Differential expression of activation markers by Mycobacterium tuberculosis-specific CD4+ T-cell distinguishes extrapulmonary from pulmonary tuberculosis and latent infection

Background:

The diagnosis of active tuberculosis (ATB) currently depends on microbiological and molecular tests to detect Mycobacterium tuberculosis (Mtb). However, these methods have low sensitivity in extrapulmonary TB (EPTB) due to low bacillary burden. While previous studies identified CD38, HLADR, and Ki67 on Mtb-specific CD4+ T-cells as markers for identifying ATB and distinguishing it from latent TB infection (LTBI) in pulmonary cases, their performance in EPTB has not been fully explored.

Abstract:

Methods: A case-control study was performed using discriminant analyses in 270 Brazilian individuals to validate the use of Mtb-specific CD4+ T-cell activation markers (CD38, HLADR, and Ki67) in distinguishing ATB (PTB and EPTB) from LTBI, as well as EPTB from PTB. Frequencies of these markers were assessed by flow cytometry.

Results: Patients with EPTB and PTB exhibited significantly higher frequencies of CD4+ T-cells expressing CD38, HLADR, or Ki67 compared to those with LTBI ($p < 0.001$). Notably, the frequencies of HLADR ($p = 0.03$) and Ki67 ($p < 0.001$) were even higher in EPTB than in PTB patients, allowing for accurate discrimination between these clinical forms. HIV co-infection did not negatively impact the diagnostic accuracy of these markers.

Conclusion: Activation markers on Mtb-specific CD4+ T-cells are reliable blood-based biomarkers for identifying active TB and distinguishing between pulmonary and extrapulmonary manifestations, regardless of HIV status.

Keywords: tuberculosis, biomarker, extrapulmonary TB, T-cells, immune activation.

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• Data de Publicação: 06/11/2019
• Autores: Paulo S. Silveira-Mattos1,2,3 , Beatriz Barreto-Duarte1,2,4 , Beatriz Vasconcelos1,2,5 , Kiyoshi F. Fukutani1,2,3 , Caian L. Vinhaes1,2,3, Deivide Oliveira-de-Souza1,2,3 , Chris C. Ibegbu6,7 , Marina C. Figueiredo8 , Timothy R. Sterling8 *, Jyothi Rengarajan6,7 * and Bruno B. Andrade1,2,3,4,5,8,9*