What lab tests are used to diagnose Systemic Lupus Erythematosus (SLE)?

Laboratory Tests for Diagnosing Systemic Lupus Erythematosus (SLE)

The diagnosis of SLE requires a comprehensive laboratory workup centered on antinuclear antibody (ANA) testing as the initial screening test, followed by specific autoantibody panels including anti-dsDNA and anti-extractable nuclear antigens. 1

Initial Laboratory Evaluation

Primary Screening Test

• Antinuclear Antibody (ANA)
  • Method: Indirect immunofluorescence on HEp-2 cells (preferred method)
  • Interpretation: Sensitivity for SLE is nearly 100%, but specificity is low 2
  • Positive titer: ≥1:40 warrants further investigation when clinical features suggest SLE 3
  • Note: ANA should only be ordered in patients with unexplained involvement of two or more organ systems 3

Follow-up Tests for ANA-Positive Patients

Essential Autoantibody Panel

• Anti-dsDNA antibodies

  • Methods and specificity:
    • Farr assay (gold standard, highest specificity but requires radioactive material)
    • Crithidia luciliae immunofluorescence test (CLIFT) - 96-97% specificity
    • ELISA - approximately 90% specificity (less preferred for initial diagnosis due to lower specificity) 1, 2
  • Clinical significance: Highly specific for SLE (present in 40-80% of patients) 2

• Anti-extractable nuclear antigens (ENAs)

  • Anti-Sm (Smith): Highly specific for SLE
  • Anti-Ro (SSA): Associated with photosensitivity, neonatal lupus
  • Anti-La (SSB): Associated with Sjögren's syndrome features
  • Anti-RNP: Associated with mixed connective tissue disease 1

• Complement levels

  • C3 and C4: Decreased levels suggest active disease, particularly lupus nephritis
  • CH50: Measures total complement activity 1, 2

Additional Autoantibody Testing

• Anti-phospholipid antibodies
  • Lupus anticoagulant
  • Anti-cardiolipin antibodies (IgG, IgM)
  • Anti-β2 glycoprotein I antibodies
  • Clinical significance: Associated with thrombosis, recurrent pregnancy loss 1, 2

General Laboratory Assessment

Hematologic Tests

• Complete blood count (CBC)
  • Look for: Anemia, leukopenia, lymphopenia, thrombocytopenia

Inflammatory Markers

• Erythrocyte sedimentation rate (ESR)
• C-reactive protein (CRP)
  • Note: CRP may be disproportionately lower than ESR in active SLE 1

Renal Function Tests

• Serum creatinine
• Estimated glomerular filtration rate (eGFR)
• Urinalysis with microscopy
• Urine protein/creatinine ratio (or 24-hour proteinuria) 1

Liver Function Tests

• Albumin, liver enzymes

Laboratory Monitoring Algorithm

1. Initial Presentation with Suspected SLE:

   • ANA testing (if involvement of ≥2 organ systems)
   • If ANA positive → proceed with specific antibody testing
   • If ANA negative but strong clinical suspicion → consider repeat testing in 3-6 months 1

2. ANA Positive Patients:

   • Test for: anti-dsDNA, anti-ENA panel (Sm, Ro, La, RNP), complement levels (C3, C4), anti-phospholipid antibodies 1
   • Perform baseline CBC, renal and liver function tests

3. Monitoring Established SLE:

   • Anti-dsDNA and complement levels (C3, C4) every 3-6 months and during flares
   • Use same laboratory and method for serial anti-dsDNA measurements 1
   • CBC, renal function, urinalysis every 6-12 months in stable patients 1
   • More frequent monitoring (every 3 months) for patients with nephritis 1

Important Considerations

• Test Interpretation Caveats:

  • Anti-dsDNA antibodies can be found in other conditions besides SLE 1
  • Different anti-dsDNA testing methods may yield discordant results 1
  • No single test is 100% sensitive and specific for SLE diagnosis 1

• When to Repeat Testing:

  • Anti-phospholipid antibodies: Before pregnancy, surgery, transplant, or when starting estrogen therapy 1
  • Anti-Ro/La: Before pregnancy (risk of neonatal lupus) 1
  • Anti-dsDNA/complement: To assess disease activity/remission 1

• Newer Biomarkers:

  • Anti-nucleosome antibodies: Promising for diagnosis
  • Anti-C1q antibodies: Useful for monitoring nephritis activity 2
  • Urinary MCP1: May help monitor nephritis activity 2

By following this systematic laboratory approach, clinicians can effectively diagnose SLE and monitor disease activity to guide treatment decisions that ultimately impact patient morbidity and mortality.