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Recruitment of mycobacterium tuberculosis specific CD4+ T cells to the site of infection for diagnosis of active tuberculosis

Journal of Internal Medicine, Volume 265, No. 1, Year 2009

Abstract. Nemeth J, Winkler H-M, Zwick RH, Rumetshofer R, Schenk P, Burghuber OC, Graninger W, Ramharter M, Winkler S (Medical University of Vienna, Vienna, Austria, Universitätsspital Basel, Basel, Switzerland, Otto-Wagner Hospital; Medical University of Vienna, Vienna; Austria). Recruitment of Mycobacterium tuberculosis specific CD4+ T cells to the site of infection for diagnosis of active tuberculosis. J Intern Med 2008; 265: 163-168.Context. Accurate and early diagnosis of active tuberculosis (TB) is problematic as current diagnostic methods show low sensitivity (acid-fast bacilli smears), are time-consuming (culture of biological samples) or show variable results [Mycobacterium tuberculosis (MTB)-specific PCR]. Objectives. In the course of infection, MTB-specific T cells clonally expand at the site of infection and may thus be used as diagnostic marker for active disease. Design. In this cohort study, the frequency of MTB-specific, interferon (IFN)-γ expressing CD4+ T cells obtained from peripheral blood and the site of disease in 25 patients with suspected TB was assessed (n = 11, bronchoalveolar lavage; n = 7, pleural fluid; n = 1, ascites; n = 1, joint fluid; n = 5, cerebrospinal fluid). Results. Amongst 15 patients who showed proven active TB infection, a striking increase of MTB-specific T cells was detected at the site of infection compared with peripheral blood (median increase: 28.5-fold, range: 7.25-531 fold; median of IFN-γ-producing CD4+ T cells from blood: 0.02%, range: 0-0.52%; median of IFN-γ-producing CD4+ T cells from the site of infection: 1.81%, range: 0.29-6.55%, P < 0.001). Main outcome measure. Recruitment of MTB-specific T cells to the site of infection yielded a sensitivity of 100% and specificity of 90%, irrespective of the compartment affected. Conclusions. The accumulation of MTB-specific T cells at the site of infection may prove as useful diagnostic marker for an accurate and rapid diagnosis of active TB. © 2008 Blackwell Publishing Ltd.
Statistics
Citations: 44
Authors: 6
Affiliations: 3
Research Areas
Health System And Policy
Infectious Diseases
Study Design
Cohort Study
Study Approach
Quantitative