What antibodies are typically positive in Systemic Lupus Erythematosus (SLE) patients?

Antibodies Commonly Positive in Systemic Lupus Erythematosus (SLE)

The most common autoantibodies detected in SLE patients include antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA), anti-Smith (anti-Sm), anti-Ro (SSA), anti-La (SSB), and anti-ribonucleoprotein (anti-RNP) antibodies. 1

Primary Diagnostic Antibodies

Antinuclear Antibodies (ANA)

• Sensitivity: High (entry criterion in EULAR/ACR 2019 classification)
• Specificity: Moderate (74.7%)
• Testing method: Indirect immunofluorescence on HEp-2 cells at titers ≥1:80
• Clinical significance: Required entry criterion for SLE classification, but not specific enough alone for diagnosis 1
• Important note: Not recommended for monitoring disease activity after initial positive result

Anti-dsDNA Antibodies

• Sensitivity: Moderate (66-68%)
• Specificity: High (94-96%)
• Testing methods:
  • Solid Phase Assays (SPA) like ELISA - more sensitive
  • Crithidia luciliae immunofluorescence test (CLIFT) - more specific 1, 2
• Clinical significance:
  • Strong association with lupus nephritis
  • Useful for monitoring disease activity 1
  • Recommended for quantitative follow-up using the same method and laboratory

Additional Specific Antibodies

Anti-Extractable Nuclear Antigens (anti-ENA)

When ANA is positive, confirmatory testing for anti-ENA is recommended. The most common targets include:

1. Anti-Smith (anti-Sm)

   • Highly specific for SLE
   • Targets spliceosome small nuclear ribonucleoproteins 1

2. Anti-Ro/SSA

   • Associated with photosensitivity, subacute cutaneous lupus
   • Associated with neonatal lupus and congenital heart block 1

3. Anti-La/SSB

   • Often co-occurs with anti-Ro
   • Associated with Sjögren's features 1

4. Anti-U1-RNP

   • Associated with mixed connective tissue disease features
   • Target is U1-ribonucleoprotein 1

5. Anti-ribosomal P protein

   • Associated with neuropsychiatric manifestations
   • Less commonly tested but specific for SLE 1

Other Relevant Antibodies

1. Anti-nucleosome antibodies

   • High sensitivity (83.33%) and specificity (96.67%) for SLE
   • May precede anti-dsDNA in pathogenesis
   • Useful for monitoring disease activity in anti-dsDNA negative lupus nephritis 1

2. Anti-histone antibodies

   • More prevalent in lupus nephritis
   • Also common in drug-induced lupus
   • Types: H1, H2A, H2B, H3, and H4 1

3. Anti-C1q antibodies

   • Present in 30-60% of SLE patients
   • Found in almost 100% of patients with active lupus nephritis
   • High negative predictive value for lupus nephritis flares 1

4. Antiphospholipid antibodies

   • Present in 30-40% of SLE patients
   • Include anticardiolipin, anti-β2GP1, and lupus anticoagulant
   • Associated with thrombotic events and pregnancy complications 1, 3

Clinical Approach to Antibody Testing

Diagnostic Algorithm

1. Start with ANA testing (titer ≥1:80)
2. If ANA positive, proceed with:
   • Anti-dsDNA (preferably using both SPA and CLIFT methods)
   • Anti-ENA panel (Sm, Ro/SSA, La/SSB, U1-RNP)
3. Consider additional antibodies based on clinical presentation:
   • Anti-nucleosome if lupus nephritis suspected but anti-dsDNA negative
   • Antiphospholipid antibodies if thrombotic events or pregnancy loss
   • Anti-C1q if monitoring for nephritis activity

Monitoring Algorithm

1. Do not repeat ANA testing for disease monitoring
2. Monitor anti-dsDNA quantitatively using the same method and laboratory
3. Follow complement levels (C3, C4) alongside antibody testing
4. Consider anti-nucleosome or anti-C1q for monitoring nephritis in anti-dsDNA negative patients 1

Common Pitfalls and Caveats

• False positives: Anti-dsDNA can be positive in other conditions including infections and malignancies
• Discrepancies between methods: Different testing methods for the same antibody may yield different results 2
• Serologically active, clinically quiescent: Some patients have elevated antibodies without clinical activity
• Clinically active, serologically quiescent: Some patients with active disease may not show antibody elevation
• Interpretation challenges: A sequential testing strategy (SPA followed by CLIFT for anti-dsDNA) helps minimize false positives 1

Remember that while antibody testing is crucial for diagnosis and monitoring, results must always be interpreted in the clinical context of the patient's presentation.