QuantiFERON®-TB Gold (Client Incubated)

CPT: 86480
Print Share

Test Details

Synonyms

  • Interferon-gamma Release Assay (IGRA) for Mycobacterium tuberculosis

Use

The QuantiFERON®-TB Gold test is an in vitro assay to aid in the diagnosis of both latent and active infection with Mycobacterium tuberculosis.

Limitations

Spontaneous interferon-γ production (independent of TB stimulation) or lack of a response to mitogen (such as that due to anergy or immune suppression) may render the results indeterminate. A negative result should not be used alone to exclude M tuberculosis infection in persons with symptoms or signs suggestive of TB disease. Those who have a negative result, but who are likely to have latent TB infection (LTBI) and who are at greater risk for severe illness or poor outcome in case of TB disease, might require treatment or closer monitoring for disease.1

In healthy persons who have a low likelihood both of M tuberculosis infection and of progression to active tuberculosis if infected, a single positive interferon-γ release assay (IGRA) or tuberculin skin test (TST) result should not be taken as reliable evidence of M tuberculosis infection. Because of the low probability of infection, a false-positive result is more likely. In such situations, the likelihood of M tuberculosis infection and of disease progression should be reassessed, and the initial test results should be confirmed. Repeat testing (using a newly collected specimen), with either the initial test or a different test, may be considered on a case-by-case basis. For such persons, an alternative is to assume, without additional testing, that the initial result is a false positive.2

The QuantiFERON® TB test has been shown to be accurate in HIV-positive individuals with moderately advanced disease, but in the severely immunocompromised the test may be impaired by T-cell anergy.3,4

Active TB disease may result in a negative test as reduction of in vitro IFN-γ release has been described and may be due to suppressive cytokines associated with TB disease.5 Patients with mycobacterial infections, other than tuberculosis, might also be responsive to ESAT-6, CFP-10, and TB7.7, as the genes encoding these proteins are present in M kansasii, M szulgai, and M marinum.6

Methodology

Mycobacterium tuberculosis antigen-stimulated interferon-γ production with detection by enzyme-linked immunosorbent assay (ELISA). Test includes PHA (positive) and nil (negative) controls. This is also known as an interferon-γ release assay (IGRA). QuantiFERON® and QFT® are trademarks of the QIAGEN® Group.

Additional Information

Tuberculosis (TB) is a highly contagious respiratory disease caused by bacteria of the Mycobacterium tuberculosis complex (M tuberculosis, M bovis, and M africanum). In the US, tuberculosis is relatively uncommon, due to public health efforts; however, latent TB infection, which is a noncommunicable, asymptomatic condition, is more common. Latent tuberculosis infection (LTBI) results when a person becomes exposed to M tuberculosis and their body controls, but does not eradicate, the infection. It is estimated that 11 million people in the US have LTBI7 and anticipated that approximately 10% of these will progress to active TB during the course of their lifetime.8 Immunosuppression, as occurs in HIV infection or with certain therapies (eg, TNF-α inhibitors), can result in reactivation of the LTBI and development of infectious tuberculous disease. Diagnosis of LTBI is an important step in preventing reactivation of tuberculosis, particularly in at-risk populations.9-11 Treatment of LTBI can markedly reduce the risk of progression to active disease.12,13

The QuantiFERON®-TB Gold assay has been approved by the FDA as an in vitro test to aid in the diagnosis of M tuberculosis infection. The test uses three recombinant peptides from M tuberculosis (ESAT-6, CFP-10, and TB7.7) to stimulate T-cell interferon-γ production in individuals with M tuberculosis infection. These peptide antigens do not usually stimulate lymphocytes from uninfected, BCG-vaccinated persons without disease or risk for LTBI.3,6,14-40 The test also includes a positive "mitogen" control that demonstrates an individual is capable of mounting an immune response to the Tb-antigens and a negative "nil" control. The interpretation of the test is based on a combination of the Tb minus nil control values as well as appropriate nil and mitogen values.

