The Anti-Nuclear Antibody (ANA!)

Patterns of ANA and Disease Associations

Homogenous pattern

  • Anti dsDNA
    • Specificity for SLE 95% – false positive in some hepatitis
    • Sensitivity 40-60% in SLE
    • One of 11 criteria for SLE
    • Predicts flares: may predate nephritis
  • Anti-Histone
    • Drug-induced lupus (procainamide, hydralazine, aldomet, dilantin, INH, tegretol)
    • Best for negative predictive value

Speckled pattern (ENA or acid extractable nuclear antigens)

  • Anti-Smith
    • 99% specific, 20% sensitive for SLE
  • Anti U1-RNP
    • 30-40% sensitive for SLE (associated with Raynaud’s and less severe clinical course)
    • Mixed connective tissue disease:
      • Nearly 100% sensitive
      • SLE, Raynaud’s, myositis, non-erosive arthritis, puffy hands, esophageal dysmotility, sicca, scleroderma-like
      • Other CTD: 2-5% scleroderma, 24% PM/scleroderma overlap, 4-17% PM/DM
    • Anti Ro (SSA) and La (SSB)
      • In primary Sjogren’s: Anti-SSA 88-96% and Anti SSB 71-87%
        • Associated with increased severity (vasculitis, hypergammaglobulinemia, lympho/leukopenia)
      • SLE: SSA 25%, SSB 10%
      • Neonatal lupus: 90%

Nucleolar (RNA-associated antigens)

  • Anti SCL-70 (Topoisomerase I)
    • 95% of patients with scleroderma – predicts more subacute, progressive, systemic disease
    • Diffuse scleroderma: 25-75% sensitivity, 93% specificity
    • CREST 13%
  • Anti PM-SCL: polymyositis/scleroderma overlap syndromes

Centromere

  • Limited scleroderma: 60-80%
  • Isolated Raynaud’s: 25% – may predict risk of CREST
  • Primary biliary cirrhosis
  • Normal: nearly 1% of female blood donors

Peripheral

  • Antibodies to nuclear envelope, seen with staining for dsDNA in older systems

Cytoplasmic

  • Mitochondrial pattern: primary biliary cirrosis, autoimmune hepatitis, IBD, scleroderma
  • Anti Jo-1 (speckled cytoplasmic)
    • 20-40% of patients with dermatomyositis, polymyositis, mixed PM/DM
    • Higher prevalence of ILD (20-25%)