What are the best tests for diagnosing lupus?

Best Tests for Diagnosing Lupus

The best diagnostic approach for lupus includes antinuclear antibody (ANA) testing as the initial screening test, followed by more specific tests including anti-dsDNA and anti-Sm antibodies to confirm the diagnosis. 1

Initial Screening Test

• ANA testing using indirect immunofluorescence on HEp-2 cells is the most sensitive screening test for lupus with nearly 100% sensitivity, making it the best initial test to rule out SLE 2
• ANA testing should only be performed in patients with unexplained involvement of two or more organ systems, as specified by the American College of Rheumatology, due to its low specificity 3
• A positive ANA titer (particularly >1:160) warrants further specific testing 4

Confirmatory Tests

• Anti-double stranded DNA (anti-dsDNA) antibodies:

  • Highly specific for SLE (40-80% of patients) 2
  • The Farr assay is considered the gold standard method for anti-dsDNA detection, though immunofluorescence on Crithidia Luciliae can be used as an alternative due to its high specificity 2
  • ELISA methods should be used cautiously in the diagnostic phase due to lower specificity 2

• Anti-Smith (anti-Sm) antibody:

  • Highly specific for SLE and has strong confirmatory power even in patients unlikely to have the disease 5, 1
  • Should be included in the panel of tests for suspected SLE 1

Additional Specific Antibody Tests

• Anti-extractable nuclear antigens (ENA) including:

  • Anti-Ro/SSA and anti-La/SSB antibodies 1
  • Anti-RNP antibodies 1
  • These help identify subgroups of patients at risk for specific clinical manifestations 2

• Antiphospholipid antibodies:

  • Lupus anticoagulant (LA) testing using dilute Russell's viper venom time (dRVVT) as first choice and sensitive aPTT as second test 1
  • Anti-cardiolipin antibodies with beta2-glycoprotein I-dependent method 2

Monitoring Tests

• Anti-dsDNA antibody levels (quantitative) are useful for monitoring disease activity, particularly in patients with nephritis 2
• Complement levels (C3, C4) should be monitored regularly 1
• Complete blood count (CBC) 1
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) 4
• Urinalysis and urine protein/creatinine ratio 1

Testing Protocol

1. Start with ANA testing in patients with suggestive clinical features (photosensitive rash, symmetric inflammatory joint pain, unexplained cytopenias, multisystem inflammatory disease) 6
2. If ANA is positive (especially at titers >1:160), proceed with specific antibody testing:
   • Anti-dsDNA
   • Anti-Sm
   • Anti-ENA panel (Ro/La/RNP)
   • Complement levels (C3, C4)
3. For patients with suspected antiphospholipid syndrome, add:
   • Lupus anticoagulant testing
   • Anti-cardiolipin antibodies

Important Considerations and Pitfalls

• ANA has high sensitivity but low specificity - positive results are common in other autoimmune diseases and even healthy individuals 2, 3
• Anti-dsDNA ELISA methods may yield false positives; confirmation with Farr assay or Crithidia method is recommended for questionable results 4
• Patients with persistent, characteristic multisystem involvement but negative ANA should be evaluated for possible ANA-negative lupus 3
• Serial monitoring should be done using the same laboratory and assay method due to significant inter-laboratory and inter-method variability 4
• Lupus anticoagulant testing should be performed before starting anticoagulant therapy or after a sufficient period following discontinuation 1