Evaluation of latent tuberculosis infection in patients with inflammatory arthropathies before treatment with TNF-? blocking drugs using a novel flow-cytometric interferon-? release assay

Objective: To compare the efficacy of the conventional skin test and a novel flow cytometric whole blood assay in the diagnosis of latent tuberculosis infection (LTBI) in patients with rheumatologic diseases evaluated for treatment with tumour necrosis factor (TNF)-α-blocking agents. Methods: Prospective study of 97 consecutively enrolled patients, who were assessed for the presence of LTBI through clinical history, Mendel-Mantoux skin testing, and chest x-ray. In addition, T-cell reactivity towards tuberculin (PPD) and the M. tuberculosis specific proteins ESAT-6 and CFP-10 was determined ex vivo using a flow cytometric whole blood assay. Results: After standard screening, 15% of patients receiving TNF-α-blocking therapy were pretreated with isoniazide (INH), another 5% of patients did not receive TNF-α-blocking therapy because of LTBI. PPD-reactivity in the skin was observed in 14% of patients compared to 39% with the whole blood test. Analysis of the M. tuberculosis specific response to ESAT-6 and CFP-10 revealed positive results in 16% of patients. Using a decision tree incorporating history, chest x-ray and either skin-test or ESAT-6/CFP-10 results, 18 or 22% of patients, respectively, were classified as latently infected with M. tuberculosis. Four patients treated with INH because of a positive skin reaction did not show reactivity to ESAT-6/CFP-10 in the whole blood assays. Another six patients not pretreated with INH because of negative skin tests would have received INH, had the results of the whole blood assay been taken into account. Conclusion: The Mendel-Mantoux skin test has a low sensitivity and specificity for the diagnosis of LTBI in this cohort of patients, potentially resulting in both overand undertreatment with prophylactic INH when compared to the flow cytometric analysis of whole blood T-cell reactivity to proteins specific to M. tuberculosis. Use of T-cell based in vitro tests may help to refine diagnostic testing for LTBI.