Interpretation of Normal NIL in QuantiFERON-TB Gold Test
A normal NIL (negative control) result in the QuantiFERON-TB Gold test indicates the absence of interferon-gamma production in the negative control sample and suggests that the test is technically valid, but by itself does not determine latent tuberculosis infection status. 1
Understanding the NIL Value in QuantiFERON Testing
The NIL value in QuantiFERON testing represents the negative control tube that contains heparin alone without any TB antigens. This control serves as a baseline measurement of interferon-gamma (IFN-γ) production in the absence of stimulation.
Key points about the NIL value:
- It serves as the background measurement against which antigen responses are compared
- A normal NIL value (typically <8.0 IU/mL) indicates proper test performance 1
- The NIL value is used in calculations to determine TB infection status
- A normal NIL is necessary but not sufficient to rule out latent TB infection
Proper Interpretation of QuantiFERON Results
The complete interpretation of a QuantiFERON test requires evaluation of multiple values:
- NIL value: Background IFN-γ production
- TB antigen response: IFN-γ production in response to TB-specific antigens
- Mitogen response: Positive control showing immune cell functionality
The test result is determined by calculating:
- TB Response = (TB antigen value - NIL value)
- Percentage tuberculin response = (tuberculin - nil) / (mitogen - nil) × 100 1
According to CDC guidelines, a positive result requires:
- Both (mitogen - nil) and (tuberculin - nil) >1.5 IU
- Percentage avian difference <10
- Percentage tuberculin response >15 (for high-risk individuals) or >30 (for low-risk individuals) 1
Clinical Significance of Results
The interpretation of QuantiFERON results varies based on patient risk factors:
For High-Risk Individuals:
- Recent immigrants from high TB prevalence countries
- Injection drug users
- Healthcare workers with TB exposure risk
- Residents and employees of prisons and jails
A percentage tuberculin response >15% is considered positive for these groups 1
For Low-Risk Individuals:
- A higher threshold (percentage tuberculin response >30%) is used to define a positive result 1
Potential Pitfalls in Interpretation
Several factors can affect the reliability of QuantiFERON results:
- Blood processing time: Blood must be processed within 12 hours of collection 1
- Immunosuppression: Can lead to indeterminate results due to low mitogen response 2
- Technical factors: Improper handling or processing of specimens can affect results 2
- Cross-reactivity: Certain non-tuberculous mycobacteria (M. kansasii, M. szulgai, and M. marinum) can cause false-positive results 1
Indeterminate Results
An indeterminate result occurs when:
- The mitogen response is inadequate (<1.5 IU/mL) 1
- This suggests potential immunosuppression or technical issues with the test
Indeterminate results provide no useful information regarding TB infection status and should not be used to rule out TB infection 2
Follow-up Actions
When interpreting a normal NIL result:
- Review the complete test results, including TB antigen and mitogen responses
- Consider the individual's risk factors for TB infection
- For indeterminate results, consider repeating the test or using alternative testing methods
- When TB disease is clinically suspected, proceed with additional diagnostic evaluations (chest radiography, bacteriologic studies) regardless of QuantiFERON results 2
Advantages of QuantiFERON Over TST
The QuantiFERON test offers several advantages over tuberculin skin testing:
- Requires only one patient visit
- Results available within 24 hours
- Not affected by BCG vaccination
- Less subject to reader bias and error 1
- Does not boost anamnestic immune responses with repeated testing 1
Remember that while a normal NIL value is necessary for valid test interpretation, the determination of latent TB infection status depends on the relationship between NIL, TB antigen, and mitogen responses.