Lupus Laboratory Testing
Begin with ANA testing by indirect immunofluorescence on HEp-2 cells, and if positive, immediately proceed 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
Initial Screening Approach
- ANA testing serves as the entry point for lupus evaluation due to its high sensitivity for ruling out the disease 1, 2
- The gold standard method is indirect immunofluorescence assay (IIFA) on HEp-2 cells 1, 3
- ANA should only be ordered in patients with unexplained involvement of two or more organ systems to avoid false positives in low-prevalence populations 2
- Do not rely solely on ANA without further specific antibody testing, as this leads to misdiagnosis 4
Comprehensive Autoantibody Panel (If ANA Positive)
The following tests should be ordered simultaneously after a positive ANA 1, 4:
Anti-dsDNA antibodies using a double-screening strategy: solid-phase assay followed by confirmation with Crithidia luciliae immunofluorescence test (CLIFT) for higher specificity 1, 4
Antiphospholipid antibodies including lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I 1, 4, 3
Complement levels (C3 and C4) to assess disease activity 1, 4, 3
Baseline Organ Function Assessment
Renal Evaluation
- Complete urinalysis with microscopy for cellular casts 1, 4
- Urine protein/creatinine ratio 4, 3
- Serum creatinine or estimated glomerular filtration rate (eGFR) 4, 3
- Approximately 40% of SLE patients develop lupus nephritis, and renal biopsy should be considered for persistent abnormalities to guide treatment 1, 5
Hematologic and Inflammatory Markers
- Complete blood count (CBC) to assess for cytopenias 4, 3
- Erythrocyte sedimentation rate (ESR) 4, 3
- C-reactive protein (CRP) 4, 3
- Note: CRP typically remains low in lupus flares but rises significantly with infection (>5-6 mg/dL suggests infection with 80-84% specificity) 6
- Serum albumin 4, 3
Monitoring Schedule for Established SLE
Inactive Disease (Every 6-12 Months)
- Complete blood count 4, 3
- Erythrocyte sedimentation rate 4, 3
- C-reactive protein 4, 3
- Serum albumin 4, 3
- Serum creatinine or eGFR 4, 3
- Urinalysis and urine protein/creatinine ratio 4, 3
Active Nephropathy (Every 3 Months for First 2-3 Years)
- Urine protein/creatinine ratio 1, 4
- Immunological tests (C3, C4, anti-dsDNA) 1, 4
- Urine microscopy 1, 4
- Blood pressure monitoring 1, 4
Selective Autoantibody Re-evaluation
Do not routinely repeat all autoantibodies. Re-test only in specific clinical scenarios 4, 3:
Antiphospholipid antibodies before pregnancy, surgery, transplantation, estrogen-containing treatments, or new neurological/vascular events 1, 4, 3
Anti-Ro and anti-La antibodies before pregnancy due to risk of congenital heart block and neonatal lupus 1, 4, 3
Anti-dsDNA and C3/C4 may be repeated to assess disease activity or remission 1, 3
Critical Diagnostic Thresholds
- ANA titer ≥1:40 with characteristic multiorgan involvement meets diagnostic criteria without additional testing 2
- Anti-dsDNA and anti-Sm positivity are highly specific for SLE and essentially confirm the diagnosis 1, 4
- Patients with persistent multisystem involvement but ANA <1:40 may have ANA-negative lupus and require further evaluation 2
Common Pitfalls to Avoid
- Ordering ANA in patients without multiorgan involvement leads to false positives due to low disease prevalence 2
- Stopping at a positive ANA without the complete autoantibody panel results in missed or delayed diagnosis 4
- Using non-standard ANA methods instead of IIFA on HEp-2 cells reduces diagnostic accuracy 1, 3
- Failing to use CLIFT confirmation for anti-dsDNA decreases specificity 1, 3