Raphael Kamng'ona Poster 2025

Mr Raphael Kamng'ona

MRC Unit The Gambia at LSHTM, The Gambia

Analysis of Immune cells and pathways in the development and outcome of post-TB lung disease

Poster Abstract

Background: Post-Tuberculosis Lung Disease (PTLD) affects nearly 50% of tuberculosis (TB) survivors, leading to chronic morbidity and impaired lung function. PTLD arises from unresolved inflammation and immune dysregulation persisting after Mycobacterium tuberculosis (Mtb) clearance. PTLD remains underexplored despite its growing burden.

Aims: This study aims to investigate immune cell pathways and mechanisms driving PTLD progression. Specific objectives include (1) profiling immune cells and cytokine dynamics in blood and bronchoalveolar lavage (BAL) samples from TB survivors, (2) identifying predictive biomarkers for different PTLD stages, and (3) uncovering therapeutic targets for host-directed therapies (HDTs) to mitigate long-term lung impairment.

Methods: Blood and BAL samples were obtained from TB survivors enrolled in the TB Sequel II cohort (parent study) in The Gambia between 4-7 years post-treatment. Participants were grouped based on clinical assessment (e.g. spirometry score, CT scans) into fully recovered, mild lung impairment, severe lung impairment, and exacerbation. Techniques, including flow cytometry, single-cell RNA sequencing (scRNA-seq), and multiplex cytokine profiling, will be employed to assess immune cell subsets, cytokine profiles, and immune signatures associated with PTLD.

Preliminary Results: Initial flow-cytometry findings from exacerbation group reveal a predominant exhausted memory phenotype (CD27-CD45RO-, p=0.0001), alongside reduced FOXP3+ regulatory T cells (p=0.001) in the lung compared to blood. Higher frequency of mono-functional TNF-α+ T-cells (p=0.0004) were detected in the lung than in blood following TB antigen-stimulation, highlighting persistent localized inflammation. Furthermore, lung neutrophils were predominantly activated (CD16+CD62L-, p=0.004) and exhausted (CD16 -CD62L-, p=0.0001) as compared to blood, suggesting persistent inflammation.

Conclusion: These findings suggest that lung T cells and neutrophils exhibit exhausted phenotypes associated with chronic pathology and exacerbation in PTLD. Identifying immune mechanisms and novel biomarkers will guide the development of host-directed therapies to improve lung function in PTLD and enhance the quality of life for TB survivors worldwide.

Biography

Raphael Kamng’ona is a passionate immunologist focused on advancing research into infectious diseases in Africa. He holds a Bachelor of Education in Biology and Chemistry from the University of Malawi and a Master’s in Immunology from the University of Glasgow, completed under a Chevening Scholarship. Currently pursuing a PhD at MRC Unit The Gambia at LSHTM, Raphael focuses on immune dysregulation in post-TB lung disease. Previously, he served as a Research Associate at the Malawi-Liverpool-Wellcome Trust, contributing to pioneering studies on pneumococcal infections. Raphael also mentors young scientists and leads the I Can Foundation, promoting youth education and career development.