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A T-cell-based enzyme-linked immunospot assay for tuberculosis screening in Chinese patients with rheumatic diseases receiving infliximab therapy

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Abstract

Anti-tumour necrosis factor-α (TNF-α) therapy brought new hopes for treating rheumatic diseases but also increased the risk of infection, including mycobacterium tuberculosis (MTb). Conventional screening tools, such as tuberculin skin test (TST), lack sensitivity or specificity. Recently, T-SPOT.TB has been introduced to detect tuberculosis infection. Reports have proved its superior performance in detecting tuberculosis infection in various patient populations than the TST. To compare the value of a T-cell-based enzyme-linked immunospot assay (ELISPOT) T-SPOT.TB and conventional (TST) in screening and monitoring tuberculosis in patients with rheumatic diseases during infliximab therapy in China. Fifty-eight patients with various rheumatic diseases who received infliximab therapy were enrolled in the trial. Freshly isolated peripheral blood mononuclear cells were stimulated with MTb-specific antigens (ESAT-6 and CFP10), and IFN-γ-producing cells were counted. TST was performed with 1 TU PPD injected intradermally into the volar aspect of forearm. A cutaneous induration with diameter ≥5 mm was considered as positive TST, and an increment ≥5 mm of cutaneous induration was considered as TST conversion. TST and T-SPOT.TB test were carried out at baseline and repeated 12 months after infliximab therapy (if no active TB occurs) or at times when TB occurred. Moreover, all patients were initially evaluated for latent tuberculosis infection (LTBI) with clinical examination and chest radiograph. The McNemar test was used for TST and T-SPOT.TB concordance analysis. Cohen’s kappa coefficient was used to assess strength of the agreement. Among the 58 patients evaluated, 25 (43.1%) had ankylosing spondylitis, 24 (41.4%) had rheumatoid arthritis, 4 (6.9%) had undifferentiated spondyloarthropathy, 3 (5.2%) had psoriatic arthritis and 2 (3.4%) had reactive arthritis. A total of 52 patients (89.7%) had previously received vaccination with Bacille Calmette-Guerin. All of the patients received either single or combination of disease modifying anti-rheumatic drug (DMARDs) therapy, and 16 (27.4%) had previously or presently received glucocorticoid therapy. Before infliximab therapy, 12 patients (20.7%) had positive and 46 (79.3%) had negative TST results, and only 1 (1.7%) had positive T-SPOT.TB. Among 51 patients completing the repeated TST and T-SPOT.TB assay, 7 patients (13.7%) had TST conversion and 4 (7.8%) had positive T-SPOT.TB results. Of 7 patients with TST conversion, 2 patients (28.6%) developed active TB and also had positive T-SPOT.TB results; of 44 patients with no TST conversion, 2 patients (4.5%) had positive T-SPOT.TB and 1 (2.3%) had active TB. If 5 mm was used as the cut-off value of TST, TST and T-SPOT.TB, had an agreement value of 68.6% with a kappa value of 0.166. If 10 mm was used as the cut-off value, the agreement between TST and T-SPOT.TB was 88.2% with a kappa value of 0.338. T-SPOT.TB was more specific than TST in detecting tuberculosis during infliximab therapy in China with high BCG vaccination and high prevalence of TB. It can be used as a reliable tool for TB monitoring during infliximab therapy in Chinese patients with rheumatic diseases. Finally, it is recommended to repeat the TST and T-SPOT.TB periodically during biological treatment.

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References

  1. van der Kooij SM, le Cessie S, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, van Zeben D, Kerstens PJ et al (2009) Clinical and radiological efficacy of initial vs delayed treatment with infliximab plus methotrexate in patients with early rheumatoid arthritis. Ann Rheum Dis 68(7):1153–1158

    Article  PubMed  Google Scholar 

  2. Montecucco C (2005) In early rheumatoid arthritis the combination of methotrexate and infliximab over 2 years reduces the progression of radiological lesions more than methotrexate alone. Clin Exp Rheumatol 23(3):289–291

    PubMed  Google Scholar 

  3. Roach DR, Bean AG, Demangel C, France MP, Briscoe H, Britton WJ (2002) TNF regulates chemokine induction essential for cell recruitment, granuloma formation, and clearance of mycobacterial infection. J Immunol 168(9):4620–4627

    PubMed  CAS  Google Scholar 

  4. Jacobs M, Marino MW, Brown N, Abel B, Bekker LG, Quesniaux VJ et al (2000) Correction of defective host response to Mycobacterium bovis BCG infection in TNF-deficient mice by bone marrow transplantation. Lab Invest 80(6):901–914

