Disease Extent And Anti-Tubercular Treatment Response Correlates With Mycobacterium Tuberculosis-Specific Cd4 T-Cell Phenotype Regardless Of Hiv-1 Status

Objectives The development of non-sputum-based assays for tuberculosis (TB) diagnosis and treatment monitoring is a key priority. Recent data indicate that whole blood-based assays to assess the phenotype ofMycobacterium tuberculosis(Mtb)-specific CD4 T cells hold promise for this purpose and require further investigation in well-characterised TB cohorts. In this study, we investigated the relationship between the phenotypic signature of Mtb-specific CD4 responses, TB disease extent and treatment response. Methods Using flow cytometry, we measured the expression of phenotypic and functional markers (HLA-DR, CD27, CD153, KLRG1, IL-2, MIP-1 beta, TNF-alpha and IFN-gamma) on Mtb-specific CD4 T-cells in whole blood from 161 participants of varying TB and HIV status. TB disease extent was graded as a continuum using the Xpert(ct)value, C-reactive protein, Timika radiographic score and monocyte/lymphocyte ratio. Results The phenotypic profile of Mtb-specific CD4 T cells pre-anti-tubercular treatment (ATT) strongly correlated with disease extent, irrespective of HIV status. ATT associated with major changes in the phenotype of Mtb-specific CD4 T cells, with decreased expression of HLA-DR and increased CD27 and CD153 expression. Principal component analysis showed an almost complete separation between latent TB infection (LTBI) and active TB (aTB) pre-ATT groups, whereas the profile of the aTB post-ATT group overlapped with the LTBI group. However, in patients experiencing treatment failure or relapse, no significant changes were observed in Mtb-specific CD4 T-cell phenotype pre- and post-ATT. Conclusion Whole blood-based assays of Mtb-specific CD4 T-cell activation and maturation markers can be used as non-sputum-based biomarkers of disease extent and treatment monitoring in TB, regardless of HIV-1 status.