Editors' ChoiceInfectious Disease

A Lesson for TB from Antiviral Immunity

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Science Translational Medicine  16 Mar 2011:
Vol. 3, Issue 74, pp. 74ec37
DOI: 10.1126/scitranslmed.3002364

The control and prevention of tuberculosis (TB) infections in the United States has been very successful, leading to a substantial drop in the prevalence of the disease. This has been achieved through the widespread adoption of screening programs that detect individuals exposed to the bacterium that causes TB, Mycobacterium tuberculosis. One issue that arises during screening for TB, however, is that the assays cannot distinguish persons who have an active infection from those with latent disease. This distinction is important because patients with active disease need to be isolated from close contacts and treated with a combination of powerful antibiotics, some of which have unpleasant side effects. One way physicians manage this dilemma is to collect sputum samples from patients to see whether the TB organism can be detected in cultured specimens. The problem is that this process can take several weeks to complete, during which time patients may be given medications for active TB infection when in fact they have a latent, quiescent form of the disease.

Now, Harari et al. report the development of a new diagnostic test that may allow physicians to quickly decipher which patients have active TB and which have the latent form of the disease. The authors borrowed an observation from studies of antiviral immunity showing that activated virus-specific T cells produce a characteristic cytokine profile. The authors hypothesized that the cytokine profile for T cells from individuals suspected of having TB infection could be used to differentiate between the active and latent forms of the disease. Using a flow cytometry assay in a cohort of 283 patients known to have TB, they found that CD4+ T cells that were specific for Mycobacterium tuberculosis antigens in individuals diagnosed with latent infection secreted the cytokines interferon-γ, interleukin-2, and tumor necrosis factor–α (TNF-α); in contrast, pathogen-specific T cells from those diagnosed with active disease only produced TNF-α. The investigators validated their results in a second independent cohort of 101 patients whose TB status they did not know and were able to establish a highly sensitive and specific cut-off value for their assay. This exciting finding will probably have to be validated in larger studies, and the assay may not currently be practical in resource-limited areas of the world where TB is far more prevalent. But the findings represent an important advance that may soon allow clinicians to quickly triage TB patients to the correct treatment regimen, thus limiting the morbidity and cost that arises from the delays built into the current diagnostic protocol.

A. Harari et al., Dominant TNF-α(+) Mycobacterium tuberculosis–specific CD4(+) T cell responses discriminate between latent infection and active disease. Nat. Med. 17, 372–376 (2011). [PubMed]

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