Blood-based immunological signatures for extrapulmonary tuberculosis decoded
First biomarkers for rapid diagnosis and targeted therapy
Development of targeted therapeutics and diagnostics for extrapulmonary tuberculosis at University Hospital Cologne.
Tuberculosis (TB) 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 from the German Center for Infection Research (DZIF), the German Center for Neurodegenerative Diseases (DZNE), the University Hospital Cologne, and the LIMES Institute at the University of Bonn 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 from the German Center for Infection Research (DZIF), the German Center for Neurodegenerative Diseases (DZNE), the LIMES Institute at the University of Bonn, and the University Hospital Cologne 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.
Classification into immunotypes provides new insights into disease mechanisms
"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 Dr. Sebastian Theobald, first author and research associate at the University Hospital Cologne. "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 Prof. Jan Rybniker, Head of the Division of Infectious Diseases at University Hospital Cologne and Deputy Coordinator of the DZIF Research Area Tuberculosis. "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 Kilian Dahm, co-first author and bioinformatician at the University Hospital Bonn and the DZNE.
New diagnostics thanks to molecular signatures in blood
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 Dr. Thomas Ulas, a bioinformatician at the DZNE and the LIMES Institute at the University of Bonn. "The clinical characterization of the patients was crucial in order to correctly classify the molecular results and bridge the gap to clinical application," adds PD Dr. Isabelle Suárez, senior physician at Clinic I for Internal Medicine at University Hospital Cologne.
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, led by Prof. Jan Rybniker and PD Dr. Isabelle Suárez at several DZIF partner sites in Germany.
