Biomarker Research

Biomarker Discovery for Diagnostic and Prognostic Purposes

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At the UGH, we are searching for biomarkers to predict the development of respiratory diseases and infections and to monitor the treatment of patients with these conditions. Through collaborations with various international tuberculosis and lung health research networks, the UGH has access to globally representative biospecimens from clinically well-characterised patients. The research methods used at the UGH include classical immunological methods such as immunophenotyping and cytokine analysis, complemented by novel techniques such as genomics, proteomics and single-cell multi-omics analyses.

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Cellular immunology

The immune response to Tuberculosis (TB) involves a complex interplay of various immune cells, cytokines, and molecular pathways. In post TB lung disease (PTLD), the immune system´s continued involvement is critical in determining the extent of tissue repair, resolution of inflammation, and susceptibility to recurrent infections.

Multiple cell types are implicated in the control of M.tb infections, however, dysregulation can lead to excessive lung damage. Our research focuses on neutrophil and T-cell responses during active TB and post-TB treatment phase, revealing the significant roles of neutrophils, oxidative stress, and their mediators not only in M.tb defence mechanism but also in PTLD development.

Our findings also suggest that spikes in M.tb-specific T-cell activity in TB survivors might coincide with exacerbations in lung impairment and renewed M.tb activity. In a next step we want to uncover the clinical implications of immune dysregulation of neutrophils and prolonged immune activation post-TB treatment and its association with specific lung pathologies and PTLD phenotypes.

Multi-omics analyses

Over the past two decades, numerous transcriptomic and proteomic host-response signatures associated with TB have emerged, enhancing our understanding of TB progression and treatment response, and showing diagnostic potential with high sensitivity and specificity. However, multi-omic analyses related to post-tuberculosis lung function and pathology (PTLD) are still lacking, and no PTLD-specific signatures have been identified until today. Our primary whole blood mRNA-sequencing studies revealed that the regulation of transcriptional pathways related to cellular development, differentiation, and humoral immune responses is different in patients who develop post TB lung damage compared to those without lung pathologies after TB. Our research also highlighted the differential regulation of neutrophil-related genes and oxidative stress pathways, aligning with the results of our HDT trials and related cellular immunity work.

Building on these results, we now aim to perform targeted transcriptomic analyses of up to 500 genes in several PTLD cohorts globally. Considering that typical changes in lung function in PTLD are also observed in patients with chronic airways disease such as asthma and COPD, our approach will also include genes identified in the previous analysis as well as signature genes associated with COPD and asthma.

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