Mycobacterium tuberculosis antigen-specific T-cell responses in smear-negative pulmonary tuberculosis patients.
Ahmed EsmaelTamrat AbebeAdane MihretDaniel MussaSebsib NewayJoel ErnstJyothi RengarajanLiya WassieRawleigh HowePublished in: Clinical and experimental immunology (2022)
Despite recent improvements in microbial detection, smear-negative TB remains a diagnostic challenge. In this study, we investigated the potential discriminatory role of polychromatic flow cytometry of M. tuberculosis antigen-specific T cells to discriminate smear-negative TB from health controls with or without latent TB infection, and non-TB respiratory illnesses in an endemic setting. A cross-sectional study was conducted on HIV negative, newly diagnosed smear-positive PTB (n = 34), smear-negative/GeneXpert negative PTB (n = 29) patients, non-TB patients with respiratory illness (n = 33) and apparently healthy latent TB infected (n = 30) or non-infected (n = 23) individuals. The expression of activation (HLA-DR, CD-38), proliferation (Ki-67), and functional (IFN-γ, TNF-α) T-cell markers using polychromatic flow cytometry was defined after stimulation with PPD antigens. Sputum samples were collected and processed from all patients for Mtb detection using a concentrated microscopy, LJ/MGIT culture, and RD9 typing by PCR. Our study showed CD4 T cells specific for PPD co-expressed activation/proliferation markers together with induced cytokines IFN-γ or TNF-α were present at substantially higher levels among patients with smear-positive and smear-negative pulmonary TB than among healthy controls and to a lesser extent among patients with non-TB illness. Our study conclude that smear-negative TB can be distinguished from non-TB respiratory illness and healthy controls with a flow cytometric assay for PPD-specific T cells co-expressing activation/proliferation markers and cytokines.
Keyphrases
- pulmonary tuberculosis
- mycobacterium tuberculosis
- newly diagnosed
- end stage renal disease
- flow cytometry
- chronic kidney disease
- ejection fraction
- rheumatoid arthritis
- peritoneal dialysis
- healthcare
- high throughput
- signaling pathway
- dendritic cells
- public health
- hiv infected
- mass spectrometry
- high resolution
- squamous cell carcinoma
- pulmonary hypertension
- immune response
- risk assessment
- patient reported
- locally advanced
- single cell
- electronic health record
- hepatitis c virus
- oxidative stress
- diabetic rats
- rectal cancer
- south africa
- high speed