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Researchers Uncover Three New Biomarkers of Active Tuberculosis

NEW YORK (GenomeWeb) – A new metabolomic study has uncovered a handful of blood metabolites that appear to coincide with active, pulmonary disease in individuals infected with Mycobacterium tuberculosis

Researchers from Emory University, the National Center for Tuberculosis and Lung Disease, and the Atlanta Veterans Affairs Medical Center used high resolution metabolomic profiling to assess blood plasma samples from 17 individuals with active tuberculosis (TB) participating in a randomized control trial of a proposed vitamin D treatment for TB in the country of Georgia, as well as 16 control individuals sharing a home with the patients. 

Their findings, published online today in PLOS One, pointed to three blood metabolites — phosphatidylglycerol (PG), lysophosphatidylinositol (Lyso-PI), and acylphosphatidylinositol mannoside (Ac1PIM1) — that were consistently and significantly associated with active TB in the cases considered.

"Alone or together, these three metabolites demonstrated excellent classification accuracy for active TB cases, and therefore hold promise for further development as a metabolomics signature of active TB," co-first and corresponding author Jeffrey Collins, an infectious diseases researcher at Emory University School of Medicine, and his colleagues wrote.

The team noted that the "gold standard" test for confirming M. tuberculosis infection requires a time-consuming culturing method that is difficult to pull off without sufficient resources and infrastructure. Consequently, tests such as smear microscopy are typically used in resource-limited locales, despite questionable diagnostic performance and a reliance on sputum samples that can be difficult to obtain.

"There is an urgent need for point-of-care diagnostic tests for active TB, which can be performed on peripheral blood or urine samples," the authors explained. "The development of such tests will initially require identification of new putative biomarkers in the peripheral blood associated with active TB disease."

From their high-resolution mass spectrometry experiments and follow-up tandem mass spec, the researchers picked up 69 plasma metabolites that appeared to distinguish between 17 active TB cases (including three cases of multidrug-resistant TB) and 16 controls individuals from the same households, who were not tested for TB.

The team noted that all 17 individuals with active TB had at least one of three most significantly associated metabolites in their blood plasma, while 14 had two or more. In contrast, just eight of the household contact control individuals had at least one of these metabolites in their blood plasma, and two of the metabolites were found in one household control individual.

After narrowing in on these metabolites, the researchers not only followed up by tandem mass spec analyses, but also assessed the classification accuracy of the potential metabolite markers alone or in combination.

"Our pilot data suggests that plasma [high-resolution metabolomics] may hold significant promise for characterization of [M. tuberculosis]-associated metabolites in patients with active TB disease," the authors concluded. "If confirmed in larger studies that include diverse patient populations and relevant controls, further development of the most discriminatory metabolites may inform development of diagnostic biomarkers for active TB."

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