Prevalence of Positive Antinuclear Antibody (ANA) Tests in the United States
The prevalence of positive Antinuclear Antibody (ANA) tests in the general United States population is approximately 20%, with most of these individuals not having or developing an autoimmune disease. 1
Understanding ANA Positivity Rates
ANA testing is widely used in clinical practice, particularly for diagnosing systemic autoimmune rheumatic diseases (SARD). However, the prevalence of positive results varies significantly based on several factors:
Population Demographics
- Gender differences: Women have higher positivity rates (10.2%) compared to men (4.6%) 2
- Age impact: Elderly patients (≥65 years) have higher rates of ANA positivity and lower test specificity 3
Test Methodology and Interpretation
- Testing method: Indirect immunofluorescence assay (IIFA) on HEp-2 cells is considered the reference method 4
- Cutoff values: An abnormal ANA should be defined as a titer above the 95th percentile of a healthy control population 4
- Screening dilution: A dilution of 1:160 is often suitable for adult populations being evaluated for SARD 4
Clinical Significance of Positive ANA Tests
Low Positive Predictive Value
- In tertiary rheumatology clinic settings, >90% of patients referred for positive ANA had no evidence of ANA-associated rheumatic disease 5
- Positive predictive value was only 11% for systemic lupus erythematosus (SLE) and 11% for other rheumatic diseases 3
- No ANA-associated rheumatic disease was identified in patients with an ANA titer <1:160 5
Associated Conditions in Non-Autoimmune Populations
In individuals without diagnosed autoimmune diseases, ANA positivity is associated with:
Increased risk of:
- Raynaud's syndrome (OR ≥2.1)
- Alveolar/perialveolar-related pneumopathies (OR ≥1.4) 1
Decreased risk of:
- Hepatitis C
- Tobacco use disorders
- Mood disorders
- Convulsions
- Fever of unknown origin
- Substance abuse disorders 1
Special Populations
- Thyroid autoimmunity: 71% of children with autoimmune thyroid diseases showed ANA positivity 6
- Metabolic abnormalities: ANA positive individuals present higher rates of metabolic abnormalities compared to control groups 2
Pitfalls in ANA Testing and Interpretation
Common Testing Errors
- Unnecessary testing in patients with low pretest probabilities (e.g., widespread pain) 5
- Failure to consider age-related increases in ANA positivity
- Misinterpretation of low titer positivity as clinically significant
Recommendations for Appropriate Testing
- Consider pretest probability before ordering ANA tests
- Report both pattern and highest dilution showing reactivity 4
- Report cytoplasmic and mitotic apparatus patterns in addition to nuclear patterns 4
- Specify the testing method used when reporting results 4
Conclusion for Clinical Practice
The high prevalence of ANA positivity in the general population (20%) necessitates careful interpretation of results. Clinicians should:
- Recognize that ANA testing is primarily intended for diagnostic purposes, not for monitoring disease progression 4
- Consider that a positive ANA test may reflect immune dysregulation that alters risk for some clinical disorders even in individuals without autoimmune disease 1
- Be aware that ANA positivity might be associated with inflammatory and immune dysfunction even in otherwise healthy individuals 2
The high prevalence of ANA positivity in the general population emphasizes the importance of clinical context when interpreting results and avoiding unnecessary referrals based solely on a positive ANA test.