Test Code LAB4233 QUANTIFERON-TB GOLD PLUS
Specimen Type
Whole Blood in Dark Green Heparin tube.
Collection Instructions
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Collect a minimum of 5mL blood specimens by venipuncture preferably into two (2) dark green lithium-heparin tubes or one - 6mL tall dark green lithium heparin tube observing routine safety precautions.
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Hold blood at room temperature (20–25°C) between 15 minutes and 3 hours after collection
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Place lithium-heparin tubes into the designated, refrigerated (2-8°C) rack for QFTs to be processed later (See Specimen Aliquoting and Centrifugation)
Note: After room temperature hold, blood can be refrigerated (2-8°C) for 16 to 48 hours. Samples stored outside of this time and temperature range may give unreliable or indertminate results.
Specimen Volume
5 ml
Blood can be collect useing either two - 4 mL (short tube) or one - 6 ml (tall tube) Lithium Heparin Whole Blood (Dark Green, No Gel) tubes.
Turnaround Time
4 Days
Test Schedule
Tuesday and Friday.
Specimen Processing
Specimen Aliquoting: (At Kootenai Lab we do this at 1900 to encourage batching)
- Ensure Dark Green top tubes have incubated for 16-48 hrs refrigerated (2 to 8°C).
- Allow tube to Equiibrate to room temperature (approximately 30 minutes).
- Print labels for tubes while specimens are warming to roome temperature
- Invert tubes to remix specimens before transfer.
- Pipette 1 mL of blood into each of the four different colored (4) QFT- Plus Tubes. (Grey, Green, Yellow and Purple tops).
- Firmly shake the tubes 10 times. * Important: Simple inversion is not enough. Tubes should be mixed firmly enough to ensure the entire inner surface of the tube is coated with blood to solubilize antigen on the tube walls.
- Label each of the 4 tubes with patient label.
- Place samples in the 37°C Incubator for 16 to 24 hours.
- Document the date, time and number of tubes (number of patients x4) on the QFT Processing Log.
Specimen Centrifugation:
- Ensure specimens have incubated for 16 to 24 hours at 37°C. *Important: Over-Incubation will cause erroneous results. It is important to have all samples centriged before 24 hours to ensure specimen quaility and accurate results.
- Centrifuge specimens for 15 minutes at 2000 - 3200 RPM.
- Remove specimens form centrifuge and place them in Special Chemistry rack for analysis.
- Document the date, time and number of tubes centrifuges on the QFT Processing log.
Method
Enzyme-Linked Immunosorbent Assay (ELISA)
Reference Ranges
Expected Result: Negative
Test Components
QuantiFERON-Tb Gold Plus Result
TB1 Ag minus Nil Result
TB2 Ag minus Nil Result
Mitogen minus Nil Result
Nil Result
CPT Code
86481
Result Interpretation
QFT-Plus results are interpreted using the following criteria:
Nil (IU/mL) |
TB1 minus Nil (IU/mL) |
TB2 minus Nil (IU/mL) |
Mitogen minus Nil (IU/mL)1 |
QFT Result |
Report/Interpretation |
<8.0 |
>0.35 and >25% of Nil |
Any |
Any |
Positive2 |
M. tuberculosis infection likely |
Any |
>0.35 and >25% of Nil |
||||
< 0.35 OR >0.35 and <25% of Nil |
< 0.35 OR >0.35 and <25% of Nil |
> 0.50 |
Negative |
M. Tuberculosis infection NOT likely |
|
< 0.35 OR >0.35 and <25% of Nil |
< 0.35 OR >0.35 and <25% of Nil |
< 0.50 |
Indeterminate3 |
Likelihood of M. tuberculosis infection cannot be determined |
|
>8.04 |
Any |
1 Responses to the Mitogen positive control (and occasionally TB Antigen) can be outside the range of the microplate reader. This has no impact on test results. Values >10 IU/mL are reported by the QFT software as >10 IU/mL.
2 Where M. tuberculosis infection is not suspected, initially positive results can be confirmed by retesting the original plasma samples in duplicate in the QFT ELISA. If repeat testing of one or both replicates is positive, the test result is considered positive.
3 Refer to Indeterminate Results section for possible causes.
4 In clinical studies, less than 0.25% of subjects had IFN-g levels of > 8.0 IU/mL for the Nil
Control.
The magnitude of the measured IFN‑-γ level cannot be correlated to stage or degree of infection, level of immune responsiveness, or likelihood for progression to active disease. A positive TB response in persons who are negative to Mitogen is rare, but has been seen in patients with TB disease. This indicates the IFN-‑γ response to TB antigens is greater than that to Mitogen, which is possible as the level of Mitogen does not maximally stimulate IFN-‑γ production by lymphocytes.
