Disease extent and anti-tubercular treatment response correlates with Mycobacterium tuberculosis -specific CD4 T-cell phenotype regardless of HIV-1 status.

Autor: Riou C; Wellcome Centre for Infectious Disease Research in Africa Institute of Infectious Disease and Molecular Medicine University of Cape Town Observatory South Africa.; Division of Immunology Department of Pathology University of Cape Town Observatory South Africa., Du Bruyn E; Wellcome Centre for Infectious Disease Research in Africa Institute of Infectious Disease and Molecular Medicine University of Cape Town Observatory South Africa., Ruzive S; Wellcome Centre for Infectious Disease Research in Africa Institute of Infectious Disease and Molecular Medicine University of Cape Town Observatory South Africa., Goliath RT; Wellcome Centre for Infectious Disease Research in Africa Institute of Infectious Disease and Molecular Medicine University of Cape Town Observatory South Africa., Lindestam Arlehamn CS; Division of Vaccine Discovery La Jolla Institute for Immunology La Jolla CA USA., Sette A; Division of Vaccine Discovery La Jolla Institute for Immunology La Jolla CA USA.; Department of Medicine University of California San Diego La Jolla CA USA., Sher A; Immunobiology Section Laboratory of Parasitic Diseases National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD USA., Barber DL; T Lymphocyte Biology Section Laboratory of Parasitic Diseases National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD USA., Wilkinson RJ; Wellcome Centre for Infectious Disease Research in Africa Institute of Infectious Disease and Molecular Medicine University of Cape Town Observatory South Africa.; Department of Infectious Diseases Imperial College London London UK.; Department of Medicine University of Cape Town Observatory South Africa.; The Francis Crick Institute London UK.
Jazyk: angličtina
Zdroj: Clinical & translational immunology [Clin Transl Immunology] 2020 Sep 28; Vol. 9 (9), pp. e1176. Date of Electronic Publication: 2020 Sep 28 (Print Publication: 2020).
DOI: 10.1002/cti2.1176
Abstrakt: 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 of Mycobacterium 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-1β, TNF-α and IFN-γ) 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.
Competing Interests: The authors declare no conflict of interest.
(© 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)
Databáze: MEDLINE
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