Multi-parameter flow cytometry immunophenotyping distinguishes different stages of tuberculosis infection - 26/07/20
Highlights |
• | Active TB patients have higher Monocyte-to-lymphocyte and Neutrophil-to-lymphocyte ratios than latent TB and NoTBI contacts. |
• | Active TB patients are characterized by lower Th1/Th2 ratio and lower proportion of Th1-Th17, CD4+ central memory and MAIT cells. |
• | CD154 expression is higher in Mtb-stimulated central and effector memory CD4+ T cells from active and latent TB than NoTBI contacts. |
• | Expression of CD154 showed a higher accuracy than production of IFNγ to discriminate Mtb-specific activation in CD4+ T cells. |
• | Other candidate cell subsets to discriminate between TB study groups include γδ CD56+, NK-Bright and CD8+ T cells. |
Summary |
Objectives |
To identify new potential host biomarkers in blood to discriminate between active TB patients, uninfected (NoTBI) and latently infected contacts (LTBI).
Methods |
A blood cell count was performed to study parent leukocyte populations. Peripheral blood mononuclear cells (PBMCs) were isolated and a multi-parameter flow cytometry assay was conducted to study the distribution of basal and Mycobacterium tuberculosis (Mtb)-stimulated lymphocytes. Differences between groups and the area under the ROC curve (AUC) were investigated to assess the diagnostic accuracy.
Results |
Active TB patients presented higher Monocyte-to-lymphocyte and Neutrophil-to-lymphocyte ratios than LTBI and NoTBI contacts (p<0.0001; AUC>0.8). Lymphocyte subsets with differences (p >0.05; AUC >0.7) between active TB and both contact groups include the basal distribution of Th1/Th2 ratio, Th1-Th17, CD4+ Central Memory (TCM) or MAIT cells. Expression of CD154 is increased in Mtb-activated CD4+ TCM and Effector Memory T cells in active TB and LTBI compared to NoTBI. In CD4+ T cells, expression of CD154 showed a higher accuracy than IFNγ to discriminate Mtb-specific activation.
Conclusions |
We identified different cell subsets with potential use in tuberculosis diagnosis. Among them, distribution of CD4 TCM cells and their expression of CD154 after Mtb-activation are the most promising candidates.
Le texte complet de cet article est disponible en PDF.Keywords : Tuberculosis, Immunophenotype, TB diagnosis, Blood cells biomarkers, Flow cytometry
Plan
Vol 81 - N° 1
P. 57-71 - juillet 2020 Retour au numéro
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