In the past, the tuberculin skin test (TST or Mantoux reaction) was the only method for assessing TB infection. Although widely used, the TST had a number of limitations that have been addressed in the QuantiFERON®-TB Gold assay. For this laboratory assay, the stimulation of lymphocytes with M tuberculosis antigens occurs in the phlebotomy tube, rather than in the patient's arm. As a result, there is no booster effect from repeated testing (as is the case with the TST). Results of the QuantiFERON®-TB Gold test are available following a single patient visit without the need for a second visit to evaluate the skin test. The in vitro assay is not associated with adverse hypersensitivity reactions. The recombinant antigens chosen as stimulants in this assay are not present in the BCG vaccine; therefore, the assay is more specific and prior BCG vaccination will not cause false positives in this test, as it does in the TST.23,26 In addition, the interpretation of the lab test is more objective than the TST result.

Numerous clinical studies have demonstrated that the interferon-γ release assays are a sensitive and specific method for the assessment of tuberculosis infection (both latent and active disease). The CDC has recommended this test for use in all settings in which skin testing is applicable, including contact investigations, evaluation of recent immigrants, and sequential-testing surveillance programs for infection control (eg, those for health care workers).1 Additional utility may be found in the setting of iatrogenic immunosuppression (eg, anti-TNF therapy for arthritis, Crohn's disease and other conditions thought to be immune-mediated) where the identification of LTBI prior to anti-TNF therapy may allow patients to be treated prophylactically to prevent subsequent active TB disease.11,41,42

A positive result indicates that TB infection is likely and should prompt the same public health and medical interventions as a positive TST result. No reason exists to follow a positive QuantiFERON®-TB Gold result with a TST; alternatively, because of the higher specificity, the QuantiFERON®-TB Gold may have value in excluding a diagnosis of TB infection among individuals with positive TST results caused by nontuberculous mycobacteria, thereby reducing overdiagnosis of TB and guiding clinical management.43 Persons who have a positive QuantiFERON®-TB, regardless of symptoms or signs, should be evaluated for TB disease before LTBI is diagnosed.

There has been some controversy regarding individuals with relatively low positive values. A conference was held in June 2012 to discuss the meaning of these without consensus being reached. Some laboratorians believe the cutoff should be modified--or repeat testing offered--while others believe all patients with positive values should be evaluated without repeat testing.44 (For general guidance: http://www.cdc.gov/tb/)

The majority of healthy adults who have negative QuantiFERON®-TB Gold results are unlikely to have M tuberculosis infection and do not require further evaluation; however, for individuals with recent contact with persons who have infectious TB, negative QuantiFERON®-TB Gold results should be confirmed with a repeat test performed weeks after the end of exposure, as is recommended for a negative TST result.23,26

Specimen Requirements

Specimen

Whole blood

Volume

1 mL x three tubes (see Container)

Minimum Volume

0.8 mL x three tubes

Container

The QuantiFERON® collection kit contains the QuantiFERON® blood tubes and instructions for the collection and handling of (1) gray-top (with white ring), uncoated (nil); (2) red-top (with white ring), TB antigen-coated; (3) purple-top (with white ring), mitogen-coated. A high altitude kit is also available for locations between 3350 and 6150 feet. A cap with a yellow ring differentiates the tubes.

Collection

Refer to collection instructions included with draw kit. Special specimen collection kit contains three gel-barrier tubes as noted above. All three tubes are required for a single test result. Each tube is designed to draw only 1 mL and fill time may be longer than other blood collection tubes. Because of the limited vacuum in these tubes, use a needle and holder (not a butterfly) to collect QuantiFERON® specimens. If a butterfly is required, first collect other required tubes or use another Vacutainer® tube to purge the butterfly line of air and then proceed with drawing the QuantiFERON tubes. Fill tubes to the black fill line on the tube. If a tube is underfilled or overfilled (see kit insert), immediately collect a replacement tube.

