What should be the initial test for Systemic Lupus Erythematosus (SLE)?

Initial Testing for Systemic Lupus Erythematosus (SLE)

Antinuclear Antibody (ANA) testing should be the initial test for suspected Systemic Lupus Erythematosus (SLE). 1, 2, 3

ANA Testing Approach

• ANA testing by indirect immunofluorescence assay (IIFA) on HEp-2 cells is the recommended first-line screening test for SLE due to its high sensitivity 2, 3
• A screening dilution of 1:160 is generally suitable for detecting clinically significant ANA, with higher titers (>1:160) having greater clinical specificity (86.2%) while maintaining appropriate sensitivity (95.8%) for systemic autoimmune rheumatic diseases 2
• The pattern and titer of ANA should always be reported as both are clinically significant for diagnosis 2
• ANA testing has the highest sensitivity for SLE and is therefore the best screening assay for ruling out its presence 4

Follow-up Testing After Positive ANA

• If ANA is positive, proceed with specific antibody testing based on the pattern observed 1, 2:

  • For homogeneous pattern: Anti-dsDNA antibody testing is recommended 2
  • For speckled pattern: Testing for specific extractable nuclear antigens (ENA) including anti-Sm, anti-RNP, anti-SSA/Ro, and anti-SSB/La 2

• Anti-dsDNA antibody testing should use two methods for optimal accuracy 2:

  • Crithidia luciliae immunofluorescence test (CLIFT) - offers high clinical specificity
  • Solid phase assays (SPA) such as ELISA - provides higher sensitivity
  • A double-screening strategy using a last-generation SPA first, followed by CLIFT as confirmation, is optimal 1, 2

• Anti-Sm (Smith antigen) testing is highly specific for SLE and has strong confirmatory power 4, 5

Additional Laboratory Testing

• Complete blood count to assess for cytopenias (leukopenia, lymphopenia, thrombocytopenia, hemolytic anemia) 1
• Complement levels (C3, C4) should be measured alongside anti-dsDNA, particularly for monitoring disease activity 2
• Urinalysis to screen for renal involvement 1
• Anti-phospholipid antibodies (aPL) should be tested as they are associated with general disease activity, thrombotic manifestations, and damage development 1

Common Pitfalls and Considerations

• ANA testing is primarily intended for diagnostic purposes, not for monitoring disease progression 2
• Different laboratories may use different methods and cutoffs for ANA testing, affecting result interpretation 2
• In cases of high clinical suspicion, specific antibody testing should be performed regardless of ANA result, as some autoantibodies may be present in ANA-negative patients 2
• Enzyme-linked immunosorbent assay (ELISA) screening for ANA followed by IFA confirmation is a cost-effective approach, with ELISA showing better sensitivity (90-97% vs 80% for IFA) in SLE patients 6

Testing Algorithm

1. Begin with ANA testing by IIFA on HEp-2 cells 2, 3
2. If ANA positive:
   • Determine pattern and titer 2
   • Proceed with specific antibody testing based on pattern 1, 2
   • Test for anti-dsDNA and anti-Sm antibodies regardless of pattern if SLE is clinically suspected 2, 4
3. If ANA negative but strong clinical suspicion remains:
   • Consider testing for specific antibodies that may be present in ANA-negative patients 2, 7
4. Include complement levels (C3, C4) and complete blood count in initial workup 1, 2

Remember that combination sequential testing is the most logical and cost-effective approach for SLE diagnosis 4.