Initial Blood Tests for Systemic Lupus Erythematosus (SLE) Workup
The initial blood workup for a patient suspected of having SLE should include ANA, anti-dsDNA, anti-Ro, anti-La, anti-RNP, anti-Sm, anti-phospholipid antibodies, complement levels (C3, C4), complete blood count, erythrocyte sedimentation rate, C-reactive protein, serum albumin, serum creatinine, and urinalysis with protein/creatinine ratio. 1, 2
Core Autoantibody and Complement Testing
Primary Tests
- Antinuclear antibody (ANA) - The fundamental screening test for SLE
- Anti-double-stranded DNA (anti-dsDNA) - More specific for SLE
- Complement levels (C3, C4) - Often decreased in active disease
Additional Autoantibody Panel
- Anti-Ro (SSA) antibodies
- Anti-La (SSB) antibodies
- Anti-RNP antibodies
- Anti-Sm antibodies - Highly specific for SLE
- Anti-phospholipid antibodies (including anticardiolipin, anti-β2 glycoprotein I, and lupus anticoagulant)
Standard Laboratory Tests
Hematologic Assessment
- Complete blood count (CBC) - To identify cytopenias (leukopenia, lymphopenia, thrombocytopenia, anemia)
- Erythrocyte sedimentation rate (ESR) - Non-specific marker of inflammation
- C-reactive protein (CRP) - May be less elevated in SLE compared to other inflammatory conditions
Renal Function Assessment
- Serum creatinine (or eGFR) - To assess kidney function
- Serum albumin - May be decreased in nephrotic syndrome
- Urinalysis with urine protein/creatinine ratio - To detect proteinuria and hematuria
Clinical Context for Test Interpretation
When to Consider SLE Testing
- Testing should be performed when patients present with unexplained involvement of two or more organ systems 3
- ANA testing has low predictive value in patients without typical clinical symptoms due to the low prevalence of SLE in primary care populations 3
Interpretation of Results
- ANA titer of 1:40 with characteristic multiorgan involvement may be sufficient for diagnosis 3
- Patients with ANA titer of 1:40 who don't meet full clinical criteria should undergo additional testing for anti-dsDNA and anti-Sm 3
- ANA titer less than 1:40 usually rules out SLE, but patients with persistent characteristic symptoms may have ANA-negative disease 3
Special Considerations
Monitoring Disease Activity
- Anti-dsDNA and complement levels (C3, C4) are particularly useful for monitoring disease activity and response to treatment 1
- These tests should be repeated during follow-up to assess disease status
Additional Testing Based on Clinical Presentation
- For suspected renal involvement: Consider 24-hour urine collection for protein and renal ultrasound 1
- For neuropsychiatric symptoms: Additional neurological workup may be needed 1
- For cardiovascular risk assessment: Lipid profile and blood glucose 1
Pitfalls and Caveats
- Cytopenias in SLE can have multiple causes including disease activity, medications, infections, or rarely, hematologic malignancies 4
- Complete blood count-derived inflammatory markers (neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio) may be elevated in SLE compared to healthy controls but have limited correlation with disease characteristics 5, 6
- High ANA titers (>1:640) may predict SLE flares and should prompt careful monitoring 6
- Patients on immunosuppressive therapy require regular screening for malignancies 4
By systematically ordering and interpreting these blood tests in the context of clinical findings, clinicians can effectively evaluate patients with suspected SLE and determine the need for rheumatology referral.