Following proper fill, label the tubes appropriately and shake tubes 10 times firmly enough to ensure the entire surface of the tube is coated with blood cells to solubilize the antigen on the tube walls. After shaking, the volume may fall below the fill line. Do not centrifuge or refrigerate specimens.

Return each of the three properly filled, labeled, and shaken tubes to the box labeled "QFT® kit." Seal the top by removing tape from the adhesive. Tubes should be incubated (in an incubator, not a water bath or heat block) upright for 16 to 24 hours at 37°C ± 1°C in the box/kit within 16 hours of collection.

Please indicate date and time of venipuncture on the test request form. If the specimen has been incubated for 16 to 24 hours at 37°C ± 1°C, please mark the top of the specimen box where indicated to denote incubation.

Incubation: If blood is not incubated immediately after collection, remix the tubes by inverting 10 times immediately prior to incubation and within 16 hours of collection. Within 16 hours of collection, incubate the tubes upright in an incubator at 37°C ± 1°C for 16 to 24 hours. The incubator does not require CO2 or humidification. Water baths or heat blocks are not suitable alternatives for a laboratory incubator. Following incubation, forward the tubes to the laboratory at 17°C to 27°C.

Storage Instructions

After incubation, maintain specimen at room temperature (17°C to 27°C). Do not centrifuge, refrigerate, or ship tubes on ice.

Causes for Rejection

Specimen frozen; specimen more than 94 hours old on receipt by lab; unlabeled specimens not in QuantiFERON kit box

Clinical Information

Special Instructions

This test is time-sensitive and specimens must be received in the laboratory within 70 hours after incubation by the client (no more than 94 hours from the time of collection). Specimen collection times will vary depending on logistics from the incubating location to a LabCorp lab. This test requires a special collection kit that may not be available at all PSCs.

To submit QuantiFERON specimens that are not client incubated prior to submission, order QuantiFERON®-TB Gold [182873].

