What laboratory tests are used to confirm systemic lupus?

Laboratory Tests to Confirm Systemic Lupus Erythematosus

The most essential laboratory tests for confirming systemic lupus erythematosus (SLE) include antinuclear antibody (ANA) testing as the initial screening test, followed by specific autoantibody tests including anti-dsDNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, anti-RNP, and complement levels (C3, C4). 1

Initial Screening Test

• Antinuclear Antibody (ANA):
  • Primary screening test for SLE
  • Should only be ordered in patients with unexplained involvement of two or more organ systems 2
  • Sensitivity of 98% at titer ≥1:80 and 90% at titer ≥1:160 3
  • Specificity of 92% at titer ≥1:80 and 96% at titer ≥1:160 when using healthy controls 3
  • A negative ANA (titer <1:40) usually rules out SLE, though rare cases of ANA-negative SLE exist 2

Confirmatory Autoantibody Tests

After a positive ANA result, the following specific autoantibody tests should be performed:

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

  • Highly specific for SLE (90-97% specificity depending on method) 4
  • Assigned highest score (6 points) in the 2019 ACR/EULAR classification criteria 4
  • Different testing methods have varying specificity:
    • ELISA: ~90% specificity
    • ELiA: 95.9% specificity
    • CLIFT (Crithidia luciliae immunofluorescence test): 96-97% specificity 4
  • Useful for monitoring disease activity 1

• Anti-Sm (Smith) antibody:

  • Highly specific for SLE
  • Present in 5-30% of SLE patients (higher prevalence in Black patients) 4

• Other important autoantibodies:

  • Anti-Ro/SSA
  • Anti-La/SSB
  • Anti-RNP
  • Anti-phospholipid antibodies 1

Complement Testing

• Complement levels:
  • C3 and C4 should be measured at baseline
  • Low complement levels often indicate active disease
  • Useful for monitoring disease activity/remission 1

Additional Laboratory Tests

• Complete blood count (CBC):

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

• Inflammatory markers:

  • Erythrocyte sedimentation rate (ESR)
  • C-reactive protein (CRP)

• Renal function tests:

  • Serum creatinine (or eGFR)
  • Urinalysis and urine protein/creatinine ratio
  • Important for detecting lupus nephritis 1

• Serum albumin

Testing Algorithm for SLE Diagnosis

1. Initial screening: ANA testing in patients with clinical suspicion and involvement of ≥2 organ systems

2. If ANA positive:

   • Proceed with specific autoantibody testing (anti-dsDNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, anti-RNP, anti-phospholipid antibodies)
   • Order complement levels (C3, C4)
   • Perform basic laboratory tests (CBC, ESR, CRP, renal function, urinalysis)

3. If ANA negative but strong clinical suspicion:

   • Consider repeat testing in 3-6 months 1
   • Evaluate for ANA-negative lupus

Monitoring Recommendations

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

Important Considerations

• The combination of multiple testing methods increases specificity and positive predictive value for SLE diagnosis 5
• ANA pattern (especially homogeneous or speckled) provides additional diagnostic value 5
• Quantitative measurement of anti-ENA antibodies does not correlate well with disease activity and is not recommended for routine monitoring 6
• Laboratory results must always be interpreted within the clinical context 4