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Assay detects latent tuberculosis

Biomarker signatures could help doctors assess a patient’s risk of dormant bacteria waking up again

by Celia Henry Arnaud
February 13, 2019 | APPEARED IN VOLUME 97, ISSUE 7


Credit: Adapted from Integr. Biol.
Mononuclear blood cells exposed to a variety of TB-specific and non-TB specific antigens (left) secrete proteins that can be detected by antibodies (colorfoul Y's) on an array of microring resonators (right).

Nearly a quarter of the world’s population has latent tuberculosis infection (LTBI). These people don’t have symptoms of the infection because the TB bacteria living inside them are dormant. In about 10% of those people, the bacteria will wake up, but diagnosing latent TB and predicting who is at risk for reactivating is hard.

A team led by Ryan C. Bailey of the University of Michigan and Patricio Escalante of Mayo Clinic reports an assay that reveals diagnostic signatures that doctors could use to both diagnose latent TB and evaluate a patient’s reactivation risk (Integr. Biol. 2019, DOI: 10.1093/intbio/zyz001).

The assay provides information about how immune cells in a patient respond to threats. Some of these responses may indiciate increased risk of reactivation.

To get information about these responses, the researchers use arrays of microring resonators to detect proteins secreted by mononuclear blood cells—a type of immune cell—in response to antigens related or unrelated to TB. When antibodies on the resonator surface bind a secreted protein, the refractive index of the device changes, producing a shift in the device’s optical readouts. The researchers exposed immune cells from 50 people with LTBI to five substances: TB-specific peptides, the protein derivative used in the tuberculin skin test, the yeast Candida albicans, and positive and negative controls.

“By testing cells' secretion patterns that have nothing to do with TB, we’re actually monitoring basal immune function,” Bailey says. By subtracting the responses to the non-TB substances from the TB ones, they revealed signatures specific to different states of LTBI. “We saw almost three times as many biomarkers that correlated with different TB states,” Bailey says.

“LTBI is a really hard problem,” says Brian M. Paegel, a scientist at Scripps Research’s Florida campus who works on diagnostic technology development. The researchers behind the new study “are taking it to a new level. They’re looking at a cellular response to the presence of those antigens, providing a potentially richer data set to tease out the presence of LTBI.”

But first the researchers need to study more TB patients. “To further validate this biomarker signature we are working with a TB clinic in Tijuana, where TB prevalence and reactivation rates are much higher than the US,” Bailey says.



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