Pulmonary non-tuberculous mycobacterial infection in patients without predisposing condition, morphological and immunological overview of a french cohort

Abstract

Introduction: Nontuberculous mycobacteria may cause lung disease (pNTM). pNTM may present as a pattern of bronchiolar nodules and bronchiectasis (NB), which concerns a majority of postmenopausal women without underlying lung disease. These patients present a remarkably phenotypic homogeneity associating above average height, thinness, high frequency of mitral valve prolapse and thoracic wall abnormalities, suggesting a multi-system genetic disease.

Methods: Retrospective analysis of patients with pNTM without risk factors (2000-2016). Age and sex-matched controls (2/1).

Results: 50 patients included (median age 65 years, women 90%); NB 44, cavitary 6. Microbiology: M. avium complex 42, M. kansasii 6, M. abscessus complex 5, M. xenopi 3, others 2.

Morphological characteristics: table

Immunoglobulin assay: decrease in at least one subtype in 27%. Lymphocyte phenotyping (N=38): CD19<80 /mm3=5. 47% have a decreased level of memory B cells. IFNγ and IL12 production and response pathways (N=31): Decreased IFNγ production in response to BCG (p<0.0001) and BCG+IL12 (p=0.0002). Decreased IL12p40 production in response to BCG+IFNγ (p=0.045). Exome (N=24): No abnormality in IL12RB1, IFNGR1, IFNGR2, IL12B, IRF8, ISG15, NEMO, STAT1 and CYBB

Conclusion: Our patients present the morphotype classically associated with NB pNTM. They have a decreased production of IFN-gamma in whole blood after stimulation. A significant proportion has a decrease in antibody production and a decreased level of memory B cells. This may reflect a larger immunodeficiency than previously suspected. Exome analysis is underway.