From the Guidelines
The sensitivity and specificity of Antinuclear Antibody (ANA) tests are approximately 95.8% and 86.2%, respectively, when using a 1:160 dilution as the cut-off point. The ANA test is a valuable tool for screening systemic lupus erythematosus (SLE) due to its high sensitivity, but its specificity is lower, ranging from 40-75%, which can lead to false positives in people without SLE 1. The specificity of ANA tests improves at higher titers (1:160 or greater) and with certain staining patterns. It is essential to interpret ANA test results in the context of clinical manifestations and to use additional assays to assess other parameters, as determined by the clinical context 1.
Key Points to Consider
- The ANA test is highly sensitive, making it an excellent screening tool for SLE, but its specificity is lower, which can lead to false positives 1.
- The specificity of ANA tests improves at higher titers (1:160 or greater) and with certain staining patterns 1.
- A negative ANA test generally excludes SLE, while a positive result requires correlation with clinical findings and additional antibody testing to establish a specific autoimmune diagnosis 1.
- The test's predictive value is highest when ordered for patients with clinical features suggesting autoimmune disease rather than as part of indiscriminate screening 1.
Clinical Implications
- Clinicians should exercise caution when interpreting ANA test results, especially when using a 1:80 cut-off point, as it is associated with a low positive likelihood ratio 1.
- Patients should be preselected using clinical and analytical criteria to increase the ANA pre-test probability, and the laboratory should be provided with pertinent clinical information to assess the results and decide on subsequent studies 1.
- The EULAR/ACR 2019 classification criteria recommend ANA detection using the IFI or a solid-phase ANA screening immunoassay (SPA) with at least equivalent performance, but the lack of precision in the concept "equivalent performance" can lead to the use of SPAs with insufficient specificity in SLE screening 1.
From the Research
Sensitivity and Specificity of Antinuclear Antibody (ANA) Tests
- The sensitivity and specificity of ANA tests can vary depending on the method used and the population being tested 2.
- A study found that the COBAS Core ANA-EIA had a sensitivity of 97% and a specificity of 88% for systemic lupus erythematosus (SLE) patients, while the IFA-ANA had a sensitivity of 90% and a specificity of 99% 2.
- Another study found that the ANA/8 profile had a sensitivity of 100% and a specificity of 98% for SLE patients 3.
- The sensitivity and specificity of ANA tests can also depend on the specific autoantibodies being tested, with some autoantibodies being more sensitive or specific for certain diseases 4, 5.
- For example, anti-dsDNA antibodies are highly specific for SLE, while anti-SSA antibodies are commonly found in patients with Sjogren's syndrome 5.
Factors Affecting Sensitivity and Specificity
- The sensitivity and specificity of ANA tests can be affected by various factors, including the method used, the population being tested, and the specific autoantibodies being tested 2, 3.
- High serum rheumatoid factor (RF) concentrations can decrease the sensitivity of ANA tests 2.
- The presence of certain autoantibodies can evade staining by the IFA approach, despite being present in the patient's serum 4.
- The use of automated enzyme immunoassay (EIA) can increase the sensitivity and specificity of ANA tests, especially in patients with negative ANA-IIF results 4.
Clinical Implications
- The sensitivity and specificity of ANA tests have important clinical implications for the diagnosis and management of systemic autoimmune diseases 6, 5.
- A positive ANA test result should be interpreted in the context of clinical symptoms and other laboratory results 6.
- The use of ANA-specific antibodies and anti-dsDNA results can help to increase the specificity of ANA tests and improve patient management 5.