Indeterminate Results
- Indeterminate results are uncommon and may be related to the immune status of the individual being tested, but may also be related to a number of technical factors:
- Longer than 16 hours from blood draw to incubation at 37°C ± 1°C for samples collected directly into QFT‑-Plus Blood Collection Tubes.
- Blood samples collected in lithium-heparin tube stored longer than 12 hours at room temperature (17–-25°C) prior to transfer to QFT-‑Plus Blood Collection Tubes.
- Storage of filled blood collection tubes outside the recommended temperature range (22°C ± 5°C) prior to 37°C ± 1°C incubation.
- In Blood samples collected in lithium-heparin tube for refrigeration stored outside temperature and time ranges included in “Lithium-Heparin Tube Refrigerated Storage and Handling” procedure.
- Insufficient mixing of blood collection tubes,
- Incomplete washing of the ELISA plate
- If technical issues are suspected with the collection or handling of blood samples, repeat the entire QFT test with new blood specimens.
- Repeating the ELISA testing of stimulated plasmas can be performed if inadequate washing or other procedural deviation with the ELISA test is suspected.
- Indeterminate tests that result from low Mitogen or high Nil values would not be expected to change on repeat unless there was an error with the ELISA testing.
- Indeterminate results should be reported as such. Physicians may choose to redraw a specimen or perform other procedures as appropriate.
Limitations
- Results from QFT-‑Plus testing must be used in conjunction with each individual’s epidemiological history, current medical status, and other diagnostic evaluations.
- Individuals with Nil values greater than 8 IU/mL are classed as “Indeterminate” because a 25% higher response to TB Antigens may be outside the assay measurement range.
- The performance of the USA format of the QFT‑-Plus test has not been extensively evaluated with specimens from the following groups of individuals:
- Individuals who have impaired or altered immune functions, such as those who have HIV infection or AIDS, those who have transplantation managed with immunosuppressive treatment or others who receive immunosuppressive drugs (e.g., corticosteroids, methotrexate, azathioprine, cancer chemotherapy), those who have other clinical conditions, such as diabetes, silicosis, chronic renal failure, and hematological disorders (e.g., leukemia and lymphomas), or those with other specific malignancies (e.g., carcinoma of the head or neck and lung)
- Individuals younger than age 17 years
- Pregnant women
- The predictive value of a positive QFT-‑Plus result in diagnosing M. tuberculosis infection depends on the probability of infection, which is assessed by historical, epidemiological, diagnostic, and other findings.
- A diagnosis of LTBI requires that tuberculosis disease must be excluded by medical evaluation including an assessment of current medical and diagnostic tests for disease as indicated.
- A negative result must be considered with the individual’s medical and historical data relevant to probability of M. tuberculosis infection and potential risk of progression to tuberculosis disease, particularly for individuals with impaired immune function. Negative predictive values are likely to be low for persons suspected to have M. tuberculosis disease and should not be relied on to exclude disease.
- The “Standard” and “High Altitude” blood collection tubes have both been calibrated for use at altitudes as specified in “Specimen Collection and Handling”, page 17. Using either type of tube outside the recommended altitude ranges may result in an incorrect volume of blood draw and lead to an incorrect diagnostic outcome. If using the tubes outside the specified ranges of altitude, or if tubes do not fill to the indicator line, it is recommended to draw blood using a syringe and transfer the blood directly to the QFT‑Plus Blood Collection Tubes manually or draw into a lithium-heparin tube followed by transfer to the QFT-‑Plus Blood Collection Tubes (see section Blood collection into a single lithium-heparin tube and then transfer to QFT-Blood Collection Tubes of the package insert for details).
- Unreliable or indeterminate results may occur due to:
- Deviations from the procedure described in the package insert
- Incorrect transport/handling of blood specimen
- Elevated levels of circulating IFN‑-γ or presence of heterophile antibodies
- Exceeding validated blood times from blood specimen draw to incubation:
- Blood samples collected directly into QFT‑-Plus Blood Collection Tubes stored longer than 16 hours at room temperature (17–-25°C).
- Blood samples collected in lithium-heparin tube stored longer than 12 hours at room temperature (17–-25°C) prior to transfer to QFT‑-Plus Blood Collection Tubes.
- Blood samples collected in lithium-heparin tube for refrigeration stored outside temperature and time ranges included in “Lithium-Heparin Tube Refrigerated Storage and Handling” procedure in the QFT‑-Plus Blood Collection Tubes package insert.