Antinuclear antibody (ANA) testing is used in the diagnostic evaluation of various autoimmune diseases, including connective tissue diseases such as systemic lupus erythematosus (SLE), Sjögren syndrome, and systemic sclerosis (SSc).
Initial testing for autoimmune connective tissue diseases (also referred to as systemic autoimmune rheumatic diseases, or SARDs) should include tests for C-reactive protein (CRP), ANAs, rheumatoid factor, and cyclic citrullinated peptide antibodies.
If ANA results are positive, follow-up or confirmatory testing may be guided by the pattern(s) observed and/or the patient’s clinical presentation.
Diagnostic Issues:
Autoimmune connective tissue diseases may present with similar features, making diagnosis difficult. Possible diagnoses may include:
- Inflammatory myopathies
- Mixed connective tissue disease
- SSc
- Sjögren syndrome
- SLE
- Undifferentiated connective tissue disease
ANA with reflex by immunofluorescent assay (IFA) (based on ANA patterns) may help guide differential diagnosis but may not be specific for individual diseases.
Antigen/antibody complexes affect a variety of organs in connective tissue diseases, which frequently leads to a multisystem disease presentation. ANA antibodies are the most common antibodies and may precede the onset of connective tissue disease. Although certain antibodies may show specificity for certain diseases (eg, SSA 52, SSA 60, and SSB antibodies for Sjögren syndrome), ANA antibodies are not specific for connective tissue disease, and may also be associated with infectious diseases, cancers, other autoimmune disorders (eg, autoimmune liver disease), and advanced age, and may even be present in healthy patients.
Patterns:
Homogeneous distribution of the bound antibodies is indicative of systemic lupus erythematosus (SLE). A speckled pattern is strongly related to SLE, but it may also occur in patients with mixed connective tissue disease, Sjögren's syndrome, polymyositis or scleroderma. Peripheral fluorescence can be observed in patients with connective tissue diseases. A nucleolar pattern has been described in patients with overlapping scleroderma and polymyositis/ dermatomyositis syndromes and with systemic scleroderma, especially for those with renal involvement. In patients with the limited cutaneous form of systemic sclerosis staining of the centromeres can be detected.
ANA by HEp-2
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