II. Negative

  1. Normal titer less than 1:20 dilution
  2. See interpretation below regarding titers

III. Positive

  1. Normal patient without underlying abnormality: 3-30%
    1. More common in older women
  2. Rheumatologic Conditions
    1. Systemic Lupus Erythematosus
    2. Rheumatoid Arthritis
    3. Mixed connective tissue disease
    4. Sjogren's Syndrome
    5. Necrotizing Vasculitis
  3. Infection
    1. Tuberculosis
    2. Chronic active hepatitis
    3. Subacute Bacterial Endocarditis
    4. HIV Infection
  4. Miscellaneous Conditions
    1. Type I Diabetes Mellitus
    2. Multiple Sclerosis
    3. Pulmonary fibrosis
    4. Silicone gel implants
    5. Pregnant women
    6. Elderly patients
  5. Medications (Drug induced Lupus Erythematosus)
    1. Phenytoin
    2. Ethosuximide
    3. Primidone
    4. Methyldopa
    5. Hydralazine
    6. Penicillamine
    7. Carbamazepine
    8. Procainamide
    9. Thiazides
    10. Griseofulvin
    11. Chlorpromazine
    12. Isoniazid
    13. Quinidine
    14. Gold Salts
    15. Minocycline

IV. Mechanism

  1. IgG or IgM Antinuclear Antibody (ANA)
  2. Binds to nuclei or nuclear components

V. Screening

  1. Slide test
  2. Uses fixed and permeabilized human HEp-2 cells
  3. Measures direct binding
    1. Patient's serum antibodies to cell nuclei
    2. Specific components of cell nucleus are also bound
      1. See ANA subunits below

VI. Interpretation: Titer (Dilution)

  1. Pretest probability affects interpretation
    1. Primary Care Setting: 2% SLE probability
    2. Rheumatology Setting: 30% SLE probability
  2. Low Positive (1:160 or lower): Low significance
    1. SLE Likelihood: <2% (<26% for rheumatologists)
  3. High Positive (1:320 or higher): Higher significance
    1. SLE Likelihood: 2-17% (32-81% for rheumatologists)
  4. References
    1. Malleson (1997) Arch Dis Child 77:299-304 [PubMed]

VII. Interpretation: ANA Staining Patterns

VIII. Interpretation: ANA Subunits

  1. Systemic Lupus Erythematosus
    1. Anti-dsDNA (Lupus sensitivity: 60%)
      1. Specific for lupus erythematosus
      2. Associated with Lupus Nephritis
      3. Associated with Lupus CNS Involvement
    2. Anti-Smith or Anti-Sm (Lupus sensitivity: 20-30%)
      1. Highly specific for lupus erythematosus
    3. Anti-ribosomal P (Lupus sensitivity: 20-30%)
      1. Highly specific for lupus erythematosus
      2. Associated with Lupus Psychosis
    4. Anti-RNP (Lupus sensitivity: 30-40%)
      1. Associated with lupus disease activity
      2. Seen in all cases mixed connective tissue disease
  2. CREST and Scleroderma
    1. Anti-centromere
      1. Sensitivity for Scleroderma: 22-36%
    2. Scl-70 kD kinetochore (Anti-Topoisomerase I)
      1. Sensitivity for Scleroderma: 22-40%
  3. Polymyositis and Dermatomyositis
    1. Anti-Jo1 (sensitivity: 30%)
      1. Also in Raynaud's Phenomenon, pulmonary fibrosis
    2. Anti-Ku
    3. Anti-Mi2
  4. Non-specific
    1. Anti-histone
      1. Drug-Induced Lupus sensitivity: 90%
      2. Systemic Lupus Erythematosus sensitivity: 50%
    2. Anti-Ro (Anti-SSA)
      1. Sjogren's Syndrome sensitivity: 75%
      2. Systemic Lupus Erythematosus sensitivity: 40%
    3. Anti-La (Anti-SSB)
      1. Sjogren's Syndrome sensitivity: 40%
      2. Systemic Lupus Erythematosus sensitivity: 10-15%
    4. Anti-ssDNA
      1. Non-specific and rarely indicated

IX. References

  1. Gladman in Klippel (1997) Rheumatic Diseases p. 255-6
  2. Peng in Ruddy (2001) Kelley's Rheumatology, p. 161-72
  3. Callegari (1995) Postgrad Med, 97(4):65-74 [PubMed]
  4. Lane (2002) Am Fam Physician 65(6):1073-80 [PubMed]

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Ontology: Antibodies, Antinuclear (C0003243)

Definition (NCI) An autoimmune antibody that is directed against structures within the nucleus of the cell.
Definition (MSH) Autoantibodies directed against various nuclear antigens including DNA, RNA, histones, acidic nuclear proteins, or complexes of these molecular elements. Antinuclear antibodies are found in systemic autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, scleroderma, polymyositis, and mixed connective tissue disease.
Definition (CSP) autoimmune, pathological antibodies against histones, DNA, nuclear RNA, or other components of the cell nucleus.
Concepts Amino Acid, Peptide, or Protein (T116) , Immunologic Factor (T129)
MSH D000974
SnomedCT 165849001, 45530001
English Antibodies, Antinuclear, Antibody, Antinuclear, Antinuclear Antibodies, Antinuclear Antibody, Antinuclear Factor, Antinuclear Factors, Factor, Antinuclear, Factors, Antinuclear, antinuclear autoantibody, ANTINUCLEAR FACTOR, antinuclear antibody, antiDNA autoantibody, antinuclear factor, Antinuclear Autoantibody, Antibodies, Antinuclear [Chemical/Ingredient], antinuclear antibody (ANA), anti-nuclear antibody, antinuclear factors, antinuclear antibodies, antinuclear antibody ana, ana, Anti-nuclear factor, Anti nuclear factor, Antinuclear factors, ANF, ANA, ANA - Anti-nuclear antibody, ANF - Anti-nuclear factor, Anti-nuclear antibody, Antinuclear antibody, Antinuclear factor, Antinuclear antibody (substance)
Swedish Antinukleära antikroppar
Finnish Tumavasta-aineet
Italian Fattore antinucleare, Anticorpo antinucleare, Fattori antinucleari, Anticorpi antinucleari
French ANTICORPS ANTINUCLEAIRES, Facteurs lupiques, Anticorps anti-nucléaires, Anticorps antinucléaires, Facteurs antinucléaires, Facteurs anti-nucléaires, Anticorps antinucléaire, Anticorps anti-nucléaire, ACAN, FAN (Facteur AntiNucléaire)
Portuguese FACTOR ANTINUCLEAR, Anticorpos Antinucleares, Fatores Antinucleares
Japanese 抗体-抗核, 抗DNA抗体, 抗核因子, 蛍光抗核抗体, 抗核抗体
Polish Przeciwciała przeciwjądrowe, Czynniki przeciwjądrowe
Czech antinukleární protilátky, antinukleární faktory, protilátky antinukleární, antinukleární faktor
Spanish FAN, anticuerpo antinuclear (sustancia), anticuerpo antinuclear, factor antinuclear, Anticuerpos Antinucleares, Factores Antinucleares
German Antikörper, antinukleäre, Antinukleäre Antikörper, Antinukleäre Faktoren