What lab tests are included in a lupus workup?

Lupus Laboratory Workup

A comprehensive lupus workup should include routine laboratory tests (CBC, serum creatinine, proteinuria, urinary sediment) and immunological tests (serum C3/C4, anti-dsDNA, anti-Ro/SSA, anti-La/SSB, antiphospholipid antibodies, anti-RNP) as these provide essential prognostic information for disease activity and organ involvement. 1

Initial Testing for Diagnosis

First-Line Testing

• Anti-Nuclear Antibody (ANA): The reference method is indirect immunofluorescence assay (IIFA) on HEp-2 cells 1
  • Screening dilution typically 1:160
  • Report should include pattern and highest dilution showing reactivity
  • Sensitivity for SLE approaches 100%, but specificity is low

Second-Line Testing (if ANA positive)

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

  • Highly specific for SLE (40-80% of patients)
  • Preferred methods: Farr assay or Crithidia luciliae immunofluorescence test (CLIFT) for highest specificity 1, 2
  • Results should be reported quantitatively

• Extractable Nuclear Antigens (ENA) panel:

  • Anti-Ro/SSA: Associated with photosensitivity, subacute cutaneous lupus, neonatal lupus
  • Anti-La/SSB: Often with Sjögren's features
  • Anti-Sm: Highly specific for SLE
  • Anti-RNP: Associated with mixed connective tissue disease
  • Results should be reported separately for each antigen 1

Additional Immunological Testing

• Complement levels:

  • C3 and C4 (decreased in active disease)
  • Anti-C1q antibodies (associated with nephritis)

• Antiphospholipid antibodies:

  • Lupus anticoagulant (LA): Requires specialized coagulation testing 1
  • Anti-cardiolipin antibodies (IgG and IgM)
  • Anti-β2 glycoprotein I antibodies

Routine Laboratory Tests

• Complete Blood Count (CBC):

  • Hemoglobin (anemia)
  • White blood cell count (leukopenia)
  • Platelet count (thrombocytopenia)

• Renal Function Tests:

  • Serum creatinine
  • Urinalysis with microscopic examination
  • Urine protein:creatinine ratio or 24-hour protein
  • Estimated glomerular filtration rate (eGFR)

• Inflammatory Markers:

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

Organ-Specific Testing (as indicated)

• Renal Assessment:

  • Renal biopsy (if significant proteinuria, hematuria, or declining renal function)

• Neurological Assessment:

  • Brain MRI (for neuropsychiatric manifestations)
  • Cerebrospinal fluid analysis

Monitoring Disease Activity

For ongoing monitoring of disease activity, the following tests are most valuable:

• Anti-dsDNA antibody levels
• Complement levels (C3/C4)
• Complete blood count
• Urinalysis and proteinuria quantification
• Serum creatinine

Clinical Pearls and Pitfalls

• Important caveat: ANA testing should only be performed in patients with unexplained involvement of two or more organ systems, not for nonspecific symptoms like fatigue 3, 4
• The odds ratio for flare in asymptomatic patients with elevated anti-dsDNA is 3.0 and with low C3 is 2.0 5
• For monitoring anti-dsDNA levels, use the same method consistently 1
• Lupus anticoagulant testing should be performed before starting anticoagulant therapy or after discontinuation 1
• No single laboratory test can reliably distinguish disease activity levels; combinations of tests provide better assessment 6

Special Considerations

• Pregnancy: Additional monitoring of anti-Ro/SSA, anti-La/SSB, and antiphospholipid antibodies is crucial due to risk of neonatal lupus, congenital heart block, and pregnancy complications 1
• Antiphospholipid syndrome: Requires testing for lupus anticoagulant, anti-cardiolipin, and anti-β2 glycoprotein I antibodies 1