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Antinuclear antibody

Antinuclear antibodies (ANAs) are a heterogenous class of autoantibodies raised against antigens present in the cell nucleus, including nucleic acids themselves and the enzymes involved in their processing. Under indirect immunofluorescence (IIF) microscopy, four major ANA staining patterns are observed, due to the varying intranuclear distribution of antigenic targets 1:

  • homogenous
    • causative antibodies include those raised against histones, double-stranded (ds)DNA, single-stranded (ss)DNA, and DNA-histone complexes
  • speckled
    • a broad array of antigen specificities generate a speckled pattern, including those raised against U1-RNP, Sm, and La
    • the speckled pattern has three subtypes
  • centromere
    • antibodies raised against centromere proteins A, B and C
  • nucleolar
    • antibodies raised against components of the PM/Scl and 7-2RNP complexes; U3RNP (fibrillarin); RNA polymerases; and Scl70 (topoisomerase I)

ANAs are implicated in the pathophysiology of numerous diseases, including many inflammatory rheumatic diseases. The ANA IIF assay is highly sensitive but minimally specific; low-titer positive ANA results occurs in approximately 13.8% of the general population 2, though some studies report up to 40% prevalence 3. This fact currently lacks any well-described clinical consequences 4.

Loose associations are often made between particular ANA staining patterns and likely underlying autoimmune disorders, but no pattern is completely specific for any single disease. Following a positive ANA result, solid phase assays may be used to detect specific disease-associated autoantibody subtypes to aid in diagnosis.

Grouped by IIF staining pattern, diseases associated with positive ANA titer include 5:

  • homogenous
  • speckled
    • Sm
      • SLE (30-40%)
      • MCTD (0-8%)
    • U1-RNP
      • MCTD (95-100% in high titer with no other ANA subtype present)
      • SLE (26-50%), commonly in conjunction with anti-Sm antibodies 4
      • PSS (11-22%)
      • RA (10%)
      • Sjogren syndrome (3%)
    • SS-A (Ro)
      • Sjogren syndrome without RA (60-70%)
      • SLE (26-50%)
      • neonatal SLE (>95%)
      • PSS (30%)
      • MCTD (50%)
      • PBC (15-19%)
      • Sjogren syndrome with RA (9%)
    • SS-B (La)
      • Sjogren syndrome without RA (40-60%)
      • SLE
      • Sjogren syndrome with RA (5%)
  • centromere
    • centromere proteins
      • CREST syndrome (limited systemic sclerosis) (70-90%)
      • PSS (4-20%)
      • PBC (12%)
  • nucleolar
    • Scl-70
      • PSS (15-43%); associated with more severe organ involvement (e.g. pulmonary fibrosis) 4
  • cytoplasmic
    • Jo-1
      • polymyositis (30%); particularly associated with interstitial lung disease 4
    • mitochondrial
      • PBC (90-100%)
      • autoimmune hepatitis (7-30%)
      • cryptogenic cirrhosis (30%)
      • acute hepatitis
      • viral hepatitis (3%)
      • other liver diseases
      • SLE (5%)
      • Sjogren syndrome and PSS (8%)
Biochemistry

Article information

rID: 81916
Section: Pathology
Synonyms or Alternate Spellings:
  • ANA
  • ANAs
  • antinuclear antibodies
  • anti-nuclear antibodies

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