Footnotes

1. Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection, American Thoracic Society. MMWR Recomm Rep. 2000 Jun 9; 49(RR-6):1-51. 10881762
2. Mazurek GH, Jereb J, Vernon A, LoBue P, Goldberg S, Castro K; IGRA Expert Committee; Centers for Disease Control and Prevention (CDC). Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection − United States, 2010. MMWR Recomm Rep. 2010 Jun 25; 59(RR-5):1-25. 20577159
3. Brock I, Ruhwald M, Lundgren B, Westh H, Mathiesen LR, Ravn P. Latent tuberculosis in HIV positive, diagnosed by M tuberculosis-specific interferon gamma test. Respir Res. 2006 Apr 1; 7:56. 16579856
4. Rangaka MX, Wilkinson KA, Seldon R, et al. Effect of HIV-1 infection on T-cell-based and skin test detection of tuberculosis infection. Am J Respir Crit Care Med. 2007 Mar 1; 175(5):514-520. 17158278
5. Hirsch CS, Toossi Z, Othieno C, et al. Depressed T-cell interferon-gamma responses in pulmonary tuberculosis: Analysis of underlying mechanisms and modulation with therapy. J Infect Dis. 1999 Dec; 180(6):2069-2073. 10558973
6. Andersen P, Munk ME, Pollock JM, Doherty TM. Specific immune-based diagnosis of tuberculosis. Lancet. 2000 Sep 23; 356(9235):1099-1104. 11009160
7. Bennett DE, Courval JM, Onorato I, et al. Prevalence of tuberculosis infection in the U.S. population: The National Health and Nutrition Examination Survey, 1999-2000. Am J Respir Crit Care Med. 2008 Feb 1; 177(3):348-355. 17989346
8. Small PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med. 2001 Jul 19; 345(3):189-200. 11463015
9. Horsburgh CR Jr. Priorities for the treatment of latent tuberculosis infection in the United States. N Engl J Med. 2004 May 13; 350(20):2060-2067. 15141044
10. Keane J. TNF-blocking agents and tuberculosis: New drugs illuminate an old topic. Rheumatology (Oxford). 2005 Jun; 44(6):714-720. 15741198
11. Pratt A, Nicholl K, Kay L. Use of the QuantiFERON® TB Gold test as part of a screening programme in patients with RA under consideration for treatment with anti-TNF-alpha agents: The Newcastle (UK) experience. Rheumatology (Oxford). 2007 Jun; 46(6):1035-1036. 17409126
12. Pape JW, Jean SS, Ho JL, Hafner A, Johnson WD Jr. Effect of isoniazid prophylaxis on incidence of active tuberculosis and progression of HIV infection. Lancet. 1993 Jul 31; 342(8866):268-272. 8101302
13. Arend SM, Geluk A, van Meijgaarden KE, et al. Antigenic equivalence of human T-cell responses to Mycobacterium tuberculosis-specific RD1-encoded protein antigens ESAT-6 and culture filtrate protein 10 and to mixtures of synthetic peptides. Infect Immun. 2000 Jun; 68(6):3314-3321. 10816479
14. Arend SM, Andersen P, van Meijgaarden KE, et al. Detection of active tuberculosis infection by T-cell responses to early-secreted antigenic target 6-kDa protein and culture filtrate protein 10. J Infect Dis. 2000 May; 181(5):1850-1854. 10823800
15. Arend SM, Thijsen SF, Leyten EM, et al. Comparison of two interferon-gamma assays and tuberculin skin test for tracing TB contact. Am J Respir Crit Care Med. 2007 Mar 15; 175(6):618-627. 17170386
16. Brock I, Munk ME, Kok-Jensen A, Andersen P. Performance of whole blood IFN-gamma test for tuberculosis diagnosis based on PPD or the specific antigens ESAT-6 and CFP-10. Int J Tuberc Lung Dis. 2001 May; 5(5):462-467. 11336278
17. Brock I, Weldingh K, Lillebaek T, Follmann F, Andersen P. Comparison of tuberculin skin test and new specific blood test in tuberculosis contacts. Am J Respir Crit Care Med., 2004 Jul 1; 170(1):65-69. 15087297
18. Dheda K, Udwadia ZF, Huggett JF, Johnson MA, Rook GA. Utility of the antigen-specific interferon-gamma assay for the management of tuberculosis. Curr Opin Pulm Med. 2005 May; 11(3):195-202. 15818179
19. Diel R, Nienhaus A, Lange C, Meywald-Walter K, Forssbohm M, Schaberg T. Tuberculosis contact investigation with a new, specific blood test in low-incidence population containing a high proportion of BCG vaccinated persons. Resp Res. 2006 May 17; 7:77. 16707012
20. Dogra S, Narang P, Mendiratta DK, et al. Comparison of a whole blood interferon-gamma assay with tuberculin skin testing for the detection of tuberculosis infection in hospitalized children in rural India. J Infect. 2007 Mar; 54(3):267-276. 16733068
21. Doherty TM, Demissie A, Olobo J, et al. Immune responses to the Mycobacterium tuberculosis-specific antigen ESAT-6 signal subclinical infection among contacts of tuberculosis patients. J Clin Microbiol. 2002 Feb; 40(2):704-706. 11826002
