What is the likelihood of a positive double standard deoxyribonucleic acid (DNA) test being normal?

Understanding Double-Stranded DNA Test Results

A positive double-stranded DNA (dsDNA) test has a significant likelihood of being a false positive, with true positive rates varying by testing method, clinical context, and testing strategy.

Testing Methods and Their Reliability

Double-stranded DNA testing can be performed using different methodologies, each with varying sensitivity and specificity:

• Solid Phase Assays (SPA): These include ELISA, FEIA, CLIA, and multiplex assays

  • Higher sensitivity but lower specificity
  • More prone to false positives

• Crithidia Luciliae Immunofluorescence Test (CLIFT):

  • Considered pathognomonic (highly specific)
  • Lower sensitivity
  • Less prone to false positives 1

Double Screening Strategy

The most reliable approach to dsDNA testing involves a double-screening strategy:

1. First test with a solid phase assay (SPA) - more sensitive
2. Confirm with CLIFT - more specific

This approach yields four possible result combinations:

SPA Result	CLIFT Result	Interpretation
Positive	Positive	SLE very likely
Positive	Negative	SLE likely but not confirmed
Negative	Positive	Inconsistent result, requires clinical correlation
Negative	Negative	SLE diagnosis cannot be established [1]

False Positive Rates

False positive rates for dsDNA testing vary significantly depending on:

1. Testing methodology: SPAs have higher false positive rates than CLIFT

2. Clinical context: Higher false positives in patients with:

   • Inflammatory arthritis
   • Patients on biological treatments 2
   • Other autoimmune conditions

3. Quality control factors:

   • Sample handling
   • Laboratory technique
   • Interpretation thresholds 1

Improving Diagnostic Accuracy

To improve diagnostic accuracy:

• Combined testing approach: Using anti-dsDNA and anti-nucleosome antibodies together increases diagnostic accuracy with a positive predictive value of 93.8% 2

• Quality metrics reporting: Important quality metrics include:

  • Limit of detection (LoD95)
  • Limit of blank (LoB)
  • Percentage of target region covered 1

• Clinical correlation: Always interpret results in the context of clinical presentation

Pitfalls and Caveats

• Biological treatments: Can cause false positive anti-dsDNA results without actual drug-induced lupus 2

• Technical factors: Different testing platforms and providers use different cutoffs, z-scores, and normalization controls, leading to inconsistent reporting 1

• Maternal factors: In prenatal testing contexts, maternal DNA contribution can lead to false positives in dsDNA testing 1

• DNA source: The source of DNA (blood vs. saliva vs. buccal) can affect test quality metrics and accuracy 3

In conclusion, while dsDNA testing is valuable, understanding its limitations and implementing proper testing strategies is essential for accurate interpretation. The double screening approach with SPA followed by CLIFT confirmation provides the most reliable results.