What is the specificity of a positive anti-double stranded deoxyribonucleic acid (anti-dsDNA) test for systemic lupus erythematosus (SLE)?

Specificity of Anti-dsDNA Antibodies for Systemic Lupus Erythematosus

Anti-dsDNA antibodies have very high specificity for systemic lupus erythematosus (SLE), with specificity rates ranging from 90-96% depending on the testing method used. 1, 2

Understanding Anti-dsDNA Testing Specificity

Anti-dsDNA antibodies are one of the most important immunological markers for SLE diagnosis and monitoring. Their specificity varies by testing method:

• ELISA (Enzyme-Linked Immunosorbent Assay): Specificity of approximately 90% 2
• ELiA (Fluorescence Immunoassay): Specificity of 95.9% 2
• CLIFT (Crithidia luciliae Immunofluorescence Test): Highest specificity, approaching 96-97% 1, 3

The high specificity makes anti-dsDNA antibodies valuable for SLE diagnosis, especially when combined with clinical features and other laboratory findings.

Testing Considerations and Interpretation

Testing Algorithm

1. Start with ANA testing as an entry criterion (required to be positive at ≥1:80 titer by immunofluorescence for SLE classification) 1
2. Follow positive ANA with anti-dsDNA testing using at least one method 1, 4
3. Consider using multiple anti-dsDNA testing methods for increased specificity 3
   • When both RIA and CLIA testing methods are positive in patients with homogeneous or speckled ANA patterns, specificity approaches 100% 3

Important Caveats

• Despite high specificity, anti-dsDNA antibodies can occasionally be found in:

  • Healthy individuals 1
  • Other autoimmune conditions 1
  • Bacterial, viral, and parasitic infections 1
  • Cancer patients 1

• The term "anti-dsDNA" encompasses a heterogeneous group of antibodies with different specificities, not a single uniform entity 1

Optimizing Diagnostic Accuracy

To maximize diagnostic value:

• Combine anti-dsDNA testing with ANA pattern analysis:

  • Homogeneous ANA pattern plus positive anti-dsDNA has the highest predictive value for SLE (82% of patients with this combination have SLE) 3
  • Speckled ANA pattern plus positive anti-dsDNA has the second highest association with SLE 3

• Consider using multiple testing methods:

  • Specificity and positive predictive value increase with the number of positive assay methods 3
  • PPV reaches 100% when all three common methods (RIA, ELISA, CLIA) are positive 3

Beyond Anti-dsDNA: Additional Testing Considerations

When anti-dsDNA results are negative but SLE is still suspected:

• Anti-nucleosome antibodies may be useful, showing higher sensitivity (47.5% vs 37.5%) and specificity (95-100% vs 82.5-97.5%) than anti-dsDNA for SLE diagnosis 5

• Anti-C1q antibodies are found in almost 100% of patients with active lupus nephritis and can help identify this complication 1

• Anti-ENA antibodies (including Smith, Ro, La, and U1-ribonucleoprotein) should be tested when ANA is positive 1, 4

Clinical Correlation

Anti-dsDNA antibodies are not just diagnostic markers but also have clinical significance:

• Higher titers correlate with disease activity in many patients 6
• IgA anti-dsDNA isotype is particularly associated with lupus nephritis and active disease 7
• IgG/IgM ratio of anti-dsDNA antibodies is significantly higher in patients with more active disease 7

In conclusion, while anti-dsDNA antibodies have excellent specificity for SLE (90-96%), their interpretation should be considered alongside clinical presentation, ANA pattern, and potentially other autoantibodies for optimal diagnostic accuracy.