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Clinical Rheumatology

, Volume 31, Issue 11, pp 1567–1575 | Cite as

Serial interferon-γ release assays for screening and monitoring of tuberculosis infection during treatment with biologic agents

  • Rossana Scrivo
  • Ilaria Sauzullo
  • Fabio Mengoni
  • Giancarlo Iaiani
  • Anna Rita Vestri
  • Roberta Priori
  • Elisa Di Filippo
  • Manuela Di Franco
  • Francesca Romana Spinelli
  • Vincenzo Vullo
  • Claudio Maria Mastroianni
  • Guido Valesini
Original Article

Abstract

Screening for latent tuberculosis infection (LTBI) prior to the prescribing of anti-TNF agents and monitoring for infection during treatment are recommended. The feasibility of novel screening tools, including QuantiFERON-TB Gold In-Tube (QFT-GIT), remains unclear in the setting of immunosuppression. The aim of this study was to evaluate the usefulness of serial QFT-GIT during biologic therapy to assess whether dynamic changes in IFN-γ levels may be helpful in identifying reactivation of LTBI or newly acquired TB. We conducted a prospective study on patient candidates to TNF inhibitors. QFT-GIT was performed at baseline and after 3 and 6 months since biologic onset. A further follow-up period of 6 months was observed. Among patients enrolled (n = 119; F = 69 %; median age = 47 years, range 18–80), 24 had at least 1 risk factor for LTBI. Ninety-six were taking immunosuppressants at the time of TB testing. At baseline, 5 patients displayed positive, 93 negative, and 21 indeterminate QFT-GIT results. We observed QFT-GIT conversions and reversions in 12 patients with LTBI and in 73 without LTBI. QFT-GIT results changed of 28 % at month 3 and of 21 % at month 6; the greatest change was observed in patients with indeterminate results that became negative (15 %; p < 0.02). No TB cases were detected. In conclusion, the routine use of both QFT-GIT and TST at screening seems not to give any advantage in the setting of patients awaiting biologics. In addition, the feasibility of serial QFT-GIT during biologic therapy needs definition since changes in IFN-γ levels may occur without a pathologic connotation.

Keywords

Anti-TNF QuantiFERON-TB Gold In-Tube Rheumatoid arthritis Tuberculin skin test 

Notes

Disclosures

None.

