Rheumatology Book

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Antinuclear AntibodyAka: Antinuclear Antigen, ANA

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  1. Negative
    1. Normal titer less than 1:20 dilution
    2. See interpretation below regarding titers
  2. 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
  3. Mechanism
    1. IgG or IgM antinuclear Antibody (ANA)
    2. Binds to nuclei or nuclear components
  4. 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
  5. 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
  6. Interpretation: ANA Staining Patterns
    1. Systemic Lupus Erythematosus specific patterns
      1. ANA Rim Pattern
      2. ANA Homogenous Pattern
    2. CREST Syndrome and Scleroderma Specific Patterns
      1. ANA Nucleolar Pattern
      2. ANA Centromere Pattern
    3. Non-Specific Patterns
      1. ANA Speckled Pattern
      2. ANA Diffuse Pattern
  7. 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
  8. 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
    4. Lane (2002) Am Fam Physician 65(6):1073

Antibodies, Antinuclear (C0003243)

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.
ConceptsAmino Acid, Peptide, or Protein (T116) , Immunologic Factor (T129)
MSHD000974
EnglishANA, ANA - Anti-nuclear antibody, ANF, ANF - Anti-nuclear factor, Anti nuclear factor, Anti-nuclear antibody, Anti-nuclear factor, antiDNA autoantibody, Antinuclear Antibodies, Antinuclear Antibody, antinuclear autoantibody, Antinuclear factor, Antinuclear Factors
Spanishanticuerpo antinuclear, factor antinuclear, FAN
Parent ConceptsAutoantibodies (C0004358), Non-organ specific antibody (C0443905)
SourcesCSP, CST, MSH, MTH, SCTSPA, SNOMEDCT
Derived from the NIH UMLS (Unified Medical Language System)



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