Combined Antigen-Specific Interferon-γ and Interleukin-2 Release Assay (FluoroSpot) for the Diagnosis of Mycobacterium tuberculosis Infection

被引:13
作者
Chesov, Dumitru [1 ,2 ]
Lange, Christoph [2 ,3 ,4 ,5 ]
Daduna, Franziska [2 ,3 ]
Crudu, Valeriu [6 ]
Preyer, Rosemarie [7 ]
Ernst, Martin [8 ]
Kalsdorf, Barbara [2 ,3 ]
机构
[1] State Univ Med & Pharm Nicolae Testemitanu, Div Pneumol & Allergol, Kishinev, Moldova
[2] Res Ctr Borstel, Div Clin Infect Dis, Borstel, Germany
[3] German Ctr Infect Res, TB Unit, Borstel, Germany
[4] Med Univ Lubeck, Int Hlth Infect Dis, D-23538 Lubeck, Germany
[5] Karolinska Inst, Dept Med, Stockholm, Sweden
[6] Inst Phthisiopneumol Chiril Draganiuc, Lab Microbiol & Morphol TB, Kishinev, Moldova
[7] Autoimmun Diagnost GmbH, Strassberg, Germany
[8] Res Ctr Borstel, Div Immune Cell Analyt, Borstel, Germany
来源
PLOS ONE | 2015年 / 10卷 / 03期
关键词
T-CELL RESPONSES; TBNET CONSENSUS STATEMENT; LATENT TUBERCULOSIS; IFN-GAMMA; ACTIVE TB; IMMUNODIAGNOSIS; INDIVIDUALS; CYTOKINES; PROFILE; DISEASE;
D O I
10.1371/journal.pone.0120006
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background To evaluate interleukin (IL)-2 and interferon (IFN)-gamma secreting T-cells in parallel for the differentiation of latent infection with Mycobacterium tuberculosis infection (LTBI) from active tuberculosis. Methods Following ex-vivo stimulation of peripheral blood mononuclear cells (PBMC) with M. tuberculosis-specific antigens early secretory antigenic target (ESAT)-6 and culture filtrate protein (CFP)-10, immune responses were assessed by enzyme-linked immunospot IFN-. release assay (EliSpot-IGRA) and a novel dual cytokine detecting fluorescence-linked immunospot (FluoroSpot) in 18 patients with pulmonary tuberculosis, 10 persons with previously cured tuberculosis, 25 individuals with LTBI and 16 healthy controls. Results Correlation of IFN-gamma(+) spot-forming cells in EliSpot-IGRA and FluoroSpot were R-2 = 0.67 for ESAT-6 and R-2 = 0.73 for CFP-10. The number of IL-2-IFN-gamma(+) producing cells was higher in patients with tuberculosis compared with past tuberculosis (CFP-10-induced p = 0.0068) or individuals with LTBI (ESAT-6-induced p = 0.0136). A cutoff value of >16 CFP-10-induced IFN-gamma(+) secreting cells/200.000 PBMC in the EliSpot-IGRA discriminated with highest sensitivity and specificity (89% and 76%, respectively). However, overlap in cytokine responses precludes distinction between the cohorts on an individual basis. Conclusions Combined analysis of IFN-gamma and IL-2 secretion by antigen specific T-cells does not allow a reliable differentiation between different states of M. tuberculosis infection in clinical practice.
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页数:14
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