Lab Med Online.  2016 Jan;6(1):8-11. 10.3343/lmo.2016.6.1.8.

Clinical Applications of Interferon-gamma Release Assays

• Woo KS
• Kim KH

• KMID: 2312285
• DOI: http://doi.org/10.3343/lmo.2016.6.1.8

Abstract

Mycobacterium tuberculosis infection remains an important problem in Korea and globally. Interferon-gamma release assays (IGRAs) are blood-based tests that measure the amount of interferon-gamma released by T lymphocytes after stimulation by antigens specific for M. tuberculosis. IGRAs are not recommended for diagnosis of active pulmonary tuberculosis because they cannot distinguish between latent tuberculosis infection (LTBI) and the active disease. For extrapulmonary tuberculosis, IGRAs are considered adjuvant diagnostic tools. The diagnostic performance of IGRAs differs according to infection site. The sensitivity of IGRAs in children is suboptimal in low- and middle-income countries. In Korea, for children who have received a M. bovis bacille Calmette-Guerin (BCG) vaccine after 1 yr of age or have been inoculated with the BCG vaccine twice or more, IGRA is recommended instead of the tuberculin skin test (TST). Diagnosis and treatment of LTBI before the initiation of anti-tumor necrosis factor (TNF) agents are recommended in patients with immune-mediated inflammatory diseases because anti-TNF therapy is associated with an increased risk of developing tuberculosis. A strategy using both TST and IGRA is used for immunocompromised adults in Korea; positive results obtained by either test confirm a diagnosis of LTBI. Negative results of only TST are not considered conclusively negative for LTBI. In addition to interferon-gamma, a biomarker to discriminate between active and latent tuberculosis is required, and IP-10 and IL-2 are currently being investigated in this regard. The use of IGRA would improve the diagnosis of extrapulmonary tuberculosis and LTBI.

Keyword

Interferon-gamma release assays; Latent tuberculosis; Sensitivity; Specificity

MeSH Terms

Adult
BCG Vaccine
Child
Diagnosis
Humans
Interferon-gamma Release Tests*
Interferon-gamma*
Interleukin-2
Korea
Latent Tuberculosis
Mycobacterium tuberculosis
Necrosis
Sensitivity and Specificity
Skin Tests
T-Lymphocytes
Tuberculin
Tuberculosis
Tuberculosis, Pulmonary
BCG Vaccine
Interferon-gamma
Interleukin-2
Tuberculin

Reference

1. Mazurek GH, Jereb JA, Vernon A, LoBue P, Goldberg S, Castro K. Updated guidelines for using interferon gamma release assays to detect mycobacterium tuberculosis infection - United States, 2010. MMWR Recomm Rep. 2010; 59:1–25.

2. Korean guidelines for tuberculosis. 2nd ed. 2014 Joint Committee for the Revision of Korean Guidelines for Tuberculosis, Korea Centers for Disease Control and Prevention.

3. Lee JY. Diagnosis and treatment of extrapulmonary tuberculosis. Tuberc Respir Dis. 2015; 78:47–55.

4. Fan L, Chen Z, Hao XH, Hu ZY, Xiao HP. Interferon-gamma release assays for the diagnosis of extrapulmonary tuberculosis: a systematic review and meta-analysis. FEMS Immunol Med Microbiol. 2012; 65:456–466.

5. Kim SH, Choi SJ, Kim HB, Kim NJ, Oh MD, Choe KW. Diagnostic usefulness of a T-cell based assay for extrapulmonary tuberculosis. Arch Intern Med. 2007; 167:2255–2259.

6. Cho OH, Park KH, Kim SM, Park SJ, Moon SM, Chong YP, et al. Diagnostic performance of T-SPOT.TB for extrapulmonary tuberculosis according to the site of infection. J Infect. 2011; 63:362–369.

7. Kim YK, Uh Y, Lee NS, Cho MY, Eom M, Kim HY. Whole-blood interferon-gamma release assay for diagnosis of tuberculous lymphadenitis. Tohoku J Exp Med. 2011; 224:189–193.

