Cargando…

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

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-bas...

Descripción completa

Detalles Bibliográficos
Autores principales: Mantei, Andrej, Meyer, Tim, Schürmann, Mariana, Beßler, Christiane, Bias, Harald, Krieger, David, Bauer, Torsten, Bacher, Petra, Helmuth, Johannes, Volk, Hans-Dieter, Schürmann, Dirk, Scheffold, Alexander, Meisel, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: European Respiratory Society 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329623/
https://www.ncbi.nlm.nih.gov/pubmed/35618277
http://dx.doi.org/10.1183/13993003.01780-2021
Descripción
Sumario: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.