Specific T-cell epitopes for immunoassay-based diagnosis of Mycobacterium tuberculosis infection

被引:107
作者
Brock, I
Weldingh, K
Leyten, EMS
Arend, SM
Ravn, P
Andersen, P
机构
[1] Statens Serum Inst, Dept Infect Dis Immunol, DK-2300 Copenhagen S, Denmark
[2] Hvidovre Univ Hosp, Dept Infect Dis, Copenhagen, Denmark
[3] Leiden Univ, Ctr Med, Dept Infect Dis, Leiden, Netherlands
[4] Leiden Univ, Ctr Med, Dept Immunohematol & Blood Transfus, Leiden, Netherlands
关键词
D O I
10.1128/JCM.42.6.2379-2387.2004
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The currently used method for immunological detection of tuberculosis infection, the tuberculin skin test, has low specificity. Antigens specific for Mycobacterium tuberculosis to replace purified protein derivative are therefore urgently needed. We have performed a rigorous assessment of the diagnostic potential of four recently identified antigens (Rv2653, Rv2654, Rv3873, and Rv3878) from genomic regions that are lacking from the Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccine strains as well as from the most common nontuberculous mycobacteria. The fine specificity of potential epitopes in these molecules was evaluated by sensitive testing of the T-cell responses of peripheral blood mononuclear cells derived from M. bovis BCG-vaccinated healthy individuals to synthesized overlapping peptides. Three of the four molecules contained regions with significant specificity problems (Rv2653, Rv3873, and Rv3878). We selected and combined the specific peptide stretches from the four proteins not recognized by M. bovis BCG-vaccinated individuals. These peptide stretches were tested with peripheral blood mononuclear cells obtained from patients with microscopy or culture-confirmed tuberculosis and from healthy M. bovis BCG-vaccinated controls. The combination of the most promising stretches from this analysis showed a sensitivity level (57%) comparable to the level found with the two well-known M. tuberculosis-specific proteins ESAT-6 and CFP-10 (75 and 66%, respectively). The combination of ESAT-6, CFP-10, and the novel specific peptide stretches gave an overall sensitivity of 84% at a specificity of 97%. In a validation experiment with new experimental groups, the sensitivities obtained were 57% for the combination of peptides and 90% for the combination of the peptides, ESAT-6, and CFP-10. This combination gave a specificity of 95%.
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收藏
页码:2379 / 2387
页数:9
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