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

• Published in: Frontiers in immunology Vol. 11; p. 572620
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 09-09-2020
• Subjects: activation markers; cytokines; immunity; Immunology; treatment; tuberculosis; treatment; activation markers; cytokines; immunity; tuberculosis
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.572620

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.
Whole blood immune responses to
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.
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 (
= 0.0328 and
= 0.0400, respectively). Following PPD stimulation, slow treatment responders had a significantly higher proportion of CD8
CD27
IFN-γ
(
= 0.0105) and CD4
CD27
HLA-DR
CD38
(
= 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,
= 0.0156 and 0.84,
= 0.0102).
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.