What are the most important Systemic Lupus Erythematosus (SLE) antibodies to screen for?

Most Important SLE Antibodies to Screen For

The most important antibodies to screen for in Systemic Lupus Erythematosus (SLE) are ANA as the initial test, followed by anti-dsDNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, anti-RNP, and antiphospholipid antibodies. 1

Initial Screening

1. Antinuclear Antibodies (ANA):

   • Should be the first-line screening test for suspected SLE
   • Only perform when clinical suspicion is present to avoid false positives
   • Sensitivity of 95.8% and specificity of 86.2% for autoimmune disease 1
   • Titers ≤1:320 may be present in healthy individuals and should not be considered definitive evidence of SLE

2. Follow-up Testing After Positive ANA:

   • When ANA is positive, proceed with specific autoantibody testing to confirm diagnosis 1
   • ANA pattern provides valuable diagnostic information:
     • Homogeneous pattern: Highest association with SLE (82% of anti-dsDNA positive patients with this pattern had SLE) 1, 2
     • Speckled pattern: Second highest association with SLE 2

Specific Antibodies for SLE Diagnosis

High Specificity Antibodies

1. Anti-dsDNA:

   • Highly specific for SLE (90-97% specificity depending on method) 1, 3
   • Assigned highest score (6 points) in the 2019 EULAR/ACR classification criteria 3
   • Methods with highest specificity:
     • CLIFT (Crithidia luciliae immunofluorescence test): 96-97% specificity
     • ELISA: approximately 90% specificity
     • ELiA: 95.9% specificity 1

2. Anti-Sm (Smith) Antibodies:

   • Highly specific for SLE (included in diagnostic criteria) 4, 5
   • Present in 5-30% of SLE patients (more prevalent in Black patients) 5
   • Associated with severity and activity of renal involvement 5

Additional Important Antibodies

1. Anti-Ro/SSA and Anti-La/SSB:

   • Part of the extractable nuclear antigens (ENA) panel 4, 1
   • Important for differentiating between distinct autoimmune conditions 1

2. Anti-RNP (Ribonucleoprotein):

   • Present in 25-47% of SLE patients 5
   • High titers are diagnostic of mixed connective tissue disorder (MCTD)
   • Associated with Raynaud's phenomenon and milder renal involvement 5

3. Antiphospholipid Antibodies:

   • Include anticardiolipin, anti-β2GP1, and lupus anticoagulant
   • Present in 30-40% of SLE patients 4
   • Important for assessing thrombotic risk

Monitoring Disease Activity

1. Anti-dsDNA:

   • Useful for monitoring disease activity 4
   • Should use quantitative assay, preferably with same method used in diagnosis
   • Should be performed by the same laboratory for consistency 4

2. Complement Levels (C3, C4, CH50):

   • Should always be used in patient follow-up, even if previously normal 4
   • Low levels associated with disease activity

3. Anti-C1q Antibodies:

   • Present in 30-60% of SLE patients and nearly 100% of patients with active lupus nephritis 4
   • High negative predictive value: patients unlikely to experience nephritis flare in absence of anti-C1q 4

Important Considerations

• ANA testing is not recommended for monitoring disease activity or progression after diagnosis 4
• Some patients show discordance between serological results and clinical characteristics:
  • Serologically active but clinically quiescent SLE
  • Lupus nephritis with negative anti-dsDNA 4
• Anti-nucleosome antibodies can be used to monitor disease activity in patients with lupus nephritis who remain anti-dsDNA negative 4
• Combination testing of multiple methods (e.g., RIA+CLIA) in patients with homogeneous or speckled ANA patterns maximizes specificity and positive predictive value 2

Pitfalls to Avoid

• Relying solely on ANA titers for diagnosis (can be positive in non-autoimmune conditions)
• Repeating ANA testing for monitoring disease activity (not cost-effective) 4
• Using only one method for anti-dsDNA testing (combining methods increases specificity) 2
• Ignoring clinical context when interpreting antibody results
• Failing to consider that high ANA titers (≥1:640) and multiple positive autoantibodies (≥3) significantly increase SLE likelihood 1