Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis

Background:The diagnosis of smear-negative pulmonary tuberculosis (TB) is problematic. There are limited data on the profile of alveolar TB antigen-specific T cells, and their utility for the rapid immunodiagnosis of pulmonary TB is unclear.Methods:Antigen-specific interferon γ (IFNγ) responses to t...

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Veröffentlicht in:	Thorax Jg. 64; H. 10; S. 847 - 853
Hauptverfasser:	Dheda, K, van Zyl-Smit, R N, Meldau, R, Meldau, S, Symons, G, Khalfey, H, Govender, N, Rosu, V, Sechi, L A, Maredza, A, Semple, P, Whitelaw, A, Wainwright, H, Badri, M, Dawson, R, Bateman, E D, Zumla, A
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London BMJ Publishing Group Ltd and British Thoracic Society 01.10.2009 BMJ Publishing Group BMJ Publishing Group LTD
Schlagworte:	Adult Antigens Antigens, Bacterial - metabolism Bacterial diseases Bacterial diseases of the respiratory system Bacteriological Techniques - methods Biological and medical sciences Biopsy Bronchoalveolar Lavage Fluid - immunology Cardiology. Vascular system Drug resistance Enzyme-Linked Immunosorbent Assay Female Histology HIV Human bacterial diseases Human immunodeficiency virus Humans Infections Infectious diseases Interferon-gamma - metabolism Lavage Lymphocytes Male Medical sciences Microscopy Mycobacterium tuberculosis - immunology Patients Pneumology T-Lymphocytes - immunology Tuberculosis Tuberculosis and atypical mycobacterial infections Tuberculosis, Pulmonary - diagnosis Tuberculosis, Pulmonary - immunology South Africa Cape Town South Africa Lung disease Respiratory disease Lung Pulmonary tuberculosis Cellular immunity Mycobacterial infection Infection Bacteriosis Anesthesia Circulatory system Diagnosis Cardiology Quantitative analysis
ISSN:	0040-6376, 1468-3296, 1468-3296
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Zusammenfassung:	Background:The diagnosis of smear-negative pulmonary tuberculosis (TB) is problematic. There are limited data on the profile of alveolar TB antigen-specific T cells, and their utility for the rapid immunodiagnosis of pulmonary TB is unclear.Methods:Antigen-specific interferon γ (IFNγ) responses to the RD-1 antigens ESAT-6 and CFP-10 (T-SPOT.TB and QuantiFERON-TB-Gold-In-Tube), heparin-binding haemagglutinin and purified protein derivative were evaluated, using alveolar lavage cells, in 91 consecutively recruited South African patients suspected of having TB.Results:Of 85 evaluable patients (29% HIV+), 24, 11, 48 and 2 had definite TB, probable TB, non-TB and an uncertain diagnosis, respectively. Between 34% (T-SPOT.TB) and 41% (QuantiFERON-TB-Gold-In-Tube) of all test results were inconclusive. Failure of the positive control was significantly higher with the QuantiFERON-TB-Gold-In-Tube than with T-SPOT.TB (85% vs 46% of inconclusive results; p = 0.001). Using staphylococcal enterotoxin B, compared with phytohaemagglutinin, substantially reduced failure of the positive control (25% to 3%; p = 0.02). In evaluable samples, when the definite and non-TB groups were used for outcome analysis, the percentage sensitivity, specificity, positive predictive value and negative predictive value for T-SPOT.TB (⩾20 spots/million alveolar mononuclear cells) and QuantiFERON-TB-Gold-In-Tube (0.35 IU/ml) were 89, 94, 89 and 94% (n = 55) and 55, 86, 77 and 69% (n = 46), respectively. Rapid diagnosis of TB was achieved more frequently with T-SPOT.TB than with smear microscopy (14/24 (58%) vs. 7/24 (29%) of definite TB cases; p = 0.02). Heparin-binding haemagluttinin and purified protein derivative alveolar lymphocyte IFNγ responses had poor performance outcomes.Conclusion:Provided evaluable results are obtained, the RD-1, but not the heparin-binding haemagglutinin or purified protein derivative, alveolar lymphocyte IFNγ ELISPOT response is a useful rapid immunodiagnostic test for TB. However, test utility in high-burden settings may be limited by the high proportion of inconclusive results.
Bibliographie:	istex:F179394F03BEE78B15C40DFE7F98E18B3321BB50 href:thoraxjnl-64-847.pdf local:thoraxjnl;64/10/847 PMID:19592392 ark:/67375/NVC-3T0K0QJQ-R ArticleID:tx116376 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Undefined-1 ObjectType-Feature-3 content type line 23
ISSN:	0040-6376 1468-3296 1468-3296
DOI:	10.1136/thx.2009.116376