8. Marais BJ, Gie RP, Schaaf HS, Beyers N, Donald PR, Starke JR. Childhood pulmonary tuberculosis: old wisdom and new challenges. Am J Respir Crit Care Med. 2006; 173:1078–1090.

9. Marais BJ, Gie RP, Schaaf HS, Hesseling AC, Obihara CC, Nelson LJ, et al. The clinical epidemiology of childhood pulmonary tuberculosis: a critical review of literature from the pre-chemotherapy era. Int J Tuberc Lung Dis. 2004; 8:278–285.

10. Perez-Velez CM, Marais BJ. Tuberculosis in children. N Engl J Med. 2012; 367:348.

11. Newton SM, Brent AJ, Anderson S, Whittaker E, Kampmann B. Paediatric tuberculosis. Lancet Infect Dis. 2008; 8:498–510.

12. Sollai S, Galli L, de Martino M, Chiappini E. Systematic review and meta-analysis on the utility of Interferon-gamma release assays for the diagnosis of Mycobacterium tuberculosis infection in children: a 2013 update. BMC Infect Dis. 2014; 14:Suppl 1. S6.

13. Hochberg MC, Lebwohl MG, Plevy SE, Hobbs KF, Yocum DE. The benefit/risk profile of TNF-blocking agents: findings of a consensus panel. Semin Arthritis Rheum. 2005; 34:819–836.

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

15. Quesniaux VF, Jacobs M, Allie N, Grivennikov S, Nedospasov SA, Garcia I, et al. TNF in host resistance to tuberculosis infection. Curr Dir Autoimmun. 2010; 11:157–179.

16. Murdaca G, Spanò F, Contatore M, Guastalla A, Penza E, Magnani O, et al. Infection risk associated with anti-TNF-α agents: a review. Expert Opin Drug Saf. 2015; 14:571–582.

17. Shim TS. Diagnosis and treatment of latent tuberculosis infection due to initiation of anti-TNF therapy. Tuberc Respir Dis (Seoul). 2014; 76:261–268.

18. Smith R, Cattamanchi A, Steingart KR, Denkinger C, Dheda K, Winthrop KL, et al. Interferon-γ release assays for diagnosis of latent tuberculosis infection: evidence in immune-mediated inflammatory disorders. Curr Opin Rheumatol. 2011; 23:377–384.

19. Chiappini E, Fossi F, Bonsignori F, Sollai S, Galli L, de Martino M. Utility of interferon-γ release assay results to monitor anti-tubercular treatment in adults and children. Clin Ther. 2012; 34:1041–1048.

20. Kim KH, Lee SW, Chung WT, Kim BG, Woo KS, Han JY, et al. Serial interferon-gamma release assays for the diagnosis of latent tuberculosis infection in patients treated with immunosuppressive agents. Korean J Lab Med. 2011; 31:271–278.

21. Hang NT, Matsushita I, Shimbo T, Hong le T, Tam do B, Lien LT, et al. Association between tuberculosis recurrence and interferon-γ response during treatment. J Infect. 2014; 69:616–626.

22. Diel R, Loddenkemper R, Nienhaus A. Predictive value of interferon-γ release assays and tuberculin skin testing for progression from latent TB infection to disease state: a meta-analysis. Chest. 2012; 142:63–75.

23. Mamishi S, Pourakbari B, Teymuri M, Rubbo PA, Tuaillon E, Keshtkar AA, et al. Diagnostic accuracy of IL-2 for the diagnosis of latent tuberculosis: a systematic review and meta-analysis. Eur J Clin Microbiol Infect Dis. 2014; 33:2111–2119.

24. Blauenfeldt T, Heyckendorf J, Graff Jensen S, Lange C, Drabe C, Hermansen TS, et al. Development of a one-step probe based molecular assay for rapid immunodiagnosis of infection with M. tuberculosis using dried blood spots. PLoS One. 2014; 9:e105628.