S145 THE IDENTIFICATION OF DISTINCT GENE EXPRESSION PROFILES IN LATENT AND ACTIVE TUBERCULOSIS

¹MPR Berry, ²D Chaussabel, ³OM Kon, ²J Banchereau, ¹A O’Garra. ¹Division of Immunoregulation, National Institute for Medical Research, London, UK, ²Baylor Institute for Immunology Research and Baylor Research Institute, Dallas, USA, ³St Mary’s Hospital, Imperial College Healthcare NHS Trust, London, UK

Introduction: Tuberculosis is a major and increasing cause of morbidity and mortality worldwide caused by infection with Mycobacterium tuberculosis (MTb). However, the majority of individuals infected with MTb remain asymptomatic, apparently retaining the infection in a quiescent form. It is thought that this latent infection is maintained by an active immune response. The immune response to MTb is complex and remains incompletely characterised. We hypothesised that obtaining whole genome expression profiles from the blood of patients with either latent or active tuberculosis could lead to improved insights into the protective immune response, as well as the development of potential biomarkers.

Methods: We recruited patients with active pulmonary tuberculosis and latent tuberculosis. All active tuberculosis patients included in the analysis were culture positive and all latent patients included were positive by both tuberculin skin test and interferon-gamma release assay (IGRA). Potentially immunosupressed individuals were excluded. We also recruited healthy controls, who tested negative by both skin test and IGRA. Whole blood was collected from all participants before treatment. RNA was extracted from the whole blood and microarray analysis performed using Illumina Sentrix Human-6 V2 BeadChip arrays (>48 000 probes). Statistical analysis and hierarchical clustering of samples was performed using Genespring, v7.1.3.

Results: After filtering out undetected transcripts and those with less than twofold change, 6269 transcripts were used for unsupervised clustering analyses by Pearson correlation. This revealed distinct expression profiles, or “disease signatures”, corresponding to the clinical diagnosis of latent or active tuberculosis. These disease signatures held true across the broad number …