Laboratory Testing for Suspected Systemic Lupus Erythematosus
Begin with antinuclear antibody (ANA) testing as the initial screening test, and if positive, proceed immediately with a comprehensive autoantibody panel including anti-dsDNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, anti-RNP, antiphospholipid antibodies, and complement levels (C3, C4). 1, 2
Initial Diagnostic Laboratory Panel
Autoantibody Testing (Baseline)
- ANA (antinuclear antibody) should be performed first using indirect immunofluorescence assay (IIFA) on HEp-2 cells as the gold standard method 1, 2
- Anti-dsDNA antibodies using a double-screening strategy: solid-phase assay followed by confirmation with Crithidia luciliae immunofluorescence test (CLIFT) for higher specificity 1, 2
- Anti-Sm antibodies (highly specific for SLE) 3, 1, 4
- Anti-Ro/SSA antibodies 3, 1, 2
- Anti-La/SSB antibodies 3, 1, 2
- Anti-RNP antibodies 3, 1, 2
- Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I) 3, 1, 2
Critical pitfall: Relying solely on ANA without further specific antibody testing leads to misdiagnosis, as ANA has low predictive value in primary care populations without typical multisystem clinical symptoms 1, 5
Complement Levels
Hematologic Assessment
- Complete blood count (CBC) to assess for cytopenias (anemia, thrombocytopenia, leukopenia) 3, 1, 2
- Hemoglobin <10 mg/dl is a risk factor for developing lupus nephritis 6
Inflammatory Markers
- Erythrocyte sedimentation rate (ESR) 3, 1, 2
- C-reactive protein (CRP) - note that CRP typically does not rise significantly in lupus flares (unlike infections), making it useful for distinguishing infection from disease activity 1, 7
Renal Function Assessment
- Serum creatinine (or estimated glomerular filtration rate [eGFR]) 3, 1, 2
- Urinalysis with microscopy 3, 1, 2
- Urine protein/creatinine ratio (or 24-hour proteinuria) 3, 1, 2
- Blood urea nitrogen (BUN) 8, 6
- Serum albumin 3, 1
Important caveat: Serum creatinine >1.3 mg/dl is a significant risk factor for developing lupus nephritis and requires aggressive monitoring 6
Additional Baseline Tests
- Blood pressure measurement - systolic BP ≥130 mmHg is associated with developing lupus nephritis 6
- Infection screening (HIV, HCV, HBV, tuberculosis according to local guidelines) 1
Organ-Specific Evaluation When Indicated
Renal Assessment (if abnormal urinalysis or elevated creatinine)
- Urine microscopy for cellular casts 3, 1
- Renal ultrasound 3
- Consider renal biopsy for persistent abnormalities to guide treatment, as approximately 40% of SLE patients develop lupus nephritis 3, 9
Cardiovascular Risk Assessment
Ophthalmologic Assessment
Monitoring Schedule for Established SLE
Patients with Inactive Disease (Every 6-12 Months)
- Complete blood count 3, 2
- Erythrocyte sedimentation rate 3, 2
- C-reactive protein 3, 2
- Serum albumin 3, 2
- Serum creatinine (or eGFR) 3, 2
- Urinalysis and urine protein/creatinine ratio 3, 2
Patients with Established Nephropathy (Every 3 Months for First 2-3 Years)
- Urine protein/creatinine ratio 3, 1
- Immunological tests (C3, C4, anti-dsDNA) 3, 1
- Urine microscopy 3, 1
- Blood pressure 3, 1
Selective Re-evaluation of Autoantibodies
- Antiphospholipid antibodies: before pregnancy, surgery, transplantation, estrogen-containing treatments, or new neurological/vascular events 3, 2
- Anti-Ro and anti-La antibodies: before pregnancy (risk of congenital heart block and neonatal lupus) 3, 2
- Anti-dsDNA and C3/C4: may be repeated to assess disease activity or remission 3, 2
Key Diagnostic Thresholds
- ANA titer ≥1:40 with characteristic multiorgan involvement supports SLE diagnosis 5
- hsCRP >5-6 mg/dl suggests active infection rather than lupus flare (specificity 80-84%) 7
- Anti-dsDNA and anti-Sm positivity are highly specific for SLE 1, 4, 5
- Low C3 (<0.45) and elevated anti-dsDNA correlate with lupus nephritis development 8, 6
Critical monitoring note: Drug-specific monitoring is mandatory for patients on antimalarials, immunosuppressives, or glucocorticoids beyond the standard SLE panel 3, 2