Can Systemic Lupus Erythematosus (SLE) cause Perinuclear Anti-Neutrophil Cytoplasmic Antibody (P-ANCA) positivity?

P-ANCA Positivity in Systemic Lupus Erythematosus

Yes, Systemic Lupus Erythematosus (SLE) can cause P-ANCA positivity in approximately 25% of patients, though this finding lacks specificity for SLE and does not correlate with disease activity or specific organ involvement. 1, 2

Prevalence of P-ANCA in SLE

• P-ANCA (Perinuclear Anti-Neutrophil Cytoplasmic Antibody) positivity has been reported in 25.4% of SLE patients 2
• The titers of ANCA in SLE patients typically vary from 1:20 to 1:160 2
• In pediatric SLE, P-ANCA has been detected in approximately 16% of cases 3

Relationship Between P-ANCA and SLE

Clinical Significance

• P-ANCA positivity in SLE does not correlate with:
  • Disease activity as measured by SLEDAI (SLE Disease Activity Index) 2
  • Presence of vasculitis 2, 4
  • Renal or CNS involvement 2
  • Specific clinical manifestations 4

Specificity Issues

• Isolated P-ANCA positivity (without MPO-ANCA) can be found in various inflammatory, non-vasculitic conditions 1
• P-ANCA in SLE is less specific than other autoantibodies such as anti-dsDNA, which has a specificity of 90-97% for SLE 5

Antigen Specificity in SLE-Associated ANCA

• When SLE patients test positive for P-ANCA, the target antigens may include:
  • Myeloperoxidase (MPO) - found in 54.5% of ANCA-positive lupus nephritis patients 6
  • Cathepsin G - found in up to 62.1% of lupus nephritis patients 7
  • Lactoferrin - found in 8.4% of lupus nephritis patients 7

Clinical Context for Interpretation

• P-ANCA testing should always be interpreted within the clinical context of the patient 5
• Multiple positive autoantibodies significantly increase SLE likelihood, with ≥3 positive autoantibodies having 99.3% specificity for SLE 5
• ANA testing with a titer of 1:160 with a speckled pattern exceeds the recommended threshold for suspicion of autoimmune disease (specificity 86.2%, sensitivity 95.8%) 5

Important Distinctions in ANCA Testing

• ANCA can be detected by:

  • Indirect immunofluorescence (IIF) - showing cytoplasmic (C-ANCA) and perinuclear (P-ANCA) patterns 1
  • Enzyme-linked immunosorbent assay (ELISA) - for specific antigens like MPO-ANCA and PR3-ANCA 1

• MPO-ANCA is considered more specific than P-ANCA for the diagnosis of vasculitis 1

Clinical Pitfalls and Caveats

• Do not rely solely on P-ANCA for diagnosing SLE - it has poor specificity and sensitivity compared to standard SLE markers like ANA and anti-dsDNA 5, 2
• P-ANCA positivity may be intermittent in patients, limiting its usefulness as a diagnostic test 1
• When evaluating P-ANCA positivity, always confirm with specific antigen testing (MPO, PR3) to improve diagnostic specificity 1
• P-ANCA testing should be part of a comprehensive immunological assessment that includes anti-ENA antibodies, complement levels, and other SLE-specific markers 5

In conclusion, while P-ANCA positivity can occur in SLE patients, it provides limited diagnostic or prognostic value compared to other established SLE biomarkers.