What does a nil value in the Tuberculin (TB) Gold test indicate?

Understanding the Nil Value in TB Gold Test

The nil value in the TB Gold test represents the background level of interferon-gamma (IFN-γ) in a patient's blood sample without antigen stimulation, and an elevated nil value can lead to an indeterminate test result that provides no useful information about TB infection status. 1

What is the Nil Value?

The TB Gold test (QuantiFERON-TB Gold) is an interferon-gamma release assay (IGRA) that works by:

• Collecting blood in three different tubes:

  • Nil tube (negative control): Contains heparin alone
  • TB antigen tube: Contains peptides from TB-specific antigens (ESAT-6, CFP-10, TB7.7)
  • Mitogen tube (positive control): Contains phytohemaglutinin

• The nil value specifically:

  • Measures the background level of IFN-γ in the patient's blood without stimulation
  • Serves as a baseline for calculating the TB response
  • Is subtracted from the IFN-γ concentration in the antigen-stimulated sample 1

Interpretation of Nil Values

Normal Nil Value

• A normal nil value allows for proper interpretation of the test
• The TB response is calculated as: (IFN-γ in TB antigen tube) - (IFN-γ in nil tube)

Elevated Nil Value

• An elevated nil value (typically >8.0 IU/mL) results in an indeterminate test result
• High background IFN-γ levels can interfere with proper test interpretation
• An indeterminate result provides no useful information about the likelihood of TB infection 1, 2

Clinical Implications of Indeterminate Results Due to High Nil Values

When a TB Gold test is indeterminate due to a high nil value:

1. Follow-up options include:

   • Repeating the test with a new blood specimen
   • Performing a tuberculin skin test (TST)
   • No further testing if clinical suspicion is low 1, 2

2. Causes of elevated nil values may include:

   • Inflammatory conditions
   • Technical errors in specimen collection or processing
   • Improper handling of blood samples 2

3. Case example:

   • There are documented cases where patients with miliary tuberculosis had indeterminate results due to high IFN-γ in the nil control, despite lymphocytopenia 3

Important Considerations

• Blood must be incubated with test antigens within 12 hours of collection for accurate results 1, 2
• Proper storage and processing of samples is critical for test validity
• An indeterminate result should never delay further diagnostic evaluation when TB disease is suspected 1
• If TB disease is suspected, additional diagnostic evaluations (chest radiography, bacteriologic studies, etc.) should be performed regardless of TB Gold test results 2

Clinical Decision Making with Indeterminate Results

For patients with indeterminate TB Gold test results:

• For patients with high clinical suspicion for TB:

  • Proceed with comprehensive TB evaluation including chest radiography, sputum studies, and other appropriate tests
  • Consider repeating the TB Gold test or performing a TST
  • Do not delay treatment decisions while awaiting repeat testing if clinical suspicion is high 1, 2

• For patients with low clinical suspicion for TB:

  • No further testing may be necessary
  • Clinical judgment should guide the decision for additional evaluation 2

Remember that the TB Gold test, like any diagnostic test, has limitations and should be interpreted in the context of the patient's clinical presentation, risk factors, and other diagnostic findings.