Host transcriptional response to TB preventive therapy differentiates two sub-groups of IGRA-positive individuals

<jats:title>Abstract</jats:title><jats:p>We investigated the longitudinal whole blood transcriptional profile responses to tuberculosis preventive therapy of 18 IGRA-positive tuberculosis contacts and IGRA-negative, tuberculosis-unexposed healthy controls.</jats:p><jats:p>Longitudinal unsupervised clustering analysis with a subset of 474 most variable genes in antigen-stimulated blood separated the IGRA+ participants into two distinct subgroups, one of which clustered with the IGRA-negative controls. 117 probes were significantly differentially expressed over time between the two cluster groups, many of them associated with immunological pathways important in mycobacterial control.</jats:p><jats:p>We contend that the differential host RNA response reflects lack of <jats:italic>M.tuberculosis</jats:italic> (<jats:italic>Mtb</jats:italic>) viability in the group that clustered with the IGRA-unexposed healthy controls, and <jats:italic>Mtb</jats:italic> viability in the group (1/3 of IGRA-positives) that clustered away.</jats:p><jats:p>Gene expression patterns in the blood of IGRA+ individuals emerging during the course of PT, which reflect <jats:italic>Mtb</jats:italic> viability, could have major implications in the identification of risk of progression, treatment stratification and biomarker development.</jats:p>