    PubMed  CAS  Google Scholar 

  5. Miller EA, Ernst JD (2009) Anti-TNF immunotherapy and tuberculosis reactivation: another mechanism revealed. J Clin Invest 119(5):1079–1082

    Article  PubMed  CAS  Google Scholar 

  6. Bruns H, Meinken C, Schauenberg P, Harter G, Kern P, Modlin RL et al (2009) Anti-TNF immunotherapy reduces CD8 + T cell-mediated antimicrobial activity against Mycobacterium tuberculosis in humans. J Clin Invest 119(5):1167–1177

    Article  PubMed  CAS  Google Scholar 

  7. Wallis RS (2007) Reactivation of latent tuberculosis by TNF blockade: the role of interferon gamma. J Investig Dermatol Symp Proc 12(1):16–21

    Article  PubMed  CAS  Google Scholar 

  8. Tuberculosis NTSGotESSf (2002) Report on fourth national epidemiological sampling survey of tuberculosis. Chin J Tuberc Respir Dis 25(1):4

    Google Scholar 

  9. Mori T, Sakatani M, Yamagishi F, Takashima T, Kawabe Y, Nagao K et al (2004) Specific detection of tuberculosis infection: an interferon-gamma-based assay using new antigens. Am J Respir Crit Care Med 170(1):59–64

    Article  PubMed  Google Scholar 

  10. Meier T, Eulenbruch HP, Wrighton-Smith P, Enders G, Regnath T (2005) Sensitivity of a new commercial enzyme-linked immunospot assay (T SPOT-TB) for diagnosis of tuberculosis in clinical practice. Eur J Clin Microbiol Infect Dis 24(8):529–536

    Article  PubMed  CAS  Google Scholar 

  11. Jiang W, Shao L, Zhang Y, Zhang S, Meng C, Xu Y et al (2009) High-sensitive and rapid detection of Mycobacterium tuberculosis infection by IFN-gamma release assay among HIV-infected individuals in BCG-vaccinated area. BMC Immunol 10:31

    Google Scholar 

  12. Chapman AL, Munkanta M, Wilkinson KA, Pathan AA, Ewer K, Ayles H et al (2002) Rapid detection of active and latent tuberculosis infection in HIV-positive individuals by enumeration of Mycobacterium tuberculosis-specific T cells. AIDS 16(17):2285–2293

    Article  PubMed  Google Scholar 

  13. Kaymakcalan Z, Sakorafas P, Bose S, Scesney S, Xiong L, Hanzatian DK et al (2009) Comparisons of affinities, avidities, and complement activation of adalimumab, infliximab, and etanercept in binding to soluble and membrane tumor necrosis factor. Clin Immunol 131(2):308–316

    Article  PubMed  CAS  Google Scholar 

  14. Scallon B, Cai A, Solowski N, Rosenberg A, Song XY, Shealy D et al (2002) Binding and functional comparisons of two types of tumor necrosis factor antagonists. J Pharmacol Exp Ther 301(2):418–426

    Article  PubMed  CAS  Google Scholar 

  15. Gardam MA, Keystone EC, Menzies R, Manners S, Skamene E, Long R et al (2003) Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet Infect Dis 3(3):148–155

    Article  PubMed  CAS  Google Scholar 

  16. Mohan VP, Scanga CA, Yu K, Scott HM, Tanaka KE, Tsang E et al (2001) Effects of tumor necrosis factor alpha on host immune response in chronic persistent tuberculosis: possible role for limiting pathology. Infect Immun 69(3):1847–1855

    Article  PubMed  CAS  Google Scholar 

  17. Carmona L, Hernandez-Garcia C, Vadillo C, Pato E, Balsa A, Gonzalez-Alvaro I et al (2003) Increased risk of tuberculosis in patients with rheumatoid arthritis. J Rheumatol 30(7):1436–1439

    PubMed  Google Scholar 

  18. Bouza E, Moya JG, Munoz P (2001) Infections in systemic lupus erythematosus and rheumatoid arthritis. Infect Dis Clin North Am 15(2):335–361, vii

    Google Scholar 

  19. Binymin K, Cooper RG (2001) Late reactivation of spinal tuberculosis by low-dose methotrexate therapy in a patient with rheumatoid arthritis. Rheumatology (Oxford) 40(3):341–342

