Antinuclear antibodies (ANAs) are proteins made by the immune system that can attack normal tissues in the body. A positive ANA test indicates the presence of these autoantibodies, and may be associated with a variety of autoimmune diseases.
What is an ANA test?
An ANA test detects antinuclear antibodies in the blood. It’s one of the main lab tests used to help diagnose autoimmune diseases. In an ANA test, a blood sample is mixed with cells from a cell line. If ANAs are present, they will bind to structures in the cell nucleus, causing the cells to glow when viewed under a microscope.
There are two main methods of ANA testing:
- Indirect immunofluorescence assay (IFA): This is considered the gold standard method. Patient serum is added to the slide containing fixed cell substrates. If ANAs are present, they will bind to the cell contents and fluoresce when under UV light.
- Enzyme-linked immunosorbent assay (ELISA): This method detects ANAs through a color-changing chemical reaction. It’s more easily automated than IFA but may be less sensitive.
ANA tests are reported as a titer, which indicates the highest dilution of serum that still results in a positive result. For example, a titer of 1:160 means the serum sample remains positive when diluted down to 1 part serum and 160 parts diluent.
What does a positive ANA result mean?
A positive ANA indicates the presence of ANAs in the blood. However, a positive ANA alone does not confirm an autoimmune disease. That’s because:
- ANA levels can be transiently positive in healthy individuals.
- ANA positivity increases with age – up to 20% of healthy elderly individuals may test positive.
- Only specific ANA patterns are associated with certain diseases.
Based on this, a positive ANA should be followed up with additional testing. ANA patterns, titers, and additional autoantibodies can help physicians determine the likelihood of specific autoimmune diseases.
What diseases are associated with a positive ANA?
A positive ANA is associated with a number of autoimmune diseases. The most common diseases linked to ANA positivity include:
| Disease | ANA Pattern | Additional Autoantibodies |
|---|---|---|
| Systemic lupus erythematosus (SLE) | Homogeneous, speckled | Anti-dsDNA, anti-Sm, anti-Ro |
| Sjögren’s syndrome | Speckled, homogeneous | Anti-Ro, anti-La |
| Scleroderma | Centromere, speckled | Anti-Scl70, anti-centromere |
| Rheumatoid arthritis | Speckled | RF, anti-CCP |
| Polymyositis/dermatomyositis | Speckled | Anti-Jo-1 |
| Mixed connective tissue disease | Speckled | Anti-RNP |
Less commonly, diseases such as autoimmune hepatitis, primary biliary cirrhosis, and autoimmune thyroiditis may also be associated with a positive ANA.
Systemic Lupus Erythematosus (SLE)
SLE is the prototypical ANA-associated rheumatic disease. More than 95% of people with SLE have a positive ANA test result. Typical ANA patterns in SLE are homogeneous or speckled, in a diffuse pattern. SLE may also have high titers, such as 1:640 or higher.
In addition to ANA, other autoantibodies are commonly found in SLE and can help confirm the diagnosis. These include anti-dsDNA, anti-Sm, anti-Ro, anti-La, and antiphospholipid antibodies.
Sjögren’s Syndrome
Sjögren’s syndrome is an autoimmune disorder affecting the salivary and lacrimal glands. About 70% of Sjögren’s patients test positive for ANAs. The speckled ANA pattern is most closely associated with Sjögren’s.
Anti-Ro and anti-La autoantibodies are more specific to Sjögren’s syndrome. Testing for these antibodies, along with signs and symptoms of dry eyes and dry mouth, help confirm the diagnosis.
Scleroderma
Up to 80-90% of patients with scleroderma (systemic sclerosis) are ANA positive. Two patterns are most closely linked: speckled or centromere patterns. Scleroderma-specific autoantibodies provide additional diagnostic information:
- Anti-Scl70: Associated with diffuse systemic sclerosis and interstitial lung disease.
- Anti-centromere: Linked to limited cutaneous systemic sclerosis.
Rheumatoid Arthritis
About 60-80% of rheumatoid arthritis patients test positive for ANAs, typically with a speckled pattern. However, ANA testing is not very specific for RA. More specific blood tests include:
- Rheumatoid factor (RF)
- Anti-cyclic citrullinated peptide (anti-CCP)
These autoantibodies, along with joint exam findings, aid in the diagnosis of rheumatoid arthritis.
Polymyositis/Dermatomyositis
ANA positivity in polymyositis and dermatomyositis is in the range of 30-60%. The speckled pattern is most common. The anti-Jo-1 autoantibody is more specific and can help distinguish myositis from other mimicking muscle disorders.
Mixed Connective Tissue Disease
Mixed connective tissue disease (MCTD) is characterized by overlapping features of SLE, scleroderma, and polymyositis. The speckled ANA pattern and anti-RNP antibodies are closely associated with MCTD.
Other Causes of Positive ANA
While strongly associated with autoimmune disease, a positive ANA can occur due to other causes as well. These include:
- Infections: Positive ANA may transiently occur with some viral and bacterial infections. These include HIV, hepatitis, tuberculosis, and streptococcal infections.
- Medications: Certain medications like procainamide, hydralazine, quinidine, phenytoin, and minocycline can induce a positive ANA.
- Cancer: Some cancers are associated with positive ANAs, such as lung, breast, ovarian, and renal cell carcinoma.
- Family history: 20% of first-degree relatives of SLE patients may have a positive ANA without apparent disease.
- Elderly: ANA positivity increases with age and may occur in over 20% of healthy elderly individuals.
In these cases, the ANA titer is usually lower (less than 1:160), and not associated with additional autoantibodies specific for autoimmune disease.
Conclusion
A positive ANA is a sensitive screening test for autoimmune disease, but is not diagnostic on its own. Elevated titers with disease-specific ANA patterns and additional autoantibodies can help determine the likelihood of certain autoimmune diseases like SLE, Sjögren’s, scleroderma, and others.
However, a low titer ANA can also occur in healthy individuals or due to other causes. Therefore, a positive ANA requires careful correlation with a person’s full clinical presentation for accurate diagnosis and management.