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

2.50
HDL Handle:
http://hdl.handle.net/10033/22313
Title:
Evaluation of latent tuberculosis infection in patients with inflammatory arthropathies before treatment with TNF-alpha blocking drugs using a novel flow-cytometric interferon-gamma release assay.
Authors:
Dinser, R; Fousse, M; Sester, U; Albrecht, K; Singh, M; Köhler, H; Müller-Ladner, U; Sester, M
Abstract:
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 rheumatological diseases evaluated for treatment with TNF-alpha-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, purified protein derivative) and the Mycobacterium 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-alpha-blocking therapy were pretreated with isoniazide (INH), another 5% of patients did not receive TNF-alpha-blocking therapy because of LTBI. PPD-reactivity in the skin was observed in 14% of patients compared with 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 the 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 over- and under-treatment with prophylactic INH when compared with 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.
Affiliation:
Department of Internal Medicine and Rheumatology, Justus-Liebig University of Giessen, Kerckhoff Clinic, Benekestrasse 2-8, D-61231 Bad Nauheim, Germany. r.dinser@kerckhoff-klinik.de
Citation:
Evaluation of latent tuberculosis infection in patients with inflammatory arthropathies before treatment with TNF-alpha blocking drugs using a novel flow-cytometric interferon-gamma release assay. 2008, 47 (2):212-8 Rheumatology (Oxford)
Journal:
Rheumatology (Oxford, England)
Issue Date:
Feb-2008
URI:
http://hdl.handle.net/10033/22313
DOI:
10.1093/rheumatology/kem351
PubMed ID:
18208824
Type:
Article
Language:
en
ISSN:
1462-0332
Appears in Collections:
Publications of Dept. Genome Analysis (GNA)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorDinser, R-
dc.contributor.authorFousse, M-
dc.contributor.authorSester, U-
dc.contributor.authorAlbrecht, K-
dc.contributor.authorSingh, M-
dc.contributor.authorKöhler, H-
dc.contributor.authorMüller-Ladner, U-
dc.contributor.authorSester, M-
dc.date.accessioned2008-04-04T11:55:57Z-
dc.date.available2008-04-04T11:55:57Z-
dc.date.issued2008-02-
dc.identifier.citationEvaluation of latent tuberculosis infection in patients with inflammatory arthropathies before treatment with TNF-alpha blocking drugs using a novel flow-cytometric interferon-gamma release assay. 2008, 47 (2):212-8 Rheumatology (Oxford)en
dc.identifier.issn1462-0332-
dc.identifier.pmid18208824-
dc.identifier.doi10.1093/rheumatology/kem351-
dc.identifier.urihttp://hdl.handle.net/10033/22313-
dc.description.abstractOBJECTIVE: 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 rheumatological diseases evaluated for treatment with TNF-alpha-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, purified protein derivative) and the Mycobacterium 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-alpha-blocking therapy were pretreated with isoniazide (INH), another 5% of patients did not receive TNF-alpha-blocking therapy because of LTBI. PPD-reactivity in the skin was observed in 14% of patients compared with 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 the 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 over- and under-treatment with prophylactic INH when compared with 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.en
dc.language.isoenen
dc.subject.meshAgeden
dc.subject.meshAnti-Inflammatory Agentsen
dc.subject.meshArthritis, Psoriaticen
dc.subject.meshArthritis, Rheumatoiden
dc.subject.meshCD4-Positive T-Lymphocytesen
dc.subject.meshFemaleen
dc.subject.meshFlow Cytometryen
dc.subject.meshHumansen
dc.subject.meshInterferon Type IIen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshMycobacterium tuberculosisen
dc.subject.meshPrednisoloneen
dc.subject.meshReproducibility of Resultsen
dc.subject.meshRheumatic Diseasesen
dc.subject.meshSensitivity and Specificityen
dc.subject.meshSkin Testsen
dc.subject.meshSpondylitis, Ankylosingen
dc.subject.meshTuberculosisen
dc.titleEvaluation of latent tuberculosis infection in patients with inflammatory arthropathies before treatment with TNF-alpha blocking drugs using a novel flow-cytometric interferon-gamma release assay.en
dc.typeArticleen
dc.contributor.departmentDepartment of Internal Medicine and Rheumatology, Justus-Liebig University of Giessen, Kerckhoff Clinic, Benekestrasse 2-8, D-61231 Bad Nauheim, Germany. r.dinser@kerckhoff-klinik.deen
dc.identifier.journalRheumatology (Oxford, England)en

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