From the Guidelines
Antinuclear antibody (ANA) testing should be ordered when there is a high degree of clinical suspicion of systemic autoimmune diseases, particularly systemic lupus erythematosus (SLE), and the patient presents with a constellation of symptoms suggestive of autoimmune disease. The test is most appropriate for patients presenting with symptoms such as unexplained joint pain, skin rashes (especially malar or discoid rashes), photosensitivity, oral ulcers, serositis, unexplained fevers, or multi-system involvement 1. ANA testing is also indicated for patients with Raynaud's phenomenon, unexplained pleuritis or pericarditis, persistent unexplained fatigue with systemic symptoms, or cytopenias without clear cause.
- Key symptoms that may indicate the need for ANA testing include:
- Unexplained joint pain
- Skin rashes (especially malar or discoid rashes)
- Photosensitivity
- Oral ulcers
- Serositis
- Unexplained fevers
- Multi-system involvement
- Raynaud's phenomenon
- Unexplained pleuritis or pericarditis
- Persistent unexplained fatigue with systemic symptoms
- Cytopenias without clear cause The test has high sensitivity but lower specificity for SLE, meaning a negative result helps rule out SLE, while a positive result requires further evaluation, such as testing for anti-ENA, specifically anti-Ro autoantibodies, to help confirm specific diagnoses and guide management decisions 1. ANA testing should not be used as a screening test in patients with vague, non-specific symptoms or in the general population due to the high rate of false positives (up to 15% of healthy individuals may have positive ANA) 1.
- When interpreting ANA results, it is essential to consider the clinical context and the pre-test probability of the patient, as the positive likelihood ratio of ANA detection is low, especially when using the 1:80 cut-off point 1.
- A cut-off point of 1:160 dilution may be more appropriate, as it increases the specificity of the test to 86.2% while maintaining an appropriate sensitivity of 95.8% 1.
- Clinicians should be prepared to order more specific autoantibody tests if the initial ANA is positive, and should accompany the analytical request with as much pertinent clinical information as possible to help the laboratory assess the results and decide on subsequent studies 1.
From the Research
Ordering ANA Level: Key Considerations
- The antinuclear antibody (ANA) test is used to help diagnose patients with clinical symptoms suggestive of possible autoimmune diseases, such as systemic lupus erythematosus (SLE) 2.
- A positive ANA test may also be seen with non-autoimmune inflammatory diseases, including both acute and chronic infections, which can increase the likelihood of a false positive result, especially in children 2.
- The ANA test can be used as an initial screen in patients with non-specific clinical symptoms, such as fever, joint pain, myalgias, fatigue, rash, or anemia, but the results should be interpreted with caution 2, 3.
Clinical Indications for ANA Testing
- ANA testing is recommended for patients with clinical symptoms suggestive of autoimmune diseases, such as SLE, juvenile idiopathic arthritis (JIA), autoimmune hepatitis (AIH), and primary biliary cholangitis (PBC) 4.
- The test can also be used to monitor patients with known autoimmune diseases and to assess the risk of developing autoimmune diseases in healthy individuals 5, 6.
Interpretation of ANA Results
- A positive ANA result can be seen in both autoimmune and non-autoimmune conditions, and the results should be interpreted in the context of the patient's clinical symptoms and other laboratory tests 2, 3.
- The staining patterns on the HEp-2 IFA test can provide additional information about the specificity of the autoantibodies and can help to distinguish between different autoimmune diseases 4.
- The cutoff values for ANA testing may need to be revised, as low concentrations of ANA can be seen in healthy individuals, especially in young people 6.