This Week in TB R&D – 24 August 2010

A distinct whole-blood 86-gene transcriptional signature of active TB (Figure 2 in the paper)

Last week, a paper was published in Nature by Matthew Berry, Christine Graham et al. which received a fair amount of notice. The authors presented data identifying a probable TB gene signature in people infected with TB.

Initially the investigators examined genome-wide transcriptional profiles generated from RNA extracted from whole blood, purified neutrophils, monocytes, and T cells collected from healthy controls, patients with active TB (before treatment), and patients with latent TB. They observed a 393-transcript signature in patients with active TB and confirmed the presence of this 393-transcript signature in active TB patients in two distinct patient cohorts (London, an intermediate TB burden region and South Africa, a high-burden TB region). Furthermore, the observance of the signature was independent of ethnicity, age, or gender.

Interestingly, 10-25% of latent TB patients also carried the 393-transcript signature, which correlates with the recognized conversion percentage of latent TB to active TB in the general population. Drug treatment of patients with active TB resulted in a decrease in the 393-transcript after 2 months, and the apparent loss of the transcript after 12 months of treatment.

To rule out that the 393-transcript was a general inflammatory response, the investigators used further genetic mining tools to identify a 86-gene signature. Genes from this signature were further correlated with the interferon-γ and type-1 interferon-inducible gene pathway.

While interferon signaling pathways play critical roles, data presented in this paper may lead to not only a rapid-point of care diagnostic tool, but identification of novel biomarkers for disease progression and/or surrogate endpoint biomarkers essential for clinical drug development testing.

Is a point-of-care diagnostic tool close at hand based on the data from this paper? Should the type-1 interferon-inducible signature be more closely favored for development of a point-of-care diagnostic than the interferon-γ signature? Why or why not? Would a TB blood assay be more advantageous for tracking TB treatment prognosis? What are your thoughts and comments? Please share them below.

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