Stratified Threshold Values of QuantiFERON Assay for Diagnosing Tuberculosis Infection in Immunocompromised Populations

Background. The detection of latent tuberculosis (TB) is essential for TB control, but T-cell assay might be influenced by degree of immunosuppression. The relationship between immunocompetence and interferon (IFN)-γ response in QuantiFERON-TB Gold (QFT) is uncertain, especially in HIV-negative populations. Methods and Results. QFT has been performed for healthy subjects and TB suspected patients. Of 3017 patients, 727 were diagnosed as pulmonary TB by culture. The absolute number of blood lymphocyte in TB patients was significantly associated with QFT. Definitive TB patients were divided into eight groups according to lymphocyte counts. For each subgroup, receiver operating characteristic curve analysis was conducted from 357 healthy control subjects. The optimal cut-off for the patient group with adequate lymphocyte counts was found, but this was reduced for lymphocytopenia. Conclusions. The lymphocyte count was positively associated with QFT. Positive criteria should be calibrated in consideration of cell-mediated immunocompetence and risk of progression to active TB

Clinical Study Stratified Threshold Values of QuantiFERON Assay for Diagnosing Tuberculosis Infection in Immunocompromised Populations

Background. The detection of latent tuberculosis (TB) is essential for TB control, but T-cell assay might be influenced by degree of immunosuppression. The relationship between immunocompetence and interferon (IFN)-γ response in QuantiFERON-TB Gold (QFT) is uncertain, especially in HIV-negative populations. Methods and Results. QFT has been performed for healthy subjects and TB suspected patients. Of 3017 patients, 727 were diagnosed as pulmonary TB by culture. The absolute number of blood lymphocyte in TB patients was significantly associated with QFT. Definitive TB patients were divided into eight groups according to lymphocyte counts. For each subgroup, receiver operating characteristic curve analysis was conducted from 357 healthy control subjects. The optimal cut-off for the patient group with adequate lymphocyte counts was found, but this was reduced for lymphocytopenia. Conclusions. The lymphocyte count was positively associated with QFT. Positive criteria should be calibrated in consideration of cell-mediated immunocompetence and risk of progression to active TB

Multicolor Flow Cytometric Analyses of CD4+ T Cell Responses to Mycobacterium tuberculosis-Related Latent Antigens

Although IFN-γ release assays (IγRAs) provide increased specificity over tuberculin skin tests, the early and sensitive detection of reactivation of latently infected Mycobacterium tuberculosis is required to control tuberculosis (TB). Recently, a multicolor flow cytometry has been developed to study CD4+ T cell cytokine responses (IFN-γ/IL-2/TNF-a) to purified protein derivatives (PPD) and M. tuberculosis-specific antigens (ESAT-6/CFP-10) and provided useful information regarding anti-TB immunity. However, the diagnostic relevancy remains uncertain. Here, we analyzed three additional CD4+ T cell cytokine responses (IL-10/IL-13/IL-17) to latent mycobacterial antigens (a-crystallin, methylated heparin-binding hemagglutinin [HBHA], and mycobacterial DNA-binding protein 1 [MDP-1]) as well as PPD and ESAT-6/CFP-10 in 12 IGRA+ TB cases and 8 healthy controls. No significant difference in IFN-γ response was observed between TB cases and controls, which was likely due to the high variation among the individuals. However, we found a significant increase over healthy controls in (i) the IL-2 response to HBHA in recovery stage TB cases, (ii) the number of M. tuberculosisspecific polyfunctional CD4+ T cells in on-treatment and recovery stage cases, and (iii) the IL-17 response to HBHA and MDP-1 in on-treatment and recovery stage cases. These results suggest that a combination of these T cell cytokine parameters could aid in accurate diagnosis of latent TB infection