Clinical application of a rapid lung-orientated immunoassay in individuals with possible tuberculosis

R. A. M. Breen, S. M. Barry, C. J. Smith, R. J. Shorten, J. P. Dilworth, I. Cropley, T. D. McHugh, Stephen Henry Gillespie, G. Janossy, M. C. I. Lipman

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Background: Immunological ex vivo assays to diagnose tuberculosis (TB) have great potential but have largely been blood-based and poorly evaluated in active TB. Lung sampling enables combined microbiological and immunological testing and uses higher frequency antigen-specific responses than in blood.

Methods: A prospective evaluation was undertaken of a flow cytometric assay measuring the percentage of interferon-gamma synthetic CD4+ lymphocytes following stimulation with purified protein derivative of Mycobacterium tuberculosis (PPD) in bronchoalveolar lavage fluid from 250 sputum smear-negative individuals with possible TB. A positive assay was defined as >1.5%.

Results: Of those who underwent lavage and were diagnosed with active TB, 95% (106/111) had a positive immunoassay (95% CI 89% to 98%). In 139 individuals deemed not to have active TB, 105 (76%) were immunoassay negative (95% CI 68% to 82%). Of the remaining 24% (34 cases) with a positive immunoassay, a substantial proportion had evidence of untreated TB; in two of these active TB was subsequently diagnosed. Assay performance was unaffected by HIV status, disease site or BCG vaccination. In culture-positive pulmonary cases, response to PPD was more sensitive than nucleic acid amplification testing (94% vs 73%). The use of early secretory antigen target-6 (ESAT-6) responses in 71 subjects was no better than PPD, and 19% of those with culture-confirmed TB and a positive PPD immunoassay had no detectable response to ESAT-6.

Conclusions: These findings suggest that lung-orientated immunological investigation is a potentially powerful tool in diagnosing individuals with sputum smear-negative active TB, regardless of HIV serostatus.

Original languageEnglish
Pages (from-to)67-71
Number of pages5
JournalThorax
Volume63
Issue number1
DOIs
Publication statusPublished - Jan 2008

Keywords

  • MYCOBACTERIUM-TUBERCULOSIS
  • PULMONARY TUBERCULOSIS
  • DIAGNOSIS
  • RESPONSES
  • AMPLIFICATION
  • ANTIGENS

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