February 22, 2016
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Gene expression method detects active TB

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Researchers have identified three genes whose expression may indicate active pulmonary tuberculosis, thereby allowing health care workers to diagnose patients without the use of sputum samples, according to recent data.

“Despite advances in diagnosis and treatment [of TB], there is still a large burden of disease, and accurate diagnosis of tuberculosis remains difficult,” the researchers wrote. “Traditional methods such as tuberculin skin testing and interferon gamma release assays are unable to distinguish between latent tuberculosis and active tuberculosis, and have reduced sensitivity in HIV-positive patients. The more recently developed Xpert MTB/RIF assay [Cepheid] has greatly improved diagnostic power, but is associated with reduced accuracy in HIV-positive patients and is not useful for monitoring treatment response.”

In 2014, WHO called for researchers to develop new TB diagnostics that do not require sputum and are capable of high sensitivity in children as well as patients with HIV. To achieve this goal, Stanford researchers examined 14 datasets (n = 2,572) collected from two public gene expression microarray repositories for genomic biomarkers of TB. Samples were obtained from patients with active TB, latent TB, a history of TB vaccination or other unrelated diseases. Comparing the gene expression of these samples within the three largest datasets (n = 1,023) revealed three affected genes, which the researchers theorized could be used to diagnosis active TB from a patient’s whole blood sample.

“The three-gene set could improve clinical diagnosis and treatment response monitoring, although this needs to be confirmed by prospective validation with a targeted assay,” the researchers wrote. “The parsimony of the three-gene set should ease translation to clinical practice and might prove cost-effective in the resource-poor environments in which tuberculosis is present.”

The researchers validated their prospective method by testing its ability to determine active TB within different subgroups of the accessed datasets. The three-gene set accurately determined active TB cases from those with no illness (mean sensitivity = 0.93; mean specificity = 0.97), latent TB (mean sensitivity = 0.88; mean specificity = 0.85) and other examined diseases (mean sensitivity = 0.82; mean specificity = 0.79). Results were accurate when used among adults and children from multiple countries, and were not confounded by HIV, bacterial drug resistance or bacillus Calmette-Guérin vaccination.

“Multiple diagnostic host gene signatures for tuberculosis have been published,” the researchers wrote. “We show here that our signature is either smaller, or has better characteristics, or both, when compared to prior diagnostics. The increasing interest in using host gene expression signatures to diagnose tuberculosis suggests that these methods may become a part of the clinical toolkit in the near future.– by Dave Muoio

 

Disclosure: Sweeney reports previous work as a scientific adviser with Multerra Biosciences and a pending patent related to TB diagnosis. All other researchers report no relevant financial disclosures.