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PLoS One. 2017 May 22;12(5):e0177850. doi: 10.1371/journal.pone.0177850. eCollection 2017.

Utility of Th1-cell immune responses for distinguishing active tuberculosis from non-active tuberculosis: A case-control study.

Zhang L1,2,3, Cheng X1, Bian S1, Song Y4, Li Q4, Gao M4, Zhang Y1, Shi X1,3, Liu X1,2,3.

Author information

1
Division of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
2
Clinical Epidemiology Unit, International Epidemiology Network, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China.
3
Centre for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
4
Tuberculosis Department, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.

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.

PMID:
28531231
PMCID:
PMC5439683
DOI:
10.1371/journal.pone.0177850
[Indexed for MEDLINE]
Free PMC Article

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