What is the essential blood test for Systemic Lupus Erythematosus (SLE)?

Essential Blood Tests for SLE Diagnosis and Monitoring

The antinuclear antibody (ANA) test is the essential initial screening test for systemic lupus erythematosus (SLE), followed by specific autoantibody tests including anti-dsDNA, anti-Sm, and complement levels (C3, C4) for confirmation in patients with clinical suspicion. 1

Initial Diagnostic Testing

The European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) recommend the following autoantibody and complement testing for SLE:

• At baseline (essential tests):
  • ANA (primary screening test)
  • Anti-dsDNA (highly specific for SLE)
  • Anti-Sm (Smith antigen - highly specific for SLE)
  • Anti-Ro/SSA and anti-La/SSB antibodies
  • Anti-RNP antibodies
  • Anti-phospholipid antibodies
  • Complement components (C3, C4) 2, 1

Importance of ANA Testing

ANA testing serves as the cornerstone for SLE diagnosis for several reasons:

• Most sensitive test for SLE (sensitivity ~98% at 1:80 titer) 3
• Excellent for ruling out SLE when negative 4
• Included as an entry criterion in the 2019 SLE classification criteria 5

However, ANA has limited specificity (92-96% when using healthy controls, but lower when using patients with multiple medical problems) 3, which necessitates additional confirmatory testing.

Confirmatory Testing

When ANA is positive, the following confirmatory tests should be performed:

1. Anti-dsDNA antibodies:

   • Highly specific for SLE (specificity 96-100%) 3
   • Useful for monitoring disease activity 1
   • Different testing methods have varying specificity:
     • ELISA: ~90% specificity
     • ELiA: 95.9% specificity
     • CLIFT (Crithidia luciliae immunofluorescence test): 96-97% specificity 1

2. Anti-Sm antibodies:

   • Highly specific for SLE 4
   • Strong confirmatory value even in patients unlikely to have SLE 4

3. Complement levels (C3, C4):

   • Low levels often indicate active disease
   • Important for monitoring disease activity and response to treatment 2, 1

Additional Laboratory Testing

Beyond autoantibody testing, other essential laboratory tests for SLE patients include:

• Complete blood count (CBC):

  • To detect cytopenias (leukopenia, lymphopenia, thrombocytopenia, anemia) 1

• Renal function tests:

  • Serum creatinine (or eGFR)
  • Urinalysis
  • Urine protein/creatinine ratio
  • Essential for detecting lupus nephritis 1

• Cardiovascular risk assessment:

  • Blood cholesterol
  • Blood glucose 2

Monitoring and Follow-up Testing

For ongoing monitoring of SLE patients:

• In patients with inactive disease: laboratory assessments every 6-12 months 2, 1
• In patients with active disease: more frequent monitoring based on clinical status 1
• Re-evaluation of anti-dsDNA and complement levels (C3, C4) to assess disease activity/remission 2
• Re-evaluation of anti-phospholipid antibodies prior to pregnancy, surgery, transplant, estrogen-containing treatments, or with new neurological/vascular events 2
• Re-evaluation of anti-Ro and anti-La antibodies before pregnancy 2

Clinical Pearls and Pitfalls

• Pitfall: ANA can be positive in healthy individuals (4-8% at titers ≥1:160) and in patients with other conditions (6-12% at titers ≥1:160) 3
• Pearl: Anti-dsDNA and anti-Sm antibodies have strong confirmatory power for SLE due to their high specificity 4
• Pitfall: Patients on anticoagulant therapy may have interfering results for lupus anticoagulant testing 2
• Pearl: For patients with unexplained positive ANA at high titers (≥1:160), further evaluation is warranted even if initially asymptomatic 1
• Pitfall: Negative ANA does not completely exclude SLE; if clinical suspicion is high, consider repeat testing in 3-6 months 1

By following this structured approach to laboratory testing, clinicians can effectively diagnose SLE and monitor disease activity to optimize patient outcomes.