Blood test signature separates TB from other lung infections

Diagnosing pulmonary tuberculosis (PTB) can be difficult when symptoms overlap with other respiratory infections, and researchers are searching for reliable tests that do not rely on sputum. In a study led by Zaynab Mousavian, investigators turned to plasma multiomics — the combined measurement of proteins and small molecules in blood — to look for patterns that set PTB apart. The study compared people with PTB identified by sputum culture and 204 were controls in whom PTB was excluded. By studying blood samples rather than respiratory specimens, the team aimed to find markers that could be used in situations where sputum is hard to collect or provides unclear results. Zaynab Mousavian and colleagues focused on signatures that could serve both as a rapid triage tool to flag people who need further testing and as a potential non-sputum diagnostic test that confirms disease. The approach centers on searching for a small set of markers in plasma that, when considered together, could reliably tell clinicians whether an infection is likely PTB rather than another respiratory illness.

Using plasma multiomics data from their study groups, the team identified a compact five-marker signature composed of IFN.gamma, IL.22, IL.10, methionine and oxoproline. This combination was tested in a separate test set, where it achieved an area under the receiver-operating characteristic curve (AUC) of 0.97 (95% CI: 0.95-1.00), indicating very strong discrimination between PTB and other respiratory infections. The signature showed 98% and 84% sensitivity at 70% and 98% specificity respectively, performance levels the authors note meet WHO target product profiles for both non-sputum triage and diagnostic TB tests. Those performance metrics mean the panel correctly identified most true PTB cases while also maintaining specificity at thresholds relevant for different clinical uses. By combining two cytokines associated with immune response (IFN.gamma and IL.22), an anti-inflammatory cytokine (IL.10) and two small molecules (methionine and oxoproline), the signature draws on diverse biological signals captured by plasma multiomics.

The finding that a five-marker blood signature can distinguish PTB from other respiratory infections has potentially important implications. Because the signature meets WHO target product profiles for both triage and diagnostic uses, it could form the basis for new non-sputum tests that help clinicians screen and diagnose TB more quickly, especially in settings where sputum is unavailable or unreliable. A blood-based test built on IFN.gamma, IL.22, IL.10, methionine and oxoproline could streamline patient pathways by flagging people who need further confirmatory testing and, in some contexts, supporting diagnosis without sputum. However, moving from a promising signature to a widely used clinical test will require further development, standardization and validation in varied populations and settings to confirm real-world performance. Still, the study led by Zaynab Mousavian demonstrates that plasma multiomics can reveal compact, high-performing marker sets that meet international targets and warrant further translation into accessible tests.