Immunological Markers of Lung Disease Due to Non-Tuberculous Mycobacteria

Andrew Lim,Dino Bee Aik Tan,Grant Waterer,Patricia Price,Caris Allison,Ben Oliver

doi:10.1155/2010/347142

Abstract

Lung disease due to nontuberculous mycobacteria (NTM) is a poorly understood condition that is difficult to treat. Treatment remains problematic as few tools are available to help clinicians monitor disease progression or predict treatment outcome. In this study, plasma levels of several inflammatory molecules and the frequency of circulating T cell subsets were measured in patients with NTM lung disease and known treatment status, and compared with their adult offspring and with unrelated healthy controls. Plasma levels of the chemokine CXCL10 and IL18 were assessed for associations with treatment efficacy. CXCL10 was higher in patients than adult offspring (p < 0.001) and unrelated controls (p< 0.001). Plasma CXCL10 was also lower in patients who responded well to therapy or who controlled their infection without requiring therapy, when compared to patients who did not respond to therapy (p= 0.03). Frequencies of activated (HLADR+) CD4+T cells were higher in patients than adult offspring (p< 0.001) and unrelated controls (p< 0.05), with the highest frequencies in individuals who had completed at least 6 months of treatment. Frequencies of activated (CD38+) CD8+T cells in most treatment responders were similar to unrelated controls. Low plasma levels of CXCL10 may reflect successful control of NTM lung disease with or without therapy. Compared with responders, patients who responded poorly to treatment generally had higher plasma levels of CXCL10 and IL18, and higher frequencies of activated CD8+T cells.

Highlights

Non-tuberculous mycobacteria (NTM) comprise species of mycobacteria other than the Mycobacterium tuberculosis (MTb) complex and M. leprae
Patients with NTM lung disease (NTMLD) display elevated plasma CXCL10 and IL-18 and successful control of disease is associated with lower levels of both molecules
Plasma levels of CXCL10 were lower in responders than non-responders, but remained elevated compared with offspring (p = 0.004) or unrelated controls (p = 0.002) (Fig. 1a)

Summary

Introduction

Non-tuberculous mycobacteria (NTM) comprise species of mycobacteria other than the Mycobacterium tuberculosis (MTb) complex and M. leprae. They are ubiquitous environmental organisms that rarely cause disease in immunocompetent hosts. NTM often cause extrapulmonary or disseminated disease in immunocompromised individuals (including HIV-infected patients), but pulmonary infections are uncommon. The susceptibility of a subset of otherwise healthy adults to NTM lung disease (NTMLD) and the pathogenesis of this condition remain poorly understood. Treatment of NTMLD and monitoring of treatment responses remains problematic. Other problems include poor adherence to treatment regimens (minimum 3 drugs for at least 18 months), side effects and adverse interactions with other medications. There are few tools to accurately predict treatment response or relapse, or to monitor disease progression

Methods

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Conclusion