What labs do you order to diagnose Systemic Lupus Erythematosus (SLE)?

Laboratory Testing for Lupus Diagnosis

When investigating for systemic lupus erythematosus (SLE), order a comprehensive baseline panel including ANA, anti-dsDNA, anti-Ro, anti-La, anti-RNP, anti-Sm, anti-phospholipid antibodies, C3, C4, complete blood count, serum creatinine (or eGFR), urinalysis with urine protein/creatinine ratio, ESR, CRP, and serum albumin. 1, 2

Core Autoantibody Panel

Initial Screening

• ANA (Antinuclear Antibody) is the primary screening test with nearly 100% sensitivity for SLE, making it essential for ruling out the disease 3, 4, 5
• ANA should be performed using indirect immunofluorescence on HEp-2 cells, which remains the method of choice 3
• Critical caveat: ANA has low specificity and can be positive in many other conditions and even healthy individuals, so it must be interpreted in the appropriate clinical context 3, 4
• Only order ANA testing when there is unexplained involvement of two or more organ systems, not for nonspecific symptoms like isolated fatigue 4, 5

Confirmatory Autoantibodies

• Anti-dsDNA antibodies are highly specific for SLE (present in 40-80% of patients) and correlate with disease activity, particularly active renal disease 1, 2, 3
• For anti-dsDNA testing, use a double-screening strategy: start with a solid-phase assay (FEIA, CLIA, or ELISA) followed by confirmatory CLIFT (Crithidia luciliae immunofluorescence test) if positive 1
• Anti-Sm antibodies are highly specific for SLE and have prognostic value 1, 2, 6
• Anti-Ro (SSA) and anti-La (SSB) antibodies provide prognostic information and are essential before pregnancy due to neonatal lupus risk 1, 2
• Anti-RNP antibodies may provide additional prognostic information 1, 2
• Anti-phospholipid antibodies (lupus anticoagulant and anti-cardiolipin with beta-2 glycoprotein I-dependent method) identify patients at risk for thrombotic manifestations and pregnancy complications 1, 2, 3

Complement Levels

• C3 and C4 must be measured at baseline 1, 2
• Low complement levels, particularly C3, predict disease flares and correlate with active disease, especially renal involvement 2
• Serial C3/C4 measurements alongside anti-dsDNA help monitor disease activity and remission 1

Routine Laboratory Tests

Hematologic Assessment

• Complete blood count (CBC) detects cytopenias that are common in SLE 1, 2
• Severe anemia associates with organ involvement and worse prognosis 2
• Thrombocytopenia correlates with renal disease and progression to end-stage renal disease 2
• Severe leukopenia and lymphopenia increase infection risk 2

Inflammatory Markers

• ESR (erythrocyte sedimentation rate) should be obtained at baseline and for monitoring 1, 2
• CRP (C-reactive protein) has important clinical utility: SLE patients rarely have elevated CRP during disease flares, so significantly elevated CRP (>5-6 mg/dL) suggests superimposed infection with 80-84% specificity 2

Renal Function Assessment

• Serum creatinine (or eGFR) provides prognostic information about renal involvement 1, 2
• Serum albumin indicates renal involvement and poor prognosis when low 1, 2
• Urinalysis with urine protein/creatinine ratio is essential for detecting and monitoring nephritis 1, 2
• Patients with persistently abnormal urinalysis or elevated creatinine should also have urine microscopy, renal ultrasound, and be considered for renal biopsy 1

Common Pitfalls to Avoid

• Do not order ANA in patients with only nonspecific symptoms like isolated fatigue or malaise—this leads to false positives and unnecessary workups 4, 5
• Do not use ELISA alone for anti-dsDNA in the diagnostic phase due to low specificity; always confirm with CLIFT 1, 3
• Do not repeat ANA testing after a positive result—this is neither appropriate nor cost-effective 1
• Do not assume negative anti-dsDNA rules out lupus nephritis—some patients with membranous lupus nephritis remain anti-dsDNA negative long-term 1
• Do not ignore the clinical context—a positive ANA with titer ≥1:40 requires characteristic multiorgan system involvement to diagnose SLE 4

Monitoring Considerations

For patients with established SLE, repeat testing at 6-12 month intervals should include CBC, ESR, CRP, serum albumin, serum creatinine (or eGFR), and urinalysis with urine protein/creatinine ratio 1. Re-evaluate anti-phospholipid antibodies before pregnancy, surgery, transplant, estrogen-containing treatments, or with new neurological/vascular events 1, 2.