Blood-based immunological signatures for extrapulmonary tuberculosis
Tuberculosis is one of the world's leading infectious diseases. Infection with the bacterium Mycobacterium tuberculosis primarily affects the lungs, but in up to 25 percent of all infected individuals, it also affects other parts of the body, such as the lymph nodes, bones, or brain.
In a study published today in the renowned journal Nature Communications, researchers have deciphered the immunological properties of extrapulmonary tuberculosis (EPTB) in the blood of affected patients. The results may help to develop new targeted treatments and tests for this important disease.
Around ten million people contract tuberculosis (TB) every year, and 1.25 million people die from the infection. However, the immune response to TB, especially extrapulmonary TB (EPTB), is still not well understood. EPTB affects up to 30 percent of patients in some regions of the world and can affect any organ other than the lungs. This complicates diagnosis and treatment, as there are no easily accessible biomarkers.
To better understand the immunological processes driving EPTB, researchers examined the blood of EPTB patients using state-of-the-art multi-omics approaches, including single-cell RNA sequencing of blood cells. Analysis of the transcriptome data revealed complex signaling networks between components of the immune system that play an important role in fighting pathogens and regulating inflammation.
"With the help of the data, we were able to assign EPTB patients to three clearly distinguishable immunotypes for the first time, which reflect different disease courses," says the first author. "This dynamic provides new insights into the disease mechanism of tuberculosis and will hopefully enable us to treat patients individually and more effectively in the future," adds the senior author. "In particular, the interaction of the interferon and interleukin-1 signaling pathways and the activation of T cells and natural killer cells played a key role in identifying the immunotypes," says a co-first author.
In addition, the researchers succeeded in developing gene expression-based biomarkers that can reliably diagnose both extrapulmonary and pulmonary tuberculosis. Currently, patients must undergo a tissue biopsy to diagnose EPTB. In the future, the determination of signatures based on immunological markers and gene expression patterns in the blood could serve as easily accessible biomarkers for the diagnosis of EPTB, thus having a significant impact on patient care.
"These findings have the potential to substantially advance the diagnosis and treatment of tuberculosis and to facilitate the development of targeted, personalized therapies," says another author. "The clinical characterization of the patients was crucial in order to correctly classify the molecular results and bridge the gap to clinical application," adds another author.
The findings from the investigation of molecular signatures in the blood of EPTB patients are currently being further validated in a larger clinical cohort, the mEX-TB study.
