The antinuclear antibody (ANA) test is a common screening tool used to detect autoimmune diseases. It works by detecting antibodies called antinuclear antibodies in the blood that can attack the body’s own tissues and cause autoimmune diseases like lupus, rheumatoid arthritis, Sjögren’s syndrome, and others.
What is the ANA test?
The ANA test detects antinuclear antibodies (ANA) in the blood. ANAs are substances produced by the immune system that attack the body’s own tissues, causing inflammation and potentially leading to autoimmune disease.
In the ANA test, a person’s serum is added to human cells in a culture. If ANAs are present, they will bind to structures inside the nuclei of the cells. A fluorescent dye is added, which causes ANAs bound to the cells to glow when viewed under a special microscope. The pattern and brightness of the fluorescence signal whether and what levels of ANAs are present.
There are two possible results from an ANA test:
- Negative – No ANAs detected. This is considered a normal result.
- Positive – ANAs are present at abnormally high levels. This indicates an increased likelihood of having an autoimmune disorder.
If the test is positive, the pattern of fluorescence may indicate the type of autoantibodies present. For example, a homogenous pattern is associated with systemic lupus erythematosus (SLE), while a speckled pattern is linked to Sjögren’s syndrome.
Why is the ANA test done?
The ANA test is commonly ordered when a person presents symptoms that may be suggestive of an underlying autoimmune disease. This includes:
- Joint pain, swelling, and stiffness
- Skin rashes and photosensitivity
- Fatigue and weakness
- Fever
- Dry eyes and mouth
- Numbness and tingling in the extremities
- Hair loss
- Raynaud’s phenomenon (fingers turning white or blue in the cold)
However, these non-specific symptoms can also be caused by other conditions. There are no symptoms that are diagnostic for autoimmune diseases on their own. Therefore, the ANA test is used as an initial screening tool to determine if autoantibodies may be present and further specific autoimmune testing is warranted.
Who should get tested?
The ANA test is primarily ordered for patients presenting symptoms that may indicate an underlying autoimmune condition. However, it is important to note that a positive ANA test alone is not sufficient to diagnose an autoimmune disease.
Guidelines for ANA testing from the American College of Rheumatology recommend the test for patients with:
- Unexplained signs and symptoms suggestive of systemic autoimmune disease lasting >1 week
- Unexplained signs and symptoms of >3 organ systems lasting >6 weeks
- Biopsy-proven lupus nephritis or other autoimmune rheumatic diseases
ANA testing is not recommended for general screening in asymptomatic patients or as a stand-alone diagnostic test.
Can ANA test results change over time?
Yes, ANA test results can fluctuate over time. There are a few key reasons why ANA levels may vary:
1. Infections
Temporary elevations in ANA levels can occur during both viral and bacterial infections. This is thought to be due to increased immune system activity against the infection producing excess autoantibodies. Often ANA levels will return to normal after the infection resolves.
2. Medications
Certain prescription medications are associated with drug-induced lupus, an autoimmune reaction that causes symptoms similar to SLE. Medications that can trigger drug-induced lupus and increase ANA levels include:
- Hydralazine (blood pressure medication)
- Procainamide (heart arrhythmia medication)
- Isoniazid (antibiotic for tuberculosis)
- Methyldopa (blood pressure medication)
- Chlorpromazine (antipsychotic medication)
- Anti-seizure medications
In most cases, ANA levels return to normal after discontinuing the culprit medication. But sometimes drug-induced lupus can persist even after stopping the medication.
3. Autoimmune flares and remission
In established autoimmune diseases like lupus and rheumatoid arthritis, ANA levels may rise and fall with disease activity. During flares when the disease is active, ANA levels usually increase. They tend to decrease again when the flare resolves and the disease enters a quiet period of remission.
4. Pregnancy
ANA levels can rise during pregnancy and typically fall again after giving birth. This is thought to be related to normal immune system changes that occur during pregnancy.
Elevated ANA levels alone without other clinical signs of autoimmune disease are usually not a cause for concern or a reason to test the fetus. But in mothers who already have an autoimmune condition like lupus, rises in ANA may indicate a disease flare.
5. Aging
ANA levels tend to increase slightly with older age even in healthy adults. Rates of autoantibody positivity have been found to increase by about 1% per year of age. However, significant elevations should still warrant investigation for underlying autoimmune disease.
Mild increases in ANA levels in otherwise healthy older individuals are usually not clinically significant. But in context of symptoms, ANA levels that are clearly abnormal for the patient’s age could indicate an autoimmune condition.
ANA titer levels
ANA test results are reported as a titer, which is a measurement of the concentration of antibodies in the blood sample. The titer represents how much the blood sample needs to be diluted before the antibodies are no longer detectable under the microscope.
ANA titers are reported on a scale from 1:40 to 1:5120 or higher. Low positive titers between 1:40 and 1:80 have less association with autoimmune disease than high positive titers ≥1:160.
Here is an overview of what different ANA titer ranges indicate:
| ANA Titer | Interpretation |
|---|---|
| <1:40 | Negative |
| 1:40 – 1:80 | Low positive |
| >1:160 | High positive |
While high positive ANA titers have a stronger association with autoimmune diseases, low positive results can also warrant further evaluation in the right clinical context.
What does it mean if my ANA test changed from negative to positive?
A change from a negative to a positive ANA test result indicates that autoantibodies are now detectable in your blood when they previously were not. This could be due to:
- The onset or progression of an autoimmune disease
- A temporary increase in antibodies from an infection or medication
- Increasing antibodies due to pregnancy
- A mild increase due to aging
- Test variability between different labs and methods
A newly positive ANA is reason for further investigation but is not diagnostic on its own. Your doctor will consider the titer level, your symptoms, and other factors to determine if specific autoimmune disease testing and treatment may be warranted.
What does it mean if my ANA titer level increased?
An increase in your ANA titer indicates a rise in the concentration of antinuclear antibodies in your blood. Reasons for titer increases include:
- Progression of an existing autoimmune disease, signaling a flare
- Development of a new autoimmune disease
- A temporary spike from an infection, medication, or pregnancy
ANA levels can also increase due to variability between testing laboratories. Always compare results from the same lab. Significant titer increases, especially multiple times the upper limit of normal, warrant medical evaluation to determine if there are any symptoms or signs of an underlying autoimmune disorder.
What does it mean if my ANA changed from positive to negative?
A change from a positive to a negative ANA result means antinuclear antibodies are no longer detectable in your blood sample. Possible reasons include:
- Your autoimmune disease is well-controlled in remission
- Your prior positive result was falsely positive or reflected a transient increase from an infection, medication, or pregnancy
- You are responding well to immunosuppressant treatment
- Variability between laboratories affected the results
A negative result is reassuring and may reflect disease remission. However, some autoimmune diseases like lupus are known to have fluctuating ANA levels that vary with disease activity. Your doctor will interpret your result in context with your symptoms, treatment history, and other lab tests.
What does it mean if my ANA titer decreased?
A decrease in your ANA titer signals a reduction in the concentration of antinuclear antibodies compared to your prior test. This may reflect:
- Successful treatment of your autoimmune condition
- Entering remission of an autoimmune flare
- Resolution of a temporary antibody increase from an infection, medication, or pregnancy
- Variability between testing laboratories
An ANA titer decrease is usually a good sign, but must be interpreted carefully by your doctor along with your full clinical picture. Some patients have persistent autoimmune disease despite drops in ANA levels.
My ANA changed, but my symptoms are the same. What does this mean?
It is possible for your ANA test result to change while your symptoms remain stable. Reasons may include:
- Transient ANA increase – A temporary rise from an infection or medication exposure can cause a positive ANA in someone with no autoimmune issues.
- Mild titer variability – Small titer fluctuations within the same range are not considered significant changes.
- Lab differences – Different testing methods and cutoff values can affect results.
- Early stages of autoimmunity – ANA levels may start increasing before onset of symptoms.
- Remission of autoimmunity – ANA levels may decrease while residual symptoms persist.
The pattern of symptoms over time is most important. Stable symptoms with changing ANA levels may warrant repeat testing to assess trends. However, symptoms always take priority over lab tests alone.
My ANA changed, and I have new symptoms. What should I do?
If your ANA test changed from negative to positive or shows a significant titer increase in tandem with new or worsening symptoms, this warrants prompt medical evaluation. Important symptoms to report to your doctor include:
- Joint pain or swelling
- Rash or skin changes
- Prolonged fever
- Vision problems
- Shortness of breath
- Chest pain
- Neurological symptoms like numbness or headaches
- Blood in the urine
- Unexplained weight loss
Your doctor will likely order more specific autoantibody tests, imaging, or a biopsy to look for evidence of systemic autoimmune disease affecting organs like the kidneys, skin, joints, or nervous system. Prompt treatment can help prevent complications from uncontrolled autoimmune disease.
Key takeaways
- ANA test results can temporarily increase due to infections, medications, pregnancy, and aging.
- In existing autoimmune diseases, ANA levels often rise and fall with disease activity and flares.
- ANA should not be used as a stand-alone test but interpreted in context of a person’s symptoms and clinical history.
- Significant ANA changes, especially with new symptoms, warrant medical evaluation for autoimmune conditions.
- Always compare ