What blood tests are used to diagnose lupus?

Blood Tests for Diagnosing Lupus

The essential blood tests for diagnosing systemic lupus erythematosus (SLE) include antinuclear antibody (ANA) as the initial screening test, followed by specific autoantibody tests including anti-dsDNA, anti-ENA panel, and complement levels. 1, 2, 3

Initial Screening Test

• Antinuclear Antibody (ANA):
  • First-line screening test for suspected SLE
  • Sensitivity: 98% at titers ≥1:80 4
  • Specificity: 92% at titers ≥1:80,96% at titers ≥1:160 4
  • A negative ANA strongly argues against SLE diagnosis 2
  • Higher titers (≥3+) have increased specificity (96.52%) for SLE 5
  • Testing should be limited to patients with clinical features suggestive of SLE (involvement of two or more organ systems) 2

Confirmatory Autoantibody Tests

Anti-dsDNA Antibodies

• Critical for SLE diagnosis and monitoring disease activity
• Should be tested using a double screening approach:
  • First step: Solid phase assay (SPA) - most sensitive method
  • Second step: Crithidia Luciliae Immunofluorescence Test (CLIFT) - most specific method 1
• Specificity: 100% when using healthy controls, 97% when using patients with multiple medical problems 4
• Quantitative assays should be used for monitoring disease activity 1

Anti-ENA (Extractable Nuclear Antigens) Panel

• Should be performed when ANA is positive 1
• Includes testing for:
  • Anti-Smith (Sm) - highly specific for SLE
  • Anti-Ro (SSA)
  • Anti-La (SSB)
  • Anti-RNP
  • Anti-ribosomal P protein
  • Anti-chromatin/nucleosome antibodies 1
• Multiple positive autoantibodies (≥3) have very high specificity (99.3%) for SLE 5

Additional Important Tests

Complement Levels

• C3 and C4 complement levels
• Low levels often indicate active disease, particularly lupus nephritis

Lupus Anticoagulant Testing

• For patients with suspected antiphospholipid syndrome
• Testing includes:
  • Dilute Russell's Viper Venom Time (dRVVT) - first test to consider
  • Sensitive aPTT with low phospholipid content and silica as activator 1, 6
• Requires proper sample collection with double centrifugation 1

Complete Blood Count (CBC)

• To detect cytopenias (leukopenia, lymphopenia, thrombocytopenia, anemia)
• Common in SLE and part of classification criteria

Urinalysis and Renal Function Tests

• To assess for lupus nephritis
• Includes protein/creatinine ratio, urinary sediment examination

Testing Algorithm

1. Initial screening: ANA test for patients with clinical features suggestive of SLE

   • If negative at <1:40: SLE unlikely, pursue other diagnoses 2
   • If positive at ≥1:40: proceed to confirmatory testing

2. Confirmatory testing for positive ANA:

   • Anti-dsDNA (using both SPA and CLIFT methods)
   • Anti-ENA panel
   • Complement levels (C3, C4)
   • CBC, renal function tests, urinalysis

3. Additional specialized testing based on clinical presentation:

   • Lupus anticoagulant and antiphospholipid antibodies for thrombotic events or pregnancy complications
   • Anti-nucleosome antibodies when clinical suspicion remains high despite negative anti-dsDNA 1

Important Considerations

• Avoid inappropriate ANA testing in patients with nonspecific symptoms like fatigue or malaise, as this has limited diagnostic value and may cause unnecessary anxiety 3, 7

• Interpret results in clinical context: While ANA has high sensitivity for SLE, it lacks specificity and can be positive in other autoimmune conditions or even healthy individuals 3

• Consider test limitations: Different laboratory methods have varying sensitivities and specificities; standardization remains challenging 1

• Multiple positive autoantibodies significantly increase the likelihood of SLE diagnosis 5

• Repeat testing may be necessary, particularly for monitoring disease activity with quantitative anti-dsDNA and complement levels 1