What is the AC-2 (Antinuclear Antibody) pattern associated with?

AC-2 ANA Pattern: Association with Centromere Antibodies and Limited Systemic Sclerosis

The AC-2 ANA pattern (centromere pattern) is strongly associated with limited systemic sclerosis, particularly the CREST syndrome variant, and is caused by antibodies targeting kinetochore proteins (CENP-A, B, C, F). 1

Clinical Associations of AC-2 Pattern

Primary Disease Associations

• AC-2 pattern is highly specific for limited cutaneous systemic sclerosis (lcSSc), particularly the CREST syndrome variant (Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia) 1, 2
• Present in approximately 70-98% of patients with CREST syndrome 2, 3
• Highly selective marker with sensitivity of 89.1% and specificity of 92.3% for CREST syndrome 4

Secondary Disease Associations

• Primary Raynaud's phenomenon (found in some patients who may later develop limited SSc) 2
• Occasionally seen in other conditions:
  • Primary biliary cirrhosis 5
  • Overlap syndromes involving SSc 5
  • Rarely in systemic lupus erythematosus (SLE) 2
  • Rarely in mixed connective tissue disease (MCTD) 2

Molecular Targets and Pattern Characteristics

• The AC-2 pattern is caused by antibodies targeting kinetochore proteins, primarily:
  • CENP-A, CENP-B, CENP-C, and CENP-F 1
• On HEp-2 cells using indirect immunofluorescence (IIFA), it appears as:
  • Discrete speckled pattern with 40-80 dots distributed throughout interphase nuclei 1
  • During mitosis, the dots align at the centromeric region of chromosomes 2
• Anti-CENP-B antibodies can be specifically measured by ELISA for confirmation 5

Clinical Significance and Prognostic Value

• Presence of anticentromere antibodies is associated with a more favorable prognosis compared to other ANA patterns in systemic sclerosis 6
• Patients with anticentromere antibodies typically have:
  • Less major organ system involvement 6
  • Higher risk of developing pulmonary arterial hypertension (PAH) 7
  • Lower risk of interstitial lung disease compared to other SSc antibody patterns 5
• Higher anti-CENP-B antibody levels correlate with:
  • Greater likelihood of developing CREST features 5
  • Higher association with Sjögren's syndrome when present 5

Laboratory Considerations

• AC-2 pattern is best detected using HEp-2 cells as substrate for IIFA 1
• May be missed when using traditional rodent tissue substrates (kidney, liver) 3
• Significant titers in adults are generally ≥1:40 dilution by IIFA 1
• Confirmation with specific anti-CENP-B ELISA may be helpful in ambiguous cases 5

Clinical Pitfalls and Recommendations

• The centromere pattern may be overlooked when using traditional rodent tissue substrates instead of HEp-2 cells 3
• Patients with positive anticentromere antibodies should be monitored for:
  • Development of limited SSc in those with isolated Raynaud's phenomenon 2
  • Pulmonary arterial hypertension, which is a major cause of mortality in limited SSc 7
• Anticentromere antibodies may coexist with other autoantibodies (particularly anti-SSA/Ro), potentially leading to overlap syndromes 5
• Screening for pulmonary hypertension is particularly important in patients with anticentromere antibodies, as it is a leading cause of death in limited SSc 7