Mycobacterium tuberculosis-specific CD4 T-cell scoring discriminates tuberculosis infection from disease.
Authors
Andrej Mantei, Tim Meyer, Mariana Schürmann, Christiane Beßler, Harald Bias, David Krieger, Torsten Bauer, Petra Bacher, Johannes Helmuth, Hans-Dieter Volk, Dirk Schürmann, Alexander Scheffold, Christian Meisel
Year of publication
2022Journal
EUR RESPIR JVolume
-Issue
-Abstract
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 disease based on multiparameter analysis of TB antigen-reactive CD4+ T cells acting as sensors for the TB stage-specific immune status.A total of 157 HIV-negative subjects suspected with TB infection or disease was recruited from local tertiary care hospitals. Peripheral blood mononuclear cells were analysed for CD4+ T cells reactive to the Mycobacterium tuberculosis antigens PPD and ESAT-6/CFP-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) twelve parameters were derived from the expression profile and integrated into a scoring system.Using the scoring system our 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.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.