Fatoumatta Darboe Poster 2024

Fatoumatta Darboe

Fatoumatta Darboe,

University of California San Francisco (UCSF), USA

Immune pathogenesis of TB disease and impact of HIV infection on risk of TB disease progression 


Poster Abstract

BACKGROUND: Systemic hyperinflammation is a characteristic feature of TB disease. The study is based on the hypothesis that excessive and prolonged systemic inflammation associated with tuberculosis may be a major contributor for inflammaging and immunosenescence in cured TB patients, resulting in increased mortality and morbidity.

METHODS: The study population included two groups (BCG vaccinated at birth) of individuals aged between 18 and 59 years, namely previously treated and cured TB patients (Group 1) and healthy controls (group 2) with no prior history of TB matched for age, sex and lifestyle with group 1 participants. Data from 30 participants in each group was used for this analysis. Peripheral Blood Mononuclear Cells (PBMCs) were isolated from whole blood and used to measure β-galactosidase, telomere length and expression of IFNg, CD57 and CD28. Graphpad prism was used to compute statistical significance. P<0.05 was considered to be statistically significant.

RESULTS: CD8 cells and CD4 cells from group 1 had significantly increased expression of senescence marker CD57 (p=0.0215) and IFNg (p=0.04) respectively as compared to Group 2. Meanwhile, the proportion of CD8 cells expressing CD28 (p=0.082) was significantly decreased in group 1 in comparison to group 2. β-galactosidase assay was done to measure cellular senescence in the study groups which showed significantly increased SA-β-gal activity in group 1 as compared to group 2 (p=0.001). We also observed a significant decrease in the length of telomeres of PBMCs in group 1 (2-3 kb) compared to group 2 (5-15kb) (p=0.0358).

INFERENCE: The preliminary findings of the study like increased beta galactosidase activity, increased expression of senescence markers like CD57 and CD28 and reduced telomere length are clearly suggestive of accelerated immune senescence and premature onset of aging in cured TB patients. As BCG is proven to reduce immune senescence and inflammation (Kumar et al., 2021), BCG revaccination could plausibly reduce immune senescence in such individuals.