The principle of these methods is based on the detection of IFN-γ produced by the effectors memory T cells upon in vitro stimulation with the TB-specific antigens, early secretory antigen (ESAT) 6 and culture filtrate protein (CFP) 10. IFN can be measured using either ELISpot-based assay, represented by T-SPOT®.TB (Immunotech, Abingdon, UK), or an enzyme-linked immunosorbent assay (ELISA), represented by QFT-G and QFT-in-tube (QFT-IT; Cellestis, Victoria, Australia) [74]. Although QFT-G demonstrates

high specificity for LTBI FK228 order (96–99%), its sensitivity is still questionable (70–78%) [75]. In one study, LTBI treatment was avoided in 20% of patients with positive TST results but negative IGRA results [76]. The use of both methods in parallel can enhance both sensitivity and specificity. Furthermore, routine periodic retesting during therapy could allow for the detection of possible conversions. However, serial TST testing is not strictly I-BET151 molecular weight recommended due to the boosting effect [60]. There is also evidence that the TST can boost subsequent IGRA results. The effect is evident after the first 3 days post-TST testing and potentially wanes after a few months [77]. Furthermore, the use of IGRAs during immunosuppressive treatment (including biologic therapy) is controversial, because the immunosuppression might decrease the production

of IFN and interfere with the results [74]. Another inconvenience for both TST and IGRAs is the lack of discrimination between latent and active TB [60]. Positive TST/IGRAs tests at baseline often remain positive despite a successful anti-TB treatment. In these cases careful Cediranib (AZD2171) monitoring for clinical signs and symptoms of active TB is recommended [78]. According to the Tuberculosis Network European Trials Group (TBNET) consensus, the chemoprophylactic regimens recommended for LTBI include 6 or 9 months with isoniazid, 3 months of rifampicin plus isoniazid, or 4 months of rifampicin [79]. Another regimen used in the USA includes

rifampicin and pyrazinamide for 2 months, although this regimen has been associated with a high number of side effects [80]. The diagnostic tools for active TB infection include clinical assessment, cultures for M. tuberculosis, staining for acid-fast bacilli, chest X-rays, and nucleic acid amplification assays [9]. Although culture is considered the reference standard, in clinical practice the diagnosis and treatment of TB are usually based on the presence of abnormal radiologic findings or clinical suspicion [20]. The recommendations for resuming biologic therapy in active TB patients are controversial. According to the American College of Rheumatology (ACR), anti-TNF therapy can be initiated or resumed after 1 month of chemoprophylaxis for LTBI and after completion of therapy for active disease [78]. The British Society for Rheumatology (BSR) accepts the continuation of biologic therapy during TB treatment if clinically indicated [81]. Hernandez et al.