Laboratory Testing for Systemic Lupus Erythematosus
At baseline, order a comprehensive autoantibody panel including ANA, anti-dsDNA, anti-Ro/SSA, anti-La/SSB, anti-RNP, anti-Sm, antiphospholipid antibodies, plus complement levels (C3, C4), complete blood count, inflammatory markers (ESR, CRP), renal function (creatinine/eGFR), urinalysis, and urine protein/creatinine ratio. 1, 2
Initial Diagnostic Laboratory Panel
Autoantibody Testing (Baseline)
- ANA by indirect immunofluorescence on HEp-2 cells is the most sensitive screening test for SLE (nearly 100% sensitivity), making it essential for ruling out the disease 3, 4, 5
- Anti-dsDNA and anti-Sm antibodies are highly specific for SLE and have strong confirmatory power even when clinical suspicion is low 1, 3, 5
- Anti-Ro/SSA, anti-La/SSB, anti-RNP antibodies identify patient subgroups at risk for specific clinical manifestations and should be checked at baseline 1
- Antiphospholipid antibodies (lupus anticoagulant and anti-cardiolipin with beta-2 glycoprotein I-dependent method) identify patients at risk for antiphospholipid syndrome 1, 5
Complement and Hematologic Testing
- C3 and C4 complement levels provide prognostic information and correlate with disease activity, particularly in lupus nephritis 1
- Complete blood count assesses for cytopenias (anemia, thrombocytopenia) which correlate with disease severity 1, 2
- ESR and CRP measure inflammatory activity 1, 2
Renal Assessment
- Serum creatinine or eGFR establishes baseline kidney function 1, 2
- Urinalysis with microscopy detects active urinary sediment 1, 2
- Urine protein/creatinine ratio quantifies proteinuria, a key indicator of lupus nephritis 1, 2
- Serum albumin reflects nephrotic syndrome when low 1
Selective Re-evaluation of Autoantibodies
Do not routinely recheck all autoantibodies—only repeat specific antibodies in defined clinical scenarios. 1, 2
- Antiphospholipid antibodies: Recheck before pregnancy, surgery, transplant, estrogen-containing treatments, or with new neurological/vascular events 1, 2
- Anti-Ro and anti-La antibodies: Recheck before pregnancy to assess neonatal lupus risk 1, 2
- Anti-dsDNA and complement (C3/C4): May be rechecked to support evidence of disease activity or remission, particularly in lupus nephritis 1
Routine Monitoring in Stable Disease
For patients with inactive SLE and no organ damage, perform monitoring labs every 6-12 months. 1, 2
The monitoring panel includes:
- Complete blood count 1, 2
- Erythrocyte sedimentation rate 1, 2
- C-reactive protein 1, 2
- Serum albumin 1, 2
- Serum creatinine or eGFR 1, 2
- Urinalysis and urine protein/creatinine ratio 1, 2
Intensive Monitoring for Lupus Nephritis
Patients with established lupus nephritis require monitoring every 3 months for the first 2-3 years. 1, 2
This includes:
- Urine protein/creatinine ratio or 24-hour proteinuria 1, 2
- Immunological tests (C3, C4, anti-dsDNA) 1, 2
- Urine microscopy 1, 2
- Blood pressure measurement 1, 2
- Serum creatinine/eGFR 1, 2
For persistently abnormal urinalysis or elevated creatinine, obtain renal ultrasound and consider kidney biopsy for definitive diagnosis and prognostic information. 1
Common Pitfalls and Caveats
ANA Testing Limitations
- A negative ANA at titers <1:40 strongly argues against SLE, but positive ANA alone has low specificity and occurs in many conditions and healthy individuals 4, 5
- Never rely solely on ANA without specific antibody testing, as this leads to misdiagnosis 2
- Anti-DFS70 antibodies produce positive ANA but exclude SLE diagnosis when present as the only specificity 6
Anti-dsDNA Assay Selection
- The Farr assay is the gold standard for anti-dsDNA but requires radioactive material 5
- Crithidia luciliae immunofluorescence has high specificity and is preferred for initial diagnosis 5
- ELISA methods have lower specificity and should not be used alone for diagnosis, though quantitative ELISA is acceptable for monitoring 5
- Lack of international standardization across anti-dsDNA assays means results are not directly comparable between laboratories 1
Disease Activity Assessment
- Anti-dsDNA and complement levels correlate with disease activity but are not marketed specifically for monitoring purposes 1
- Use validated disease activity indices (SLEDAI or BILAG) at each visit rather than relying solely on laboratory values 1, 2
- Organ damage should be assessed annually using validated indices like the SLICC Damage Index 2