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ANA-ASSOCIATED CONNECTIVE TISSUE DISORDERS

  • Rheumatologic conditions associated with a +ANA:

    1. Systemic lupus erythematosus (SLE)

    2. Systemic sclerosis (SSc)

    3. Myositis (often ANA-negative; ~50% of dermatomyositis/polymyositis cases are ANA-positive)

    4. Mixed connective tissue disease (MCTD)

    5. Primary Sjögren’s

  • ANA Testing Pearls:

    • - Antinuclear antibodies (ANA) are autoantibodies that bind to the contents of the cell nucleus. The ANA test detects the ANA autoantibodies that are present in the patient’s serum.

    • - ANA can be elevated in many disorders including autoimmune conditions, infection, and malignancy. 20% of healthy women have a positive ANA. Therefore, it is non-specific and should only be sent if clinical suspicion is high for one of the disorders above.

    • - The level of autoantibody is reported as a titer, which is the highest dilution of the serum at which the autoantibodies are still detectable (e.g., 1:640 is more dilute than 1:80, suggesting more autoantibodies are present in the 1:640 sample). The probability of autoimmunity increases with higher ANA titers:

      • ANA ≥1:80 required by EULAR/ACR SLE classification criteria

      • ANA ≥1:640 → 95.8% specific for SLE

    • - If an ELISA-based ANA test is negative but clinical suspicion for CTD high, ask the lab to carry out an immunofluorescence (IF)-microscopy-based ANA test, which is more specific.

TABLE 9.3Test Characteristics & Clinical Associations for ANA & Sub-Serologies

Systemic lupus erythematosus (SLE)

  • Pathogenesis:

    • - Decreased clearance and increased responsiveness to self-nucleic acids → excessive IFNα production by innate immune cells (especially plasmacytoid dendritic cells) → inappropriate activation of autoreactive B cells → autoantibody production, immune complex deposition in skin, ...

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