Specificity of ANA Testing for Lupus
The ANA test has relatively poor specificity for systemic lupus erythematosus (SLE), with specificity of only 74.7% at the standard 1:80 titer cutoff and improving to 86.2% at titers ≥1:160. 1
Understanding ANA Specificity
The ANA test is highly sensitive for SLE (approaching 100% sensitivity) but lacks specificity, meaning many positive results occur in patients without lupus. 2, 3
Specificity by Titer Level
- At 1:80 titer: Specificity is 74.7%, meaning approximately 1 in 4 positive results may be false positives for SLE 1
- At 1:160 titer: Specificity improves to 86.2% while maintaining 95.8% sensitivity 1
- Higher titers generally indicate greater likelihood of true autoimmune disease, though this must be interpreted in clinical context 1
Why ANA Lacks Specificity
Positive ANA in Healthy Individuals
- 31.7% of healthy people test positive at 1:40 dilution 4
- 13.3% of healthy people test positive at 1:80 dilution 4
- 5.0% of healthy people test positive at 1:160 dilution 4
Other Conditions Causing Positive ANA
ANA positivity occurs in numerous non-lupus conditions, significantly reducing its specificity: 5, 6
- Other autoimmune diseases: Rheumatoid arthritis, Sjögren's syndrome, scleroderma, dermatomyositis, autoimmune hepatitis 7, 3
- Infections: Bacterial, viral, and parasitic infections can trigger positive ANA 5, 6
- Malignancies: Cancer patients may develop positive ANA 5
- Age-related: Elderly patients have higher rates of positive ANA without disease 3
Clinical Implications
Positive Predictive Value
The positive predictive value of ANA for SLE is only 11% in general hospital populations, meaning that among all positive ANA tests, only about 1 in 9 actually represents SLE. 3 This low positive predictive value reflects the test's poor specificity.
Improving Diagnostic Accuracy
To overcome the poor specificity of ANA, always order specific autoantibody testing when ANA is positive: 1, 4
- Anti-dsDNA antibodies: More specific for SLE, particularly when detected by Crithidia luciliae immunofluorescence test (CLIFT) 4
- Anti-Smith (Sm) antibodies: Highly specific for SLE 4
- Extractable nuclear antigen (ENA) panel: Helps differentiate between various autoimmune conditions 1, 4
- Pattern recognition: Different ANA patterns (homogeneous, speckled, nucleolar) suggest different antibody specificities and associated diseases 4
Critical Pitfalls
The ANA test should only be ordered when there is reasonable clinical suspicion of autoimmune disease, not as a screening test in patients with vague symptoms like fatigue alone. 2 Indiscriminate testing in low-probability populations further reduces the already poor specificity and positive predictive value. 3
Never diagnose SLE based on ANA alone—the poor specificity mandates confirmation with more specific antibodies and clinical criteria. 2, 8