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Mycobacterium tuberculosis-specific CD4 T-cell scoring discriminates tuberculosis infection from disease

Andrej Mantei,Tim Meyer,M. Schürmann,C. Beßler,H. Bias,D. Krieger,T. Bauer,P. Bacher,J. Helmuth,H. Volk,D. Schürmann,A. Scheffold,C. Meisel

Published 2022 in European Respiratory Journal

ABSTRACT

Background Rapid and reliable diagnostic work-up of tuberculosis (TB) remains a major healthcare goal. In particular, discrimination of TB infection from TB disease with currently available diagnostic tools is challenging and time consuming. This study aimed at establishing a standardised blood-based assay that rapidly and reliably discriminates TB infection from TB disease based on multiparameter analysis of TB antigen-reactive CD4+ T-cells acting as sensors for TB stage-specific immune status. Methods 157 HIV-negative subjects with suspected TB infection or TB disease were recruited from local tertiary care hospitals in Berlin (Germany). Peripheral blood mononuclear cells were analysed for CD4+ T-cells reactive to the Mycobacterium tuberculosis antigens purified protein derivative and early secretory antigenic target 6 kDa/culture filtrate protein 10. The activation state of TB antigen-reactive T-cells, identified by surface expression of CD154, was evaluated according to the expression profile of proliferation marker Ki-67 and activation markers CD38 and HLA-DR. Using data from 81 subjects with clinically confirmed TB infection (n=34) or culture-proven pulmonary or extrapulmonary TB disease (n=47), 12 parameters were derived from the expression profile and integrated into a scoring system. Results Using the scoring system, our assay (TB-Flow Assay) allowed reliable discrimination of TB infection from both pulmonary and extrapulmonary TB disease with high sensitivity (90.9%) and specificity (93.3%) as was confirmed by Monte-Carlo cross-validation. Conclusion With low time requirement, ease of sample collection, and high sensitivity and specificity both for pulmonary and extrapulmonary TB disease, we believe this novel standardised TB-Flow Assay will improve the work-up of patients with suspected TB disease, supporting rapid TB diagnosis and facilitating treatment decisions. In a prospective study, a scoring system based on analysis of the activation state of tuberculosis (TB)-specific CD4+ T-cells was developed that allows reliable discrimination of TB infection and TB disease with high sensitivity and specificity https://bit.ly/3EFG4KX

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