References

  1. 1.
    Furst DE, Keystone EC, Braun J, Breedveld FC, Burmester GR, De Benedetti F, Dörner T, Emery P, Fleischmann R, Gibofsky A, Kalden JR, Kavanaugh A, Kirkham B, Mease P, Sieper J, Singer NG, Smolen JS, Van Riel PL, Weisman MH, Winthrop K (2012) Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2011. Ann Rheum Dis 71(Suppl 2):i2–i45PubMedCrossRefGoogle Scholar
  2. 2.
    Gardam MA, Keystone EC, Menzies R, Manners S, Skamene E, Long R, Vinh DC (2003) Anti-tumor necrosis factor agents and tuberculosis risk: mechanism of action and clinical management. Lancet Infect Dis 3(3):148–155PubMedCrossRefGoogle Scholar
  3. 3.
    Dixon WG, Hyrich KL, Watson KD, Lunt M, Galloway J, Ustianowski A, BSRBR Control Centre Consortium, Symmons DP; BSR Biologics Register (2010) Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR). Ann Rheum Dis 69(3):522–528PubMedCrossRefGoogle Scholar
  4. 4.
    Tubach F, Salmon D, Ravaud P, Allanore Y, Goupille P, Bréban M, Pallot-Prades B, Pouplin S, Sacchi A, Chichemanian RM, Bretagne S, Emilie D, Lemann M, Lortholary O, Mariette X, Research Axed on Tolerance of Biotherapies Group (2009) Risk of tuberculosis is higher with antitumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: the three-year prospective French Research Axed on Tolerance of Biotherapies registry. Arthritis Rheum 60(7):1884–1894PubMedCrossRefGoogle Scholar
  5. 5.
    Wallis RS (2008) Tumour necrosis factor antagonists: structure, function, and tuberculosis risks. Lancet Infect Dis 8(10):601–611PubMedCrossRefGoogle Scholar
  6. 6.
    Targeted tuberculin testing and treatment of latent tuberculosis infection. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. This is a Joint Statement of the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC). This statement was endorsed by the Council of the Infectious Diseases Society of America. (IDSA), September 1999, and the sections of this statement (2000) Am J Respir Crit Care Med 161(4 Pt 2):S221–S247Google Scholar
  7. 7.
    Pai M, Menzies D (2007) The new IGRA and the old TST. Making good use of disagreement. Am J Respir Crit Care Med 175(6):529–531PubMedCrossRefGoogle Scholar
  8. 8.
    Mazurek GH, Jereb J, Vernon A, LoBue P, Goldberg S, Castro K, IGRA Expert Committee; Centers for Disease Control and Prevention (CDC) (2010) Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection—United States, 2010. MMWR Recomm Rep 59(RR-5):1–25PubMedGoogle Scholar
  9. 9.
    Menzies D (1999) Interpretation of repeated tuberculin tests. Boosting, conversion, and reversion. Am J Respir Crit Care Med 159(1):15–21PubMedGoogle Scholar
  10. 10.
    Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3):315–324PubMedCrossRefGoogle Scholar
  11. 11.
    Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H, Study Group CASPAR (2006) Classification criteria for psoriatic arthritis. Development of new criteria from a large international study. Arthritis Rheum 54(8):2665–2673PubMedCrossRefGoogle Scholar
  12. 12.
    van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis: a proposal for modification of the New York criteria. Arthritis Rheum 27(4):361–368PubMedCrossRefGoogle Scholar
  13. 13.
    International Study Group for Behcet’s Disease: Criteria for diagnosis of Behcet’s disease (1990) Lancet 335(8697):1078–1080Google Scholar
  14. 14.
    Brock I, Ruhwald M, Lundgren B, Westh H, Mathiesen LR, Ravn P (2006) Latent tuberculosis in HIV positive, diagnosed by the M. tuberculosis specific interferon-gamma test. Respir Res 7:56PubMedCrossRefGoogle Scholar
  15. 15.
    Ferrara G, Losi M, D’Amico R, Roversi P, Piro R, Meacci M, Meccugni B, Dori IM, Andreani A, Bergamini BM, Mussini C, Rumpianesi F, Fabbri LM, Richeldi L (2006) Use in routine clinical practice of two commercial blood tests for diagnosis of infection with Mycobacterium tuberculosis: a prospective study. Lancet 367(9519):1328–1334PubMedCrossRefGoogle Scholar
  16. 16.
    Bocchino M, Matarese A, Bellofiore B, Giacomelli P, Santoro G, Balato N, Castiglione F, Scarpa R, Perna F, Signoriello G, Galati D, Ponticiello A, Sanduzzi A (2008) Performance of two commercial blood IFN-gamma release assays for the detection of Mycobacterium tuberculosis infection in patient candidates for anti-TNF-alpha treatment. Eur J Clin Microbiol Infect Dis 27(10):907–913PubMedCrossRefGoogle Scholar
  17. 17.
    Matulis G, Juni P, Villiger PM, Gadola SD (2008) Detection of latent tuberculosis in immunosuppressed patients with autoimmune diseases: performance of a Mycobacterium tuberculosis antigen-specific interferon gamma assay. Ann Rheum Dis 67(1):84–90PubMedCrossRefGoogle Scholar