22. Ferrara G, Losi M, Meacci M, et al. Routine hospital use of a commercial whole blood interferon-gamma assay for tuberculosis infection. Am J Respir Crit Care Med. 2005 Sep 1; 172(5):631-635. 15961696
23. Funayama K, Tsujimoto A, Mori M, et al. Usefulness of QuantiFERON TB-2G in contact investigation of a tuberculosis outbreak in a university. Kekkaku. 2005 Jul; 80(7):527-534. 16167779
24. Harada N, Nakajima Y, Higuchi K, Sekiya Y, Rothel J, Mori T. Screening for tuberculosis infection using whole-blood interferon-gamma and Mantoux testing among Japanese healthcare workers. Infect Con Hosp Epidemiol. 2006 May; 27(5):442-448. 16671023
25. Kang YA, Lee HW, Yoon HI, et al. Discrepancy between the tuberculin skin test and the whole-blood interferon gamma assay for the diagnosis of latent tuberculosis infection in an intermediate tuberculosis-burden country. JAMA. 2005 Jun 8; 293(22):2756-2761. 15941805
26. Lein AD, von Reyn CF, Ravn P, Horsburgh CR Jr, Alexander LN, Andersen P. Cellular immune responses to ESAT-6 discriminate between patients with pulmonary disease due to Mycobacterium tuberculosis.Clin Diag Lab Immunol. 1999 Jul; 6(4):606-609. 10391871
27. Mori T, Sakatani M, Yamagishi F, et al. Specific detection of tuberculosis infection: An interferon-gamma-based assay using new antigens. Am J Respir Crit Care Med. 2004 Jul 1; 170(1):56-64. 15059788
28. Munk ME, Arend SM, Brock I, Ottenhoff TH, Andersen P. Use of ESAT-6 and CFP-10 antigens for the diagnosis of extrapulmonary tuberculosis. J Infect Dis. 2001 Jan 1; 183(1):175-176. 11106545
29. Nakaoka H, Lawson L, Squire SB, et al. Risk for tuberculosis among children. Emerg Infect Dis. 2006 Sep; 12(9):1383-1388. 17073087
30. Pai M, Riley LW, Colford JM Jr. Interferon-gamma assays in the immunodiagnosis of tuberculosis: A systemic review. Lancet Infect Dis. 2004 Dec; 4(12):761-776. 15567126
31. Pai M, Gokhale K, Joshi R, et al. Mycobacterium tuberculosis infection in health care workers in rural India: Comparison of a whole-blood interferon gamma assay with tuberculin skin testing. JAMA. 2005 Jun 8; 293(22):2746-2755. 15941804
32. Pai M, Joshi R, Dogra S, et al. Serial testing of health care workers for tuberculosis using interferon-gamma assay. Am J Respir Crit Care Med. 2006 Aug 1; 174(3):349-355. 16690977
33. Ravn P, Demissie A, Eguale T, et al. Human T-cell response to the ESAT-6 antigen from Mycobacterium tuberculosis. J Infect Dis. 1999 Mar; 179(3):637-645. 9952370
34. Ravn P, Munk ME, Andersen AB, et al. Reactivation of tuberculosis during immunosuppressive treatment in a patient with a positive QuantiFERON®-RD1 test. Scand J Infect Dis. 2004; 36(6-7):499-501. 15307581
35. Ravn P, Munk ME, Andersen AB, et al. Prospective evaluation of a whole-blood test using Mycobacterium tuberculosis-specific antigens ESAT-6 and CFP10 for diagnosis of active tuberculosis. Clin Diagn Lab Immunol. 2005 Apr; 12(4):491-496. 15817755
36. Rothel JS, Anderson P. Diagnosis of latent Mycobacterium tuberculosis infection: Is the demise of the Mantoux test imminent? Expert Rev Anti Infect Ther. 2005 Dec; 3(6):981-993. 16307510
37. Silverman M, Reynolds D, Kavsak PA, Garay J, Daly A, Davis I. Use of an interferon-gamma based assay to assess bladder cancer patients treated with intravesical BCG and exposed to tuberculosis. Clin Biochem. 2007 Aug; 40(12):913-915. 17512514
38. Whalen CC. Diagnosis of latent tuberculosis infection: Measure for measure. JAMA. 2005 Jun 8; 293(22):2785-2787. 15941809
39. Leyten EM, Prins C, Bossink AW, et al. Effect of tuberculin skin testing on a Mycobacterium tuberculosis-specific interferon-gamma assay. Eur Respir J. 2007 Jun; 29(6):1212-1216. 17215314
40. Wolfe F, Michaud K, Anderson J, Urbansky K. Tuberculosis infection in patients with rheumatoid arthritis and the effect of infliximab therapy. Arthritis Rheum. 2004 Feb; 50(2):372-379. 14872478
41. Efthimiou P, Sood S. QuantiFERON TB Gold test: The new standard for screening of latent tuberculosis in patients with rheumatoid arthritis? Ann Rheum Dis. 2007 Feb; 66(2):276. 17127686
42. Detjen AK, Keil T, Roll S, et al. Interferon-gamma release assays improve the diagnosis of tuberculosis and nontuberculous mycobacterial disease in children in a country with a low incidence of tuberculosis. Clin Infect Dis. 2007 Aug 1; 45(3):322-328. 17599309
43. Comstock GW, Edwards LB, Philip RN, Winn WA. A comparison in the United States of America of two tuberculins, PPD-S and RT 23. Bull World Health Organ. 1964; 31:161-170. 14253239
44. 2012 IGRA Sounding Board. Addressing Variability Around the Cut-point in Serial IGRA Testing. Atlanta, Ga: June 2012.

