunology; lung disease; pathology; receiver operating characteristic; risk factor; T lymphocyte; Aged; Case-Control Studies; Cytokines; Disease Progression; Female; Humans; Lung Diseases; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Risk Factors; ROC Curve; T-Lymphocytesjournal article10.1016/j.cyto.2019.05.001310854552-s2.0-85065400831