What laboratory tests are used to diagnose lupus?

Laboratory Tests for Lupus Diagnosis

The diagnostic workup for lupus should begin with antinuclear antibody (ANA) testing as the initial screening test, followed by a comprehensive autoantibody panel including anti-dsDNA, anti-Sm, anti-Ro, anti-La, anti-RNP, and antiphospholipid antibodies, along with complement levels (C3, C4), complete blood count, and urinalysis with urine protein/creatinine ratio. 1, 2

Initial Screening Test

• ANA testing is the primary screening test with nearly 100% sensitivity for systemic lupus erythematosus (SLE), making it the best test for ruling out the disease 1, 3, 4
• Indirect immunofluorescence on HEp-2 cells remains the method of choice for ANA detection 5
• An ANA titer of 1:40 or greater with characteristic multiorgan system involvement supports the diagnosis, though ANA alone has low specificity since it can be present in other conditions and even healthy individuals 3, 4

Critical caveat: Only order ANA testing in patients with unexplained involvement of two or more organ systems, as the low disease prevalence in primary care makes the test poorly predictive in asymptomatic patients 3

Confirmatory Autoantibody Panel

Highly Specific Antibodies

• Anti-dsDNA antibodies are highly specific for SLE (present in 40-80% of patients) and correlate with disease activity, particularly active renal disease 2, 5

  • The Farr assay is the gold standard method, though immunofluorescence on Crithidia luciliae is an acceptable alternative for diagnosis due to high specificity 5
  • Avoid ELISA for initial diagnosis due to low specificity, but it can be used for quantitative monitoring 5

• Anti-Sm (Smith antigen) antibodies are highly specific for SLE and have strong confirmatory power even in patients unlikely to have the disease 1, 2, 4

Prognostic Antibodies

• 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

Antiphospholipid Antibodies

• Lupus anticoagulant (LA) testing using dilute Russell's viper venom time (dRVVT) as the first test and sensitive aPTT as the second test 6, 1
• Anti-cardiolipin antibodies with beta-2 glycoprotein I-dependent methods 5
• These identify patients at risk for antiphospholipid syndrome, thrombotic manifestations, and pregnancy complications 2, 5

Important technical considerations for LA testing:

• Blood must be collected before starting anticoagulant therapy or after sufficient discontinuation period 6, 1
• Use fresh venous blood in 0.109 M sodium citrate (9:1 ratio) with double centrifugation 6
• Positive LA results must be repeated after >12 weeks to confirm persistence 6

Complement Levels

• C3 and C4 levels are essential at baseline, as low complement (particularly C3) predicts flares and correlates with active disease, especially renal involvement 2
• These should be monitored regularly throughout the disease course 1, 2

Routine Laboratory Tests

Hematologic Assessment

• Complete blood count (CBC) to detect cytopenias 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) is recommended at baseline and for monitoring 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 2
• Serum albumin indicates renal involvement, with low levels being a negative prognostic factor 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 have urine microscopy and be considered for renal biopsy 2

Sequential Testing Algorithm

For patients with suspected lupus based on clinical presentation:

1. Order ANA as initial screening test 1, 3, 4
2. If ANA positive (≥1:40), proceed with comprehensive autoantibody panel: anti-dsDNA, anti-Sm, anti-Ro, anti-La, anti-RNP, and antiphospholipid antibodies 1, 2
3. Simultaneously obtain complement levels (C3, C4), CBC, ESR, CRP, serum creatinine, serum albumin, and urinalysis with urine protein/creatinine ratio 2
4. If LA positive, repeat testing after >12 weeks to confirm persistence 6

Important pitfall: Patients with characteristic multisystem involvement but ANA titer <1:40 may have ANA-negative lupus and should still be evaluated if clinical suspicion remains high 3