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Monitoring Anti-tuberculosis Treatment Response Using Analysis of Whole Blood Mycobacterium tuberculosis Specific T Cell Activation and Functional Markers

Article scientifique 2020 Anglais

Résumé

Background Blood-based biomarkers have been proposed as an alternative to current sputum-based treatment monitoring methods in active tuberculosis (ATB). The aim of this study was to validate previously described phenotypic, activation, and cytokine markers of treatment response in a West African cohort. Methods Whole blood immune responses to Mycobacterium tuberculosis ESAT-6/CFP-10 (EC) and purified protein derivative (PPD) were measured in twenty adults at baseline and after 2 months of standard TB treatment. Patients were classified as fast or slow responders based on a negative or positive sputum culture result at 2 months, respectively. Cellular expression of activation markers (CD38, HLA-DR), memory markers (CD27), and functional intracellular cytokine and proliferation (IFN-γ, Ki-67, TNF-α) markers were measured using multi-color flow cytometry. Results There was a significant increase in the proportion of CD4+CD27+ cells expressing CD38 and HLA-DR following EC stimulation at 2 months compared to baseline (p = 0.0328 and p = 0.0400, respectively). Following PPD stimulation, slow treatment responders had a significantly higher proportion of CD8+CD27–IFN-γ+ (p = 0.0105) and CD4+CD27+HLA-DR+CD38+ (p = 0.0077) T cells than fast responders at baseline. Receiver operating curve analysis of these subsets resulted in 80% sensitivity and 70 and 100% specificity, respectively (AUC of 0.82, p = 0.0156 and 0.84, p = 0.0102). Conclusion Our pilot data show reductions in expression of T cell activation markers were seen with treatment, but this was not associated with fast or slow sputum conversion at 2 months. However, baseline proportions of activated T cell subsets are potentially predictive of the subsequent speed of response to treatment.

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Vickers, M., Darboe, F., Muefong, C., Mbayo, G., Barry, A., Gindeh, A., Njie, S., Riley, A., Sarr, B., Sambou, B., Dockrell, H., Charalambous, S., Rachow, A., Owolabi, O., Jayasooriya, S., Sutherland, J. (2020). Monitoring Anti-tuberculosis Treatment Response Using Analysis of Whole Blood Mycobacterium tuberculosis Specific T Cell Activation and Functional Markers. https://doi.org/10.3389/fimmu.2020.572620

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Auteur(s)

Molly A. Vickers Fatoumatta Darboe Caleb Muefong Georgetta Mbayo Amadou Barry Awa Gindeh Sainabou Njie Abi-Janet Riley Binta Sarr Basil Sambou Hazel M. Dockrell Salome Charalambous Andrea Rachow Olumuyiwa Owolabi Shamanthi Jayasooriya Jayne S. Sutherland

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