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

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

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.572620

DOI=10.3389/fimmu.2020.572620

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>Whole blood immune responses to <italic>Mycobacterium tuberculosis</italic> 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.</p></sec><sec><title>Results</title><p>There was a significant increase in the proportion of CD4<sup>+</sup>CD27<sup>+</sup> cells expressing CD38 and HLA-DR following EC stimulation at 2 months compared to baseline (<italic>p</italic> = 0.0328 and <italic>p</italic> = 0.0400, respectively). Following PPD stimulation, slow treatment responders had a significantly higher proportion of CD8<sup>+</sup>CD27<sup>–</sup>IFN-γ<sup>+</sup> (<italic>p</italic> = 0.0105) and CD4<sup>+</sup>CD27<sup>+</sup>HLA-DR<sup>+</sup>CD38<sup>+</sup> (<italic>p</italic> = 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, <italic>p</italic> = 0.0156 and 0.84, <italic>p</italic> = 0.0102).</p></sec><sec><title>Conclusion</title><p>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.</p></sec>