1. Monitoring Anti-tuberculosis Treatment Response Using Analysis of Whole Blood Mycobacterium tuberculosis Specific T Cell Activation and Functional Markers
- Author
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Molly A. Vickers, Fatoumatta Darboe, Caleb N. 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, and Jayne S. Sutherland
- Subjects
lcsh:Immunologic diseases. Allergy ,Adult ,CD4-Positive T-Lymphocytes ,Male ,0301 basic medicine ,Tuberculosis ,T cell ,Immunology ,Antitubercular Agents ,CD8-Positive T-Lymphocytes ,CD38 ,Lymphocyte Activation ,Biomarkers, Pharmacological ,Sputum culture ,Mycobacterium tuberculosis ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,T-Lymphocyte Subsets ,medicine ,Humans ,Immunology and Allergy ,activation markers ,Original Research ,Whole blood ,treatment ,medicine.diagnostic_test ,biology ,business.industry ,biology.organism_classification ,medicine.disease ,immunity ,cytokines ,Tumor Necrosis Factor Receptor Superfamily, Member 7 ,030104 developmental biology ,medicine.anatomical_structure ,tuberculosis ,030220 oncology & carcinogenesis ,Sputum ,Female ,medicine.symptom ,lcsh:RC581-607 ,business ,CD8 - Abstract
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.
- Published
- 2020
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