    Article  CAS  Google Scholar 

  20. Takasaka N, Toyota E, Shimada M, Ariga H, Teramoto S, Akagawa S (2010) Two cases of tuberculosis after treatment of rheumatoid arthritis with infliximab. Nihon Kokyuki Gakkai Zasshi 48(1):60–65

    PubMed  Google Scholar 

  21. Fortaleza GT, Brito Mde F, Santos JB, Figueiredo AR, Gomes P (2009) Splenic tuberculosis during psoriasis treatment with infliximab. An Bras Dermatol 84(4):420–424

    Article  PubMed  Google Scholar 

  22. Vieira WP, Nobre CA, Filho JD, Vieira RM, Callado MR (2009) Tuberculosis meningitis during infliximab therapy. Acta Reumatol Port 34(4):681–682

    PubMed  Google Scholar 

  23. Winthrop KL, Siegel JN (2004) Tuberculosis cases associated with infliximab and etanercept. Clin Infect Dis 39(8):1256–1257

    Article  PubMed  Google Scholar 

  24. Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD et al (2001) Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 345(15):1098–1104

    Article  PubMed  CAS  Google Scholar 

  25. Saag KG, Teng GG, Patkar NM, Anuntiyo J, Finney C, Curtis JR et al (2008) American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 59(6):762–784

    Article  PubMed  CAS  Google Scholar 

  26. Chadha VK, Jagannath PS, Nagaraj AV, Narayana Prasad D, Anantha N (2000) A comparative study of tuberculin reactions to 1 TU and 2 TU of PPD- RT23. Indian J TB 47:15–20

    Google Scholar 

  27. Hoskyns EW, Simpson H, Monk P (1994) Use of the 1 tuberculin unit (TU) Mantoux test in the assessment of tuberculous infection in children following neonatal BCG vaccination. Thorax 49(10):1006–1009

    Article  PubMed  CAS  Google Scholar 

  28. Chen DY, Shen GH, Hsieh TY, Hsieh CW, Lan JL (2008) Effectiveness of the combination of a whole-blood interferon-gamma assay and the tuberculin skin test in detecting latent tuberculosis infection in rheumatoid arthritis patients receiving adalimumab therapy. Arthritis Rheum 59(6):800–806

    Article  PubMed  CAS  Google Scholar 

  29. Kim HA, Yoo CD, Baek HJ, Lee EB, Ahn C, Han JS et al (1998) Mycobacterium tuberculosis infection in a corticosteroid-treated rheumatic disease patient population. Clin Exp Rheumatol 16(1):9–13

    PubMed  CAS  Google Scholar 

  30. Targeted tuberculin testing and treatment of latent tuberculosis infection (2000) American Thoracic Society. MMWR Recomm Rep 49(RR-6):1–51

  31. Teixeira EG, Kritski A, Ruffino-Netto A, Steffen R, Lapa ESJR, Belo M et al (2008) Two-step tuberculin skin test and booster phenomenon prevalence among Brazilian medical students. Int J Tuberc Lung Dis 12(12):1407–1413

    PubMed  CAS  Google Scholar 

  32. Jeon K, Ji SH, Oh SY, Lee JB, Kim HJ, Choi CM (2008) Boosted reaction on two-step tuberculin skin test among military personnel in South Korea, a setting with an intermediate burden of tuberculosis and routine bacille Calmette-Guerin vaccination. J Korean Med Sci 23(3):402–405

    Article  PubMed  Google Scholar 

  33. Laffitte E, Janssens JP, Roux-Lombard P, Thielen AM, Barde C, Marazza G et al (2009) Tuberculosis screening in patients with psoriasis before antitumour necrosis factor therapy: comparison of an interferon-gamma release assay vs. tuberculin skin test. Br J Dermatol 161(4):797–800

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Rheumatology, The Second Xiangya Hospital, Central South University, Changsha, HU-NAN, 410011, China

    Xi Xie, Jin-wei Chen, Fen Li, Jing Tian & Jie-sheng Gao

  2. Department of Bioengineering, University of Washington, Seattle, WA, 98195, USA

    David Zhang

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  1. Xi Xie
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Correspondence to Jin-wei Chen.

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Xie, X., Chen, Jw., Li, F. et al. A T-cell-based enzyme-linked immunospot assay for tuberculosis screening in Chinese patients with rheumatic diseases receiving infliximab therapy. Clin Exp Med 11, 155–161 (2011). https://doi.org/10.1007/s10238-010-0123-4

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