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Published online before print August 6, 2008
Eur Respir J 2008, doi:10.1183/09031936.00055508
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ORIGINAL ARTICLE

Evaluating the potential of IP-10 and MCP-2 as biomarkers for the diagnosis of TB

M. Ruhwald 1*, T. Bodmer 2, C. Maier 2, M. Jepsen 3, M.B. Andersen 4, J. Eugen-Olsen 4, P. Ravn , on behalf of TBNET

1 Dep. of Infectious Diseases 144, Copenhagen University, Hvidovre Hospital, 2650 Hvidovre, Denmark; and Clinical Research Centre 136, Copenhagen University, Hvidovre Hospital, 2650 Hvidovre, Denmark
2 Institute for Infectious Diseases, University of Bern, CH-3010 Bern, Switzerland
3 Dep. of Infectious Diseases 144, Copenhagen University, Hvidovre Hospital, 2650 Hvidovre, Denmark
4 Clinical Research Centre 136, Copenhagen University, Hvidovre Hospital, 2650 Hvidovre, Denmark

* To whom correspondence should be addressed. E-mail: mruhwald{at}mail.dk.


   Abstract

The aim of the study was to evaluate the potential of diagnostic tests based on IP-10 and MCP-2, and compare the performance with the Quantiferon-Gold In-Tube (QFT-IT) test.

IP-10 and MCP-2 were determined in supernatants from whole blood stimulated with M.tuberculosis-specific antigens. Samples were obtained from 80 patients with culture and/or PCR proven TB, and 124 unexposed healthy controls; 86 high school students and 38 high school staff. IP-10 and MCP-2 test cut-offs were established based on ROC curve analysis.

TB patients produced significantly higher levels of IP-10 (median 2158 pg·ml-1) and MCP-2 (median 379 pg·ml-1) compared with IFN-{gamma} (median 215 pg·ml-1, p<0.0001). The QFT-IT, IP-10 and MCP-2 tests detected 81%, 83% and 71% of the TB patients; 0%, 3% and 0% of the high school students and 0%, 16%; and 3% of the staff. Agreement between tests was high >89% (kappa>0.77). By combining IP-10 and IFN-{gamma} tests the detection rate increased among TB patients to 90% without a significant increase in positive responders among the students.

In conclusion, IP-10 and MCP-2 responses to M.tuberculosis specific antigens could be used to diagnose infection. Combining IP-10 and IFN-{gamma} may be a simple approach to increase the detection rate of the M.tuberculosis specific in-vitro tests.

Keywords:  Diagnosis, IGRA, IFN-{gamma}, tuberculosis, whole blood




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