What does a Quantiferon (Interferon-Gamma Release Assay) result of mitogen minus Nil (Negative Internal Control) of 9.96 and Nil of 0.04 indicate?

Interpretation of QuantiFERON-TB Gold Test Results with Mitogen Minus NIL of 9.96 and NIL of 0.04

The mitogen minus NIL value of 9.96 and NIL value of 0.04 indicate a valid QuantiFERON-TB Gold test with a robust immune response to the mitogen control and very low background interferon-gamma production, suggesting proper test performance and a reliable result.

Understanding the Components of the Result

NIL Value (0.04 IU/mL)

• The NIL value represents the negative control tube containing heparin alone without TB antigens 1
• A NIL value of 0.04 IU/mL is well within normal limits (typically <8.0 IU/mL), indicating minimal background interferon-gamma production 1
• This low NIL value suggests absence of non-specific immune activation and contributes to test validity 2

Mitogen Minus NIL Value (9.96 IU/mL)

• The mitogen serves as a positive control to verify immune cell functionality and ability to produce interferon-gamma 2
• A mitogen minus NIL value of 9.96 IU/mL is well above the minimum threshold of 1.5 IU/mL required for a valid test 2
• This robust response indicates proper immune cell function and test reliability 2

Significance of These Values

Test Validity

• For a QuantiFERON test to be considered valid, the mitogen minus NIL value should be >1.5 IU/mL 2
• The value of 9.96 IU/mL greatly exceeds this threshold, indicating excellent test validity 2
• The low NIL value (0.04 IU/mL) further confirms minimal background interference 1

Immune Function Assessment

• A strong mitogen response (9.96 IU/mL) indicates intact cell-mediated immunity 3
• Studies have shown that patients with robust mitogen responses (>2 IU/mL) have more reliable test results and better clinical outcomes compared to those with weak responses 3
• The strong mitogen response in this case suggests the patient is not immunosuppressed, which increases confidence in the test result 2

Clinical Implications

Interpretation Algorithm

1. First, verify test validity:

   • NIL value (0.04) is well below the acceptable limit of 8.0 IU/mL ✓
   • Mitogen minus NIL (9.96) is well above the required 1.5 IU/mL threshold ✓

2. To determine TB infection status:

   • Calculate TB antigen response (TB antigen minus NIL)
   • Calculate percentage tuberculin response: (tuberculin - nil) / (mitogen - nil) × 100
   • Apply appropriate cut-offs based on patient risk factors 2

Potential Pitfalls to Avoid

• Do not interpret the mitogen and NIL values in isolation; they must be considered alongside the TB antigen response 1
• A strong mitogen response does not rule out or confirm TB infection by itself; it only validates the test 2
• Serial testing interpretation requires careful consideration of quantitative values, as values near cut-offs may lead to conversions or reversions 4

Important Considerations

• While the test appears technically valid, the final interpretation depends on the TB antigen response value (not provided in the question) 2
• The robust mitogen response suggests that if the test is negative for TB infection, it is likely a true negative rather than a false negative due to immunosuppression 3
• In patients with active TB infection, a strong mitogen response is associated with more reliable test results compared to those with weak responses 3

Advantages of This Result Pattern

• The very low NIL value (0.04) minimizes the risk of false positive results due to non-specific interferon-gamma production 5
• The strong mitogen response (9.96) reduces the likelihood of indeterminate results that can occur with mitogen responses <1.5 IU/mL 2
• This pattern suggests optimal test conditions and reliable results regardless of the final TB infection determination 1