What are the laboratory tests used for diagnosing Systemic Lupus Erythematosus (SLE)?

Laboratory Diagnosis of Systemic Lupus Erythematosus

The laboratory diagnosis of SLE requires a sequential testing approach starting with ANA screening in patients with multi-organ involvement, followed by confirmatory immunological tests including anti-dsDNA, anti-Sm, complement levels, and anti-ENA antibodies, combined with routine hematologic and renal function assessments. 1, 2

Initial Screening Test

Antinuclear Antibody (ANA) Testing

• ANA is the most sensitive screening test for SLE and should be the first-line laboratory test in patients with unexplained involvement of two or more organ systems 3, 4
• ANA is positive in nearly all cases of SLE, making it excellent for ruling out the disease when negative 5
• Testing should only be performed when clinical suspicion exists (unexplained rashes, arthritis, serositis, neurological manifestations, cytopenias) to avoid false positives in low-prevalence populations 1, 4
• An ANA titer of 1:40 or greater with characteristic multi-organ involvement supports SLE diagnosis 4
• When ANA is negative but clinical suspicion remains high, anti-dsDNA testing may still be pursued 1

Confirmatory Immunological Tests

Anti-dsDNA Antibody Testing

• A double-screening strategy is recommended: perform a solid-phase assay (SPA) such as FEIA, CLIA, or ELISA first, followed by Crithidia luciliae immunofluorescence test (CLIFT) for confirmation 1
• Anti-dsDNA is highly specific for SLE and has strong confirmatory power 3
• When SPA is positive and CLIFT is negative, the result is indeterminate and requires clinical correlation; consider anti-nucleosome antibodies (83.33% sensitivity, 96.67% specificity) in this scenario 1
• When both tests are positive, this strongly confirms SLE diagnosis 1
• Anti-dsDNA should be included in the initial diagnostic workup alongside complement levels 1

Anti-Sm (Smith Antigen) Antibodies

• Anti-Sm is highly specific for SLE and provides strong confirmatory evidence 3
• Should be tested as part of anti-ENA panel when ANA is positive 1

Anti-Extractable Nuclear Antigen (Anti-ENA) Panel

• When ANA is positive, confirmatory anti-ENA testing is recommended 1
• Key targets include: anti-Sm, anti-Ro/SSA, anti-La/SSB, and anti-RNP 1
• Anti-Ro/SSA and anti-La/SSB provide prognostic information for major organ involvement 1

Complement Levels

• Serum C3 and C4 levels should be measured in all suspected SLE cases 1
• Low complement levels correlate with disease activity and major organ involvement 1
• Anti-C1q antibodies are found in 30-60% of SLE patients and nearly 100% of those with active lupus nephritis 1

Antiphospholipid Antibodies

• Test for anticardiolipin, anti-β2GP1, and lupus anticoagulant as 30-40% of SLE patients are positive 1
• These antibodies increase the likelihood of SLE diagnosis when other tests are equivocal 1
• Provide prognostic information for thrombotic complications 1

Routine Laboratory Tests

Complete Blood Count (CBC)

• Essential for detecting cytopenias: anemia, leukopenia, lymphopenia, and thrombocytopenia 1
• These findings correlate with disease activity and prognosis 1

Renal Function Assessment

• Measure serum creatinine, urinalysis with microscopy, and quantify proteinuria 1
• Proteinuria and urinary sediment abnormalities indicate lupus nephritis 1, 2
• These tests provide prognostic information for end-stage renal disease 1

Testing Algorithm

1. Screen with ANA in patients with multi-organ involvement (rash, arthritis, serositis, neurological symptoms, cytopenias) 4, 5

2. If ANA positive (≥1:40), proceed with:

   • Anti-dsDNA (double-screening: SPA then CLIFT) 1
   • Anti-ENA panel (anti-Sm, anti-Ro/SSA, anti-La/SSB, anti-RNP) 1
   • Complement levels (C3, C4) 1
   • Antiphospholipid antibodies 1
   • CBC 1
   • Renal function tests (creatinine, urinalysis, proteinuria) 1

3. If ANA negative but high clinical suspicion, consider anti-dsDNA testing and clinical follow-up 1

4. If anti-dsDNA results are discordant (SPA+/CLIFT-), add anti-nucleosome antibodies and antiphospholipid antibodies 1

Common Pitfalls to Avoid

• Do not order ANA in patients with only nonspecific symptoms (fatigue, malaise) without multi-organ involvement, as the low positive predictive value leads to false positives 4, 5
• Do not use ANA for disease monitoring after initial positive result; it is not cost-effective and does not correlate with activity 1
• Do not rely on a single anti-dsDNA method; the double-screening approach minimizes false positives and negatives 1
• Do not ignore clinical context when interpreting laboratory results; some patients have serologically active but clinically quiescent disease 1
• Do not assume ANA-negative excludes SLE if clinical suspicion is very high; rare ANA-negative SLE exists 4