Nasal gene signals detect TB in people with HIV in Uganda

Pulmonary tuberculosis (TB) remains hard to diagnose in people living with HIV, and delays can cost lives. Researchers led by corresponding author Nisreen Khambati set out to explore a new, less invasive way to find signs of TB by looking not for the bacteria but for how the person’s own cells respond. Their idea began with a simple fact: the first contact between TB bacteria and the human body happens in the upper airway. That led the team to collect cells from the nose of adults in Uganda who were ART-Naive, newly diagnosed with HIV and had symptoms of pulmonary TB, and to compare them with nasal samples from people with HIV who did not have TB. The work is described as a proof-of-concept study: it is an early demonstration that patterns of gene activity in the nose might carry diagnostic information. By focusing on the host response in a minimally invasive sample, the investigators aimed to find biomarkers that could be easier to collect than sputum or blood and that might work in groups where TB diagnosis is especially difficult.

To search for diagnostic signals the team collected nasal cells and blood and used RNA sequencing to read which genes were switched on or off. They then looked for differentially expressed genes and enriched pathways that distinguished people with HIV and TB disease from those with HIV without TB. The researchers also applied supervised machine-learning to the gene expression data to build models that could predict TB status. In their analysis they compared nasal gene profiles to blood gene profiles from the same participants. The study found distinct nasal gene expression patterns associated with TB that were not seen in blood. A nasal gene signature identified in the study met the World Health Organization criteria for a TB triage test. Notably, among adults with TB, pathways related to the inflammatory response and innate immune system were down regulated in nasal samples and upregulated in blood, showing opposite directions between the two sample types.

These findings suggest nasal sampling could become a practical way to screen people with HIV for pulmonary TB. Because the study focused on ART-Naive adults in Uganda, it shows the approach can work in a real-world, high-need setting, but the authors emphasize that further validation is necessary. The proof-of-concept result—that nasal gene signatures can separate TB from non-TB in people living with HIV and that these signatures differ from blood—points to a new class of host-based biomarkers that can be collected with minimal discomfort. If confirmed in larger studies and in other difficult-to-diagnose groups, nasal transcriptomic tests could simplify triage, speed diagnosis, and prioritize who needs further TB testing or treatment. The researchers recommend additional validation studies of gene signatures using minimally invasive nasal samples to determine how well the approach performs across populations and clinical scenarios.