What labs are recommended to screen for Systemic Lupus Erythematosus (SLE)?

Laboratory Tests for Screening Systemic Lupus Erythematosus (SLE)

The recommended initial screening test for SLE is Antinuclear Antibody (ANA), followed by specific autoantibody tests including anti-dsDNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, anti-RNP, and complement levels (C3, C4) for confirmation in patients with clinical suspicion and involvement of ≥2 organ systems. 1

Initial Screening Test

• Antinuclear Antibody (ANA): This is the first-line screening test for SLE
  • If ANA is negative, SLE is unlikely and further autoantibody testing is generally not recommended except with high clinical suspicion 1
  • A positive ANA with clinical symptoms suggestive of SLE warrants further autoantibody testing

Confirmatory Laboratory Tests

If ANA is positive with clinical symptoms suggestive of SLE, the following tests should be ordered:

1. Anti-double stranded DNA (anti-dsDNA) antibodies:

   • Highly specific for SLE diagnosis (specificity varies by method: ELISA ~90%, ELiA 95.9%, CLIFT 96-97%) 1
   • Particularly associated with lupus nephritis
   • Useful for monitoring disease activity

2. Anti-Smith (anti-Sm) antibodies:

   • Highly specific for SLE
   • Part of the immunological criteria in EULAR/ACR classification

3. Complement levels:

   • C3 and C4 complement components
   • Often inversely correlated with disease activity
   • Low levels suggest active disease

4. Additional autoantibodies:

   • Anti-Ro/SSA and anti-La/SSB antibodies (associated with neonatal lupus) 2
   • Anti-RNP antibodies (may have prognostic value) 2
   • Anti-phospholipid (aPL) antibodies (associated with thrombotic manifestations) 2

Additional Laboratory Tests

• Complete Blood Count (CBC):

  • To detect cytopenias: leukopenia, lymphopenia, thrombocytopenia, anemia 1
  • Severe anemia has been associated with organ involvement and worse prognosis 2
  • Thrombocytopenia has been associated with renal disease and worse prognosis 2

• Renal Function Tests:

  • Serum creatinine (or eGFR)
  • Urinalysis
  • Urine protein/creatinine ratio 2, 1
  • These provide information on the presence and prognosis of renal involvement

• Inflammatory Markers:

  • Erythrocyte Sedimentation Rate (ESR)
  • C-reactive protein (CRP)
    • Note: CRP is more useful for detecting infections than SLE activity 2, 3
    • CRP levels >50 mg/L strongly suggest infection rather than SLE flare 4
    • The ratio of ESR:CRP may help distinguish between SLE flare and infection 5

Clinical Pitfalls and Considerations

• ANA testing limitations:

  • A positive ANA alone is not diagnostic for SLE as it can be found in other autoimmune conditions
  • ANA testing is not recommended for monitoring disease activity 1

• Anti-dsDNA interpretation:

  • Different testing methods have varying specificity
  • A positive CLIFT result has the highest specificity for SLE 1

• Complement level interpretation:

  • Low complement levels may indicate active disease but have no predictive value for the development of disease flares 2

• CRP interpretation:

  • Unlike other inflammatory conditions, SLE rarely causes significantly elevated CRP levels
  • CRP >50 mg/L suggests superimposed infection rather than SLE activity alone 2, 4

• Monitoring frequency:

  • Laboratory assessments should be performed every 6-12 months in patients with inactive SLE
  • More frequent monitoring is needed for active disease 1

By following this structured approach to laboratory testing, clinicians can effectively screen for SLE, confirm the diagnosis, and monitor disease activity to guide treatment decisions and improve patient outcomes.