What labs are used to diagnose lupus?

Laboratory Tests for Diagnosing Lupus

The essential laboratory tests for diagnosing lupus include ANA, anti-dsDNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, anti-RNP, anti-phospholipid antibodies, and complement levels (C3, C4). 1

Initial Screening Tests

1. Antinuclear Antibody (ANA)

   • Gold standard method: Indirect immunofluorescence (IIF) on HEp-2 cells 2
   • Positive titer: ≥1:80 (required entry criterion for SLE classification) 1
   • Sensitivity: High (>95% for SLE)
   • Specificity: Low (can be positive in healthy individuals)
   • Patterns provide diagnostic clues:
     • Homogeneous: Associated with anti-dsDNA, histones (SLE)
     • Speckled: Associated with anti-Sm, anti-RNP (SLE, MCTD)
     • Nucleolar: Associated with systemic sclerosis
     • Centromere: Associated with limited systemic sclerosis 2

2. Complete Blood Count (CBC)

   • Monitors for cytopenias (anemia, leukopenia, thrombocytopenia)
   • Should be checked every 6-12 months in stable patients 1

3. Erythrocyte Sedimentation Rate (ESR) and C-reactive Protein (CRP)

   • Markers of inflammation
   • CRP often remains low in SLE flares unless infection is present 1

Confirmatory Autoantibody Tests

When ANA is positive, these specific antibodies should be tested:

1. Anti-dsDNA Antibodies

   • Testing strategy: Use solid phase assay (SPA) for screening, followed by Crithidia luciliae immunofluorescence test (CLIFT) for confirmation 1
   • Specificity: 90-97% for SLE
   • Correlates with disease activity and lupus nephritis
   • Fluctuates with disease activity, useful for monitoring 1

2. Anti-Smith (Sm) Antibodies

   • Highly specific for SLE (>95%)
   • Present in 10-30% of SLE patients
   • Remains stable over time 1, 3

3. Anti-Ro/SSA and Anti-La/SSB Antibodies

   • Associated with Sjögren's syndrome and SLE
   • Important to test before pregnancy (risk of neonatal lupus) 1

4. Anti-RNP Antibodies

   • Associated with mixed connective tissue disease and SLE 1

5. Anti-phospholipid Antibodies

   • Includes lupus anticoagulant, anti-cardiolipin, and anti-β2-glycoprotein I
   • Associated with thrombosis and pregnancy complications
   • Should be tested prior to pregnancy, surgery, transplant, or with new neurological/vascular events 1

Complement Studies

1. Complement Levels (C3, C4)

   • Low levels suggest active disease, especially lupus nephritis
   • Should be monitored regularly, even if previously normal 1

2. Anti-C1q Antibodies (specialized test)

   • Present in 30-60% of SLE patients
   • Found in almost 100% of patients with active lupus nephritis
   • High negative predictive value for lupus nephritis flares 1

Renal Function Tests

1. Serum Creatinine and eGFR

   • Monitors kidney function

2. Urinalysis and Urine Protein/Creatinine Ratio

   • Essential for detecting lupus nephritis
   • Should be performed every 6-12 months in stable patients 1

Diagnostic Algorithm

1. Step 1: ANA testing (titer ≥1:80) as entry criterion
2. Step 2: If ANA positive, proceed with specific antibody testing:
   • Anti-dsDNA (SPA followed by CLIFT)
   • Anti-Sm
   • Anti-Ro/SSA, Anti-La/SSB
   • Anti-RNP
   • Anti-phospholipid antibodies
3. Step 3: Complement studies (C3, C4)
4. Step 4: Basic laboratory tests (CBC, ESR, CRP, renal function)

Monitoring Tests

For established SLE patients, the following should be monitored every 6-12 months (more frequently during flares):

• Anti-dsDNA antibodies
• Complement levels (C3, C4)
• CBC
• ESR and CRP
• Serum creatinine/eGFR
• Urinalysis and urine protein/creatinine ratio 1

Common Pitfalls

1. Over-reliance on ANA: A positive ANA alone is insufficient for diagnosis; specific antibodies are needed for confirmation.

2. Failure to retest previously negative patients: Anti-phospholipid antibodies should be retested before pregnancy or surgery; anti-Ro/La before pregnancy; and anti-dsDNA/complement may change with disease activity 1.

3. Misinterpretation of CRP: Unlike other inflammatory conditions, CRP may remain normal in active SLE unless infection is present.

4. Inadequate monitoring: Even patients with inactive disease require regular laboratory monitoring to detect subclinical disease activity.