  18. 18.
    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):800–806PubMedCrossRefGoogle Scholar
  19. 19.
    Ponce de Leon D, Acevedo-Vasquez E, Alvizuri S, Gutierrez C, Cucho M, Alfaro J, Perich R, Sanchez-Torres A, Pastor C, Sanchez-Schwartz C, Medina M, Gamboa R, Ugarte M (2008) Comparison of an interferon gamma assay with tuberculin skin testing for detection of tuberculosis (TB) infection in patients with rheumatoid arthritis in a TB-endemic population. J Rheumatol 35(5):776–781PubMedGoogle Scholar
  20. 20.
    Sauzullo I, Mengoni F, Scrivo R, Valesini G, Potenza C, Skroza N, Marocco R, Lichtner M, Vullo V, Mastroianni CM (2010) Evaluation of QuantiFERON-TB Gold In-Tube in human immunodeficiency virus infection and in patient candidates for anti-tumor necrosis factor-alpha treatment. Int J Tuberc Lung Dis 14(7):834–840PubMedGoogle Scholar
  21. 21.
    Martin J, Walsh C, Gibbs A, McDonnell T, Fearon U, Keane J, Codd MB, Dodd J, Veale D, Fitzgerald O, Bresnihan B (2010) Comparison of interferon gamma release assays and conventional screening tests before tumour necrosis factor alpha blockade in patients with inflammatory arthritis. Ann Rheum Dis 69(1):181–185PubMedCrossRefGoogle Scholar
  22. 22.
    Ferrara G, Losi M, Meacci M, Meccugni B, Piro R, Roversi P, Bergamini BM, D’Amico R, Marchegiano P, Rumpianesi F, Fabbri LM, Richeldi L (2005) Routine hospital use of a new commercial whole blood interferon-gamma assay for the diagnosis of tuberculosis infection. Am J Respir Crit Care Med 172(5):631–635PubMedCrossRefGoogle Scholar
  23. 23.
    Solovic I, Sester M, Gomez-Reino JJ, Rieder HL, Ehlers S, Milburn HJ, Kampmann B, Hellmich B, Groves R, Schreiber S, Wallis RS, Sotgiu G, Schölvinck EH, Goletti D, Zellweger JP, Diel R, Carmona L, Bartalesi F, Ravn P, Bossink A, Duarte R, Erkens C, Clark J, Migliori GB, Lange C (2010) The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement. Eur Respir J 36(5):1185–1206PubMedCrossRefGoogle Scholar
  24. 24.
    Chen DY, Shen GH, Chen YM, Chen HH, Hsieh CW, Lan JL (2012) Biphasic emergence of active tuberculosis in rheumatoid arthritis patients receiving TNF{alpha} inhibitors: the utility of IFN{gamma} assay. Ann Rheum Dis 71(2):231–237PubMedCrossRefGoogle Scholar
  25. 25.
    Kleinert S, Kurzai O, Elias J, Marten K, Engelke C, Feuchtenberger M, Sandstede J, Frosch M, Tony HP, Kneitz C (2010) Comparison of two interferon-gamma release assays and tuberculin skin test for detecting latent tuberculosis in patients with immune-mediated inflammatory diseases. Ann Rheum Dis 69(4):782–784PubMedCrossRefGoogle Scholar
  26. 26.
    Bélard E, Semb S, Ruhwald M, Werlinrud AM, Soborg B, Jensen FK, Thomsen H, Brylov A, Hetland ML, Nordgaard-Lassen I, Ravn P (2011) Prednisolone treatment affects the performance of the QuantiFERON gold in-tube test and the tuberculin skin test in patients with autoimmune disorders screened for latent tuberculosis infection. Inflamm Bowel Dis 17(11):2340–2349PubMedCrossRefGoogle Scholar
  27. 27.
    Vassilopoulos D, Stamoulis N, Hadziyannis E, Archimandritis AJ (2008) Usefulness of enzyme-linked immunospot assay (Elispot) compared to tuberculin skin testing for latent tuberculosis screening in rheumatic patients scheduled for anti-tumor necrosis factor treatment. J Rheumatol 35(7):1271–1276PubMedGoogle Scholar
  28. 28.
    Leyten EM, Arend SM, Prins C, Cobelens FG, Ottenhoff TH, van Dissel JT (2007) Discrepancy between mycobacterium tuberculosis-specific gamma interferon release assays using short and prolonged in vitro incubation. Clin Vaccine Immunol 14(7):880–885PubMedCrossRefGoogle Scholar
  29. 29.
    Kwakernaak AJ, Houtman PM, Weel JF, Spoorenberg JP, Jansen TL (2011) A comparison of an interferon-gamma release assay and tuberculin skin test in refractory inflammatory disease patients screened for latent tuberculosis prior to the initiation of a first tumor necrosis factor α inhibitor. Clin Rheumatol 30(4):505–510PubMedCrossRefGoogle Scholar
  30. 30.
    Gomez-Reino JJ, Carmano L, Descalzo A, BIOBADASER GROUP (2007) Risk of tuberculosis in patients treated with tumor necrosis factor antagonists due to incomplete prevention of reactivation of latent infection. Arthritis Rheum 57(5):756–761PubMedCrossRefGoogle Scholar
  31. 31.
