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Detection of latent tuberculosis in immunosuppressed patients with autoimmune diseases: performance of a Mycobacterium tuberculosis antigen-specific interferon assay

¹ Department of Rheumatology and Clinical Immunology/Allergology, University of Bern, Switzerland
² Division of Clinical Epidemiology and Biostatistics, Department of Social and Preventive Medicine, University of Bern, Switzerland

Correspondence to:
Professor S Gadola, Division of Infection, Inflammation and Repair, University of Southampton, Tremona Road, Southampton SO16 6YD, UK, s.gadola{at}soton.ac.uk

Objective: To analyse the performance of a new M tuberculosis-specific interferon (IFN) assay in patients with chronic inflammatory diseases who receive immunosuppressive drugs, including tumour necrosis factor (TNF) inhibitors.

Methods: Cellular immune responses to the M tuberculosis-specific antigens ESAT-6, CFP-10, TB7.7 were prospectively studied in 142 consecutive patients treated for inflammatory rheumatic conditions. Results were compared with tuberculin skin tests (TSTs). Association of both tests with risk factors for latent M tuberculosis infection (LTBI) and BCG vaccination were determined and the influence of TNF inhibitors, corticosteroids, and disease modifying antirheumatic drugs (DMARDs) on antigen-specific and mitogen-induced IFN secretion was analysed.

Results: 126/142 (89%) patients received immunosuppressive therapy. The IFN assay was more closely associated with the presence of risk factors (odds ratio (OR) = 23.8 (95% CI 5.14 to 110) vs OR = 2.77 (1.22 to 6.27), respectively; p = 0.009), but less associated with BCG vaccination than the TST (OR = 0.47 (95% CI 0.15 to 1.47) vs OR = 2.44 (0.74 to (8.01), respectively; p = 0.025). Agreement between the IFN assay and TST results was low ( = 0.17; 95% CI 0.02 to 0.32). The odds for a positive IFN assay strongly increased with increasing prognostic relevance of LTBI risk factors. Neither corticosteroids nor conventional DMARDs significantly affected IFN responses, but the odds for a positive IFN assay were decreased in patients treated with TNF inhibitors (OR = 0.21 (95% CI 0.07 to 0.63), respectively; p = 0.006).

Conclusions: These results demonstrate that the performance of the M tuberculosis antigen-specific IFN ELISA is better than the classic TST for detection of LTBI in patients receiving immunosuppressive therapy for treatment of systemic autoimmune disorders.

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