Diagnosis of Active Tuberculous Serositis by Antigen-Specific Interferon- Response of Cavity Fluid Cells

Jan 15, 2008Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

Diagnosing active tuberculous fluid inflammation using immune response in cavity fluid cells

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Abstract

Cavity fluid IFN-gamma responses were significantly higher in active tuberculous serositis patients compared to those with nontuberculous effusions.

The area under the receiver operating characteristic (AUROC) curve for cavity fluid IFN-gamma response was 0.996, indicating high diagnostic accuracy.
Cavity fluid IFN-gamma response outperformed both cavity fluid adenosine deaminase (AUROC 0.882) and whole-blood IFN-gamma responses (AUROC 0.719).
The difference in AUROC curves between cavity fluid IFN-gamma response and background cavity fluid IFN-gamma level was not statistically significant (P = .74).
Multivariate logistic regression analysis indicated that cavity fluid IFN-gamma responses were significantly associated with the diagnosis of active tuberculous serositis, even after adjusting for background levels.

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BACKGROUND: To develop a more accurate methodology for diagnosing active tuberculous pleurisy, as well as peritonitis and pericardits of tuberculous origin, we established an antigen-specific interferon gamma (IFN-gamma)-based assay that uses cavity fluid specimens.

METHODS: Over a 19-month period, 155 consecutive, nonselected patients with any cavity effusion were evaluated. Study subjects were 28 patients with bacteriologically confirmed active tuberculous serositis and 47 patients with definitive nontuberculous etiology. Culture was performed for 18 h with fluid mononuclear cells in the supernatant of the effusion together with saline or Mycobacterium tuberculosis-specific antigenic peptides, early secretory antigenic target 6 and culture filtrate protein 10. IFN-gamma concentrations in the culture supernatants were measured.

RESULTS: In patients with active tuberculous serositis, antigen-specific IFN-gamma responses of cavity fluid samples were significantly higher than those of nontuberculous effusion samples. Area under the receiver operating characteristic (AUROC) curve was significantly greater for cavity fluid IFN-gamma response (AUROC curve, 0.996) than for cavity fluid adenosine deaminase and whole-blood IFN-gamma responses (AUROC curve, 0.882 and 0.719, respectively; P = .037 and P < .001, respectively). Although the AUROC curve was greater for cavity fluid IFN-gamma response than for background cavity fluid IFN-gamma level (AUROC curve, 0.975), the AUROC curves were not statistically significantly different (P = .74). However, multivariate logistic regression analysis revealed that cavity fluid IFN-gamma responses were significantly associated with the diagnosis, even after adjustment for background IFN-gamma level (adjusted odds ratio, 1.21; 95% confidence interval, 1.03-1.42; P < .001).

CONCLUSIONS: The cavity fluid IFN-gamma assay could be a method for accurately and promptly diagnosing active tuberculous serositis.

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