Biomarkers & TB

T-cell Biology Reveals Better Tools for Tuberculosis Detection

Tuberculosis (TB) is a worldwide epidemic, accounting for 1.4 million deaths in 2019. It is the deadliest infectious disease, surpassing even HIV/AIDS. But this level of mortality, represents progress. Groups like the World Health Organization (WHO) and the Gates Foundation have made significant investments in attempting to better treat and prevent the spread of tuberculosis. Yet the sheer number of deaths makes it clear that there is still a staggering amount of work to be done, and opportunities to better understand and treat this disease, especially in light of the current pandemic. Evidence suggests that COVID-19 might result in the development of 1.4 million more TB cases than otherwise expected in the next 5 years.

Jyothi Rengarajan, PhD, Associate Professor of Infectious Diseases, has made breakthroughs in understanding the complex interactions between TB and the immune system, our body’s network of cells dedicated specifically to fighting disease. In her work, she has found and patented biomarkers that effectively distinguish between active, latent, and pulmonary versus non-pulmonary forms of disease.

Jyothi Rengarajan, PhD
Jyothi Rengarajan photo

While many tests can detect TB, the most common technique of sputum testing can take weeks to return a result, and very few can accurately or consistently distinguish TB. Rengarajan’s toolkit can test for TB much more quickly than sputum tests, and has the ability to accurately distinguish active versus latent TB.  Better testing means better and quicker clinical decision making that can save lives. That’s especially true with Rengarajan’s test, which also provides more information about the amount of bacteria present in a patient, a facet that might potentially allow physicians to track the course of the disease.

Rengarajan used her deep experience in immunology to develop this test. Her group explores how the bacteria that causes TB, M. tuberculosis, manipulates our immune system at the molecular level. Our bodies, through countless generations of living in environments with pathogens, have gotten very good at responding to disease. Part of this disease-fighting ability is hard-coded into some of our cells. But the other part, our adaptive immune system, is able to respond to diseases our body has never seen before.

TB stock graphic

For TB, our adaptive immune systems play a primary role in the response to the disease. Nevertheless, TB displays a distinct ability to evade destruction. Even after an immune system response, TB can hide in cellular compartments, going from an “active” to “latent”, or non-active, state. Latent TB can come back with a vengeance in patients with weakened immune systems, like is characteristic of AIDS: one in four deaths of people with HIV worldwide are due to TB. Sputum tests can’t detect latent TB, and other tests in wide use have concerning deficiencies in accuracy.

Rengarajan was able to find biomarkers associated with these active and latent states: in other words, she and her team were able to find out the specific level of certain cell populations that were associated with active or latent states of TB. When TB infection is active, different types of T cells predominate than when latent infection is occurring. Rengarajan’s group capitalized on this insight of immunology to develop this platform. They’ve published their work extensively in the academic literature, confirming the specificity and sensitivity of these tests in blind studies with TB patients.

Rengarajan’s work has the potential to significantly improve the treatment of TB, especially in developing countries where current tests can take precious time. This creates an opportunity for the development of assays that capitalize on Rengarajan’s well-developed biomarker science. “Dr. Rengarajan’s research sheds new light on the pressing issue of TB diagnosis and is a fantastic example of high-quality academic research ready for a commercial partner to bring it to market,” notes licensing associate John Nicosia. While this platform has been developed for use with a flow cytometer, the creation of kits for similar tests such as interferon-gamma release assays (IGRAs) like QuantiFERON serve as a promising proof-of concept that modular testing systems can be developed. As investment from groups like WHO and the Gates Foundation continues to be directed toward better diagnostics for TB, her research may well become a clinical reality.

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