References

Harada N, Higuchi K, Sekiya Y, Rothel J, Kitoh T, Mori T. Basic characteristics of a novel diagnostic method (QuantiFERON TB-2G) for latent tuberculosis infection with the use of Mycobacterium tuberculosis-specific antigens, ESAT-6 and CFP-10. Kekkaku. 2004 Dec; 79(12):725-735. 15782618
Harada N, Mori T, Shishido S, Higuchi K, Sekiya Y. Usefulness of a novel diagnostic method of tuberculosis infection, QuantiFERON TB-2G, in an outbreak of tuberculosis. Kekkaku. 2004 Nov; 79(11):637-643. 15729888
Matulis G, Jüni P, Villiger PM, Gadola SD. Detection of latent tuberculosis in immunosuppressed patients with autoimmune diseases−Performance of a Mycobacterium tuberculosis antigen specific IFN-gamma assay. Annals Rheum Dis. 2008 Jan; 67(1):84-90. 17644549
Mitashita H, Higuchi K, Higashiyama N, et al. Detection of tuberculosis infection using a whole blood interferon gamma assay in a contact investigation−Evaluation using QuantiFERon TB-2G. Kekkaku. 2005 Aug; 80(8):557-564. 16218445
Mori M, Kurosawa R, Imagawa T, et al. Usefulness of interferon-gamma-based diagnosis of Mycobacterium tuberculosis infection in childhood tuberculosis. Kansenshogaku Zasshi. 2005 Dec; 79(12):937-944. 16444975

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
183244 QuantiFERON Client Incubated 182878 QuantiFERON TB Gold 71773-6
183244 QuantiFERON Client Incubated 183761 QuantiFERON Criteria 8251-1
183244 QuantiFERON Client Incubated 183462 QuantiFERON TB Ag Value IU/mL 46217-6
183244 QuantiFERON Client Incubated 183461 QuantiFERON Nil Value IU/mL 71776-9
183244 QuantiFERON Client Incubated 183465 QuantiFERON Mitogen Value IU/mL 71772-8
183244 QuantiFERON Client Incubated 183463 QFT TB Ag minus Nil Value IU/mL 64084-7
183244 QuantiFERON Client Incubated 182876 Interpretation: 48767-8

For Providers

Please login to order a test.

 

© 2017  Laboratory Corporation of America® Holdings and Lexi-Comp Inc. All Rights Reserved.

CPT Statement/Profile Statement

The LOINC® codes are copyright © 1994-2017, Regenstrief Institute, Inc. and the Logical Observation Identifiers Names and Codes (LOINC) Committee. Permission is granted in perpetuity, without payment of license fees or royalties, to use, copy, or distribute the LOINC® codes for any commercial or non-commercial purpose, subject to the terms under the license agreement found at https://loinc.org/license/. Additional information regarding LOINC® codes can be found at LOINC.org, including the LOINC Manual, which can be downloaded at LOINC.org/downloads/files/LOINCManual.pdf