Clinical and immunological characteristics of patients with pulmonary Mycobacterium abscessus disease without cystic fibrosis

<b>Background:</b><i>Mycobacterium abscessus</i> is a non-tuberculous mycobacterium notorious for causing difficult to treat pulmonary infections in susceptible individuals, mainly patients with cystic fibrosis (CF). However, we noticed increasing numbers of non-CF patients. <b>Aims:</b> To characterize the clinical characteristics of a cohort of non-CF patients with <i>M. abscessus</i> disease and investigate whether immune defects explain an increased vulnerability. <b>Methods:</b> We included and retrospectively studied 18 non-CF patients from our NTM expert centre who met the ATS criteria for pulmonary <i>M. abscessus disease</i>. Prospectively, we performed stimulations of peripheral blood mononuclear cells and whole blood from 15 patients and 15 healthy controls to investigate their cytokine production after 24 hours and 7 days. <b>Results:</b> Patients were predominantly women (61%) with a mean age of 58 years (range 36-75 years). Many had pre-existent pulmonary diseases, such as bronchiectasis (47%), COPD (39%) and asthma (29%). Twenty-four hours after stimulation with LPS/IFN-γ, levels of TNFα and IL-6 were lower in patients than controls. Patients also produced significantly less IL-1β compared to controls in response to <i>M. abscessus</i>, while IL-1Ra production was higher. After 7 days, lower IFN-γ and IL-17 levels were measured in patients in response to <i>C. albicans</i>. IL-12/IL-18-induced IFN-γ was also lower in patients compared to controls. <b>Conclusion:</b> Most, but not all patients with <i>M. abscessus</i> disease had an underlying chronic structural lung disease. Also, they showed imbalances in both the innate and adaptive immune response, which impair their host defence and might worsen clinical outcome.