    Park JH, Seo GY, Lee JS, Kim TH, Yoo DH (2009) Positive conversion of tuberculin skin test and performance of interferon release assay to detect hidden tuberculosis infection during antitumor necrosis factor agent trial. J Rheumatol 36(10):2158–2163PubMedCrossRefGoogle Scholar
  32. 32.
    Takahashi H, Shigehara K, Yamamoto M, Suzuki C, Naishiro Y, Tamura Y, Hirohashi Y, Satoh N, Shijubo N, Shinomura Y, Imai K (2007) Interferon γ assay for detecting latent tuberculosis infection in rheumatoid arthritis patients during infliximab administration. Rheumatol Int 27(12):1143–1148PubMedCrossRefGoogle Scholar
  33. 33.
    Garcovich S, Ruggeri A, D’Agostino M, Ardito F, De Simone C, Delogu G, Fadda G (2012) Clinical applicability of Quantiferon-TB-Gold testing in psoriasis patients during long-term anti-TNF-alpha treatment: a prospective, observational study. J Eur Acad Dermatol Venereol. doi: 10.1111/j.1468-3083.2011.04220.xGoogle Scholar
  34. 34.
    Kim KH, Lee SW, Chung WT, Kim BG, Woo KS, Han JY, Kim JM (2011) Serial interferon-gamma release assays for the diagnosis of latent tuberculosis infection in patients treated with immunosuppressive agents. Korean J Lab Med 31(4):271–278PubMedCrossRefGoogle Scholar
  35. 35.
    Ringrose JS, Sanche SE, Taylor-Gjevre RM (2011) Detecting latent tuberculosis infection during antitumor necrosis factor therapy. Clin Exp Rheumatol 29(5):790–794PubMedGoogle Scholar
  36. 36.
    Carrara S, Vincenti D, Petrosillo N, Amicosante M, Girardi E, Goletti D (2004) Use of a T cell-based assay for monitoring efficacy of antituberculosis therapy. Clin Infect Dis 38(5):754–756PubMedCrossRefGoogle Scholar
  37. 37.
    Katiyar SK, Sampath A, Bihari S, Mamtani M, Kulkarni H (2008) Use of the QuantiFERON-TB Gold In-Tube test to monitor treatment efficacy in active pulmonary tuberculosis. Int J Tuberc Lung Dis 12(10):1146–1152PubMedGoogle Scholar
  38. 38.
    Sauzullo I, Mengoni F, Lichtner M, Massetti AP, Rossi R, Iannetta M, Marocco R, Del Borgo C, Soscia F, Vullo V, Mastroianni CM (2009) In vivo and in vitro effects of antituberculosis treatment on mycobacterial interferon-gamma T cell response. PLoS One 4:e5187PubMedCrossRefGoogle Scholar
  39. 39.
    Veerapathran A, Joshi R, Goswami K, Dogra S, Moodie EE, Reddy MV, Kalantri S, Schwartzman K, Behr MA, Menzies D, Pai M (2008) T-cell assays for tuberculosis infection: deriving cut-offs for conversions using reproducibility data. PLoS One 3:e1850PubMedCrossRefGoogle Scholar
  40. 40.
    Herrera V, Yeh E, Murphy K, Parsonnet J, Banaei N (2010) Immediate incubation reduces indeterminate results for QuantiFERON-TB Gold in-tube assay. J Clin Microbiol 48(8):2672–2676PubMedCrossRefGoogle Scholar
  41. 41.
    Hamdi H, Mariette X, Godot V, Weldingh K, Hamid AM, Prejean MV, Baron G, Lemann M, Puechal X, Breban M, Berenbaum F, Delchier JC, Flipo RM, Dautzenberg B, Salmon D, Humbert M, Emilie D, RATIO (Recherche sur Anti-TNF et Infections Opportunistes) Study Group, (2006) Inhibition of anti-tuberculosis T-lymphocyte function with tumour necrosis factor antagonists. Arthritis Res Ther 8:R114PubMedCrossRefGoogle Scholar
  42. 42.
    Leyten EM, Prins C, Bossink AW, Thijsen S, Ottenhoff TH, van Dissel JT, Arend SM (2007) Effect of tuberculin skin testing on a Mycobacterium tuberculosis-specific interferon-gamma assay. Eur Respir J 29(6):1212–1216PubMedCrossRefGoogle Scholar
  43. 43.
    Richeldi L, Bergamini BM, Vaienti F (2008) Prior tuberculin skin testing does not boost QuantiFERON-TB results in paediatric contacts. Eur Respir J 32(2):524–525PubMedCrossRefGoogle Scholar
  44. 44.
    Sauzullo I, Massetti AP, Mengoni F, Rossi R, Lichtner M, Ajassa C, Vullo V, Mastroianni CM (2011) Influence of previous tuberculin skin test on serial IFN-γ release assays. Tuberculosis 91(4):322–326PubMedCrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2012

Authors and Affiliations

  • Rossana Scrivo
    • 1
  • Ilaria Sauzullo
    • 2
  • Fabio Mengoni
    • 2
  • Giancarlo Iaiani
    • 2
  • Anna Rita Vestri
    • 2
  • Roberta Priori
    • 1
  • Elisa Di Filippo
    • 2
  • Manuela Di Franco
    • 1
  • Francesca Romana Spinelli
    • 1
  • Vincenzo Vullo
    • 2
  • Claudio Maria Mastroianni
    • 3
  • Guido Valesini
    • 1
  1. 1.Dipartimento di Medicina Interna e Specialità Mediche, ReumatologiaSapienza Università di RomaRomeItaly
  2. 2.Dipartimento di Sanità Pubblica e Malattie InfettiveSapienza Università di RomaRomeItaly
  3. 3.UOC Malattie Infettive, Fondazione Eleonora Lorillard Spencer CenciSapienza Università di Roma (Polo Pontino)LatinaItaly

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