Abstract
Currently available Interferon-γ release assay (IGRA) cannot reliably differentiate active TB (ATB) from non-active TB (non-ATB). A study was performed to evaluate the value of Mycobacterium tuberculosis (MTB) specific Th1 cell immune responses which test IFN-γ and IL-2 simultaneous for differentiating ATB from non-ATB. Forty-nine newly diagnosed inpatients with ATB (26 pulmonary TB and 23 extrapulmonary TB) were enrolled as the ATB group. Forty-five volunteers with latent tuberculosis infection (LTBI) and twenty with evidence of previous TB were enrolled during the same period as the non-ATB group. Clinical examination and MTB specific Th1 cell immune responses were performed for all participants. After being stimulated with ESAT-6 and CFP-10, the median frequencies of single IL-2-, single IFN-γ-, and dual IFN-γ/IL-2-secreting T-cells were all higher in the ATB group than in the non-ATB group (20(8–45) vs. 7(3–13), P<0.001;131(44–308) vs. 10(6–27), P<0.001;25(9–74) vs. 7(3–23), P = 0.001, respectively). Evaluation of the diagnostic performance of detecting single IFN-γ-secreting T cells for pulmonary TB employed a cutoff value of 35 iSFCs/250,000 PBMC. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were 92.3%, 80.0%, 64.9%, 96.3%, 4.62, and 0.10, respectively. For extrapulmonary TB, using a cutoff value of 23 iSFCs/ 250,000 PBMC, the sensitivity, specificity, PPV, NPV, PLR, and NLR were 91.3%, 76.9%, 58.3%, 96.2%, 3.96, and 0.11, respectively. When combining frequencies and proportion of single IFN-γ-secreting T cells, the test sensitivity was 100% in parallel tests and the specificity was 87.7% in serial tests for pulmonary TB. MTB specific Th1 cell immune responses (FluoroSpot) had value for the differentiation of ATB and non-ATB. Further confirmatory studies are indicated.
Highlights
In 2014,9.6 million people were estimated to have developed tuberculosis (TB) worldwide, with an incidence of 133/100000, and 1.5 million people died of TB[1]
Forty-nine patients with active TB (ATB) were included in the study, with 26 patients of smear-positive pulmonary TB (PTB), and 23 of EPTB.45 subjects with latent tuberculosis infection (LTBI) (24 without other diseases and 21 with other diseases) and 20 patients with evidences of previous TB were included in the study
After being stimulated with the antigens ESAT-6, CFP-10, or both the two antigens, frequencies of singleIL-2, single interferon γ (IFN-γ), and dual IFN-γ/interleukin 2 (IL-2)-secreting T-cells were all higher in the ATB group than in the non-ATB groups (P
Summary
In 2014,9.6 million people were estimated to have developed tuberculosis (TB) worldwide, with an incidence of 133/100000, and 1.5 million people died of TB[1]. According to WHO’s estimation, there were 930000 new TB cases in China in 2014, accounting for 10% of worldwide cases, following only India and Indonesia[1]. As tuberculin purified protein derivative (PPD) includes the common antigenic components of non-tuberculous mycobacterium and Bacillus CalmetteGuerin (BCG), the “false positive rate” is high in areas where vaccination of BCG is widely implemented[3]; while the sensitivity is low among immunocompromised individuals who are more susceptible to tuberculosis infection than the general population[4]
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