How are anti-DsDNA (double-stranded deoxyribonucleic acid) and Crithidia tests interpreted to diagnose Systemic Lupus Erythematosus (SLE)?

Interpretation of Anti-dsDNA and Crithidia Tests for SLE Diagnosis

Anti-dsDNA testing should be performed using a double-screening strategy with a solid-phase assay (SPA) first, followed by Crithidia luciliae immunofluorescence test (CLIFT) as confirmation, as this approach maximizes both sensitivity and specificity for SLE diagnosis. 1

Anti-dsDNA Testing Methods and Interpretation

Testing Methods

• Solid Phase Assays (SPAs): ELISA, FEIA, CLIA, multiplex assays

  • Higher sensitivity but lower specificity (ELISA ~90%, ELiA 95.9%) 2
  • Used as initial screening tests

• Crithidia luciliae Immunofluorescence Test (CLIFT):

  • Uses kinetoplast of Crithidia luciliae as dsDNA substrate 3
  • Higher specificity (96-97%) but lower sensitivity 2
  • Considered pathognomonic for SLE 1
  • Serves as confirmation test

Interpretation of Results

1. SPA positive, CLIFT positive:

   • Strong evidence for SLE diagnosis
   • Highest specificity for SLE
   • Associated with active disease, particularly lupus nephritis 3

2. SPA positive, CLIFT negative:

   • Neither confirms nor rules out SLE
   • Requires clinical correlation
   • Consider additional testing (anti-nucleosome antibodies) 1

3. SPA negative, CLIFT positive:

   • Inconsistent result requiring repeat testing
   • If inconsistency persists, diagnosis depends on clinical characteristics
   • Patient should undergo periodic follow-up 1

4. SPA negative, CLIFT negative:

   • Generally rules out SLE diagnosis in absence of strong clinical suspicion
   • If clinical suspicion remains high, consider repeat testing in 3-6 months 2

Clinical Significance and Correlation

• Anti-dsDNA antibodies are highly specific for SLE and included in all classification criteria 4

• Positive results correlate with:

  • Active systemic disease
  • Lupus nephritis (sensitivity 72% for CLIFT, 60% for EIA) 4
  • Disease flares (patients with severe flares show concordant positive results) 4

• Anti-dsDNA titers correlate with ANA patterns:

  • Significant relationship between ANA titers and anti-dsDNA antibodies with coarse speckled pattern 5
  • Anti-dsDNA antibodies rarely detected at ANA titers below 1:320 5

Potential Pitfalls and Considerations

1. Discordance between assays:

   • Occurs in approximately 20% of patients and 33% of visits 4
   • May affect classification and monitoring
   • Consider obtaining both CLIFT and EIA for comprehensive assessment 4

2. False positives:

   • Anti-dsDNA can be positive in conditions other than SLE:
     • Mixed connective tissue disease (20%) 3
     • Chronic hepatitis (rare) 6
     • Rheumatoid arthritis with antinuclear factors (rare) 6

3. ANA correlation:

   • Anti-dsDNA testing should follow positive ANA results 2
   • However, rare cases of SLE with negative ANA but positive anti-dsDNA exist 7
   • Low ANA titers with certain patterns may still warrant anti-dsDNA testing 5

4. Monitoring considerations:

   • Anti-dsDNA useful for monitoring disease activity
   • Re-evaluation necessary to assess disease activity/remission 2
   • ANA testing not recommended for monitoring disease activity 1

By following this structured approach to anti-dsDNA testing and interpretation, clinicians can improve diagnostic accuracy for SLE while minimizing false positives and negatives, ultimately leading to better patient outcomes through appropriate treatment initiation and monitoring.