Hidden inflammation: asymptomatic tuberculosis shares blood signatures with symptomatic disease

Tuberculosis (TB) is often thought of as a disease with clear symptoms, but a large proportion of people carrying Mycobacterium tuberculosis show no symptoms at all. Those asymptomatic infections can still spread disease and may progress to active illness, yet their biological and inflammatory characteristics are poorly understood. In a study led by corresponding author Thomas J. Scriba, researchers set out to compare the blood profiles of people identified through South African community screening with those who presented to health facilities for TB triage. By studying blood at the level of gene expression (transcriptomics) and circulating proteins (proteomics), the team aimed to map whether asymptomatic TB shares the same immune signatures as symptomatic TB or represents a different biological state. The work compared two kinds of real-world cohorts—community-screened individuals and people seeking care—and used integrated analysis of both transcriptomic and proteomic data to look for patterns that might reveal how the immune system reacts in patients without symptoms.

The researchers characterized blood transcriptomic and proteomic profiles in South African community screening versus health facility-based triage cohorts. They found that asymptomatic TB shared core transcriptomic and proteomic features with symptomatic TB, including upregulation of innate, interferon and inflammatory pathways and downregulation of T and B cell pathways. When transcriptomic and proteomic data from people with asymptomatic TB were combined, two distinct sub-clusters emerged. These sub-clusters differed by higher or lower bacterial burden, blood IFN-γ responses, body mass index (BMI), and chest radiographic abnormalities, suggesting different degrees of disease severity among people without symptoms. The team also identified a new blood transcriptomic signature specific to asymptomatic TB. However, the diagnostic performance of transcriptomic and proteomic markers was weaker for asymptomatic TB than for symptomatic TB, indicating that tools developed for triage in clinics may underperform when used for community-based screening.

These findings matter because they show both commonality and important differences between asymptomatic and symptomatic TB. On one hand, shared inflammatory and interferon-driven signals indicate that even silent infections trigger core immune responses that are detectable in blood. On the other hand, the existence of two subgroups within asymptomatic TB—distinguished by bacterial load, IFN-γ response, BMI and radiographic changes—highlights that asymptomatic TB is not a single uniform state. Practically, this means public health programs aiming to screen communities cannot simply repurpose biomarkers designed for symptomatic patients and expect the same accuracy. Instead, the new asymptomatic transcriptomic signature offers a starting point for tests tailored to community screening, but it will need further validation and optimization before it can guide policy or replace current triage approaches. The study underscores the need for targeted biomarker development to detect and stratify asymptomatic TB more reliably.