Blood protein signature points to faster TB diagnosis

Tuberculosis remains a global health threat, and faster, easier diagnosis is essential to control transmission and reach the World Health Organizations goals of ending TB. Current diagnostic approaches often rely on sputum samples, which can be hard to obtain or insensitive in many patients. In earlier work, Zaynab Mousavian and her team identified a 12-marker plasma protein signature linked to TB disease severity. Building on that discovery, the new study set out to test how well that signature works in different populations and whether it could be simplified without losing accuracy. The researchers tested the signature in independent cohorts from Sweden and Italy, including people with TB infection and those with other respiratory diseases. In total they analyzed 317 samples from 273 donors, giving a diverse set of blood specimens to assess whether a blood-based, non-sputum approach could reliably distinguish active TB disease from infection and other lung conditions. The study aimed to produce a smaller, more practical set of protein markers that could be used in future clinical tests.

To make the test more practical, the team condensed the original 12 proteins into smaller panels of six and four markers and then evaluated their performance across the cohorts. The six-protein signature included CDCP1, VEGFA, IFN- γ , CXCL9, IL6 and MCP-3, while the four-protein version used CDCP1, VEGFA, IFN- γ and CXCL9. Both reduced signatures remained highly enriched for TB disease and in some comparisons even improved accuracy when tested against ten other published protein signatures for TB disease. The study reports sensitivity for distinguishing TB disease from TB infection at 89% across the entire combined cohort and 97% in the Italian cohort, with specificity fixed at 70%. These results show that a small set of plasma proteins can robustly separate active TB from infection and other respiratory conditions in these independent Swedish and Italian samples, supporting the potential of these markers for a non-sputum-based diagnostic approach.

If these condensed protein signatures hold up in larger and more varied populations, they could change how clinicians screen for and diagnose TB. A blood-based test built on CDCP1, VEGFA, IFN- γ , CXCL9, IL6 and MCP-3 (or the even smaller four-protein set) would be easier to use in settings where sputum collection is difficult or slow, and could speed identification of people with active disease so they receive treatment sooner. Faster, simpler diagnosis would help cut transmission and support efforts to meet the World Health Organizations goals of ending TB. The authors note that these signatures merit further evaluation as clinically relevant markers, meaning additional studies are needed to validate performance across other countries, patient groups and real-world testing platforms before they could become routine tools in TB control.