%A Vickers,Molly A.
%A Darboe,Fatoumatta
%A Muefong,Caleb N.
%A Mbayo,Georgetta
%A Barry,Amadou
%A Gindeh,Awa
%A Njie,Sainabou
%A Riley,Abi-Janet
%A Sarr,Binta
%A Sambou,Basil
%A Dockrell,Hazel M.
%A Charalambous,Salome
%A Rachow,Andrea
%A Owolabi,Olumuyiwa
%A Jayasooriya,Shamanthi
%A Sutherland,Jayne S.
%D 2020
%J Frontiers in Immunology
%C
%F
%G English
%K Tuberculosis,Treatment,Activation markers,Cytokines,Immunity
%Q
%R 10.3389/fimmu.2020.572620
%W
%L
%M
%P
%7
%8 2020-September-09
%9 Original Research
%#
%! TB treatment response markers
%*
%<
%T Monitoring Anti-tuberculosis Treatment Response Using Analysis of Whole Blood Mycobacterium tuberculosis Specific T Cell Activation and Functional Markers
%U https://www.frontiersin.org/articles/10.3389/fimmu.2020.572620
%V 11
%0 JOURNAL ARTICLE
%@ 1664-3224
%X BackgroundBlood-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.MethodsWhole 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.ResultsThere 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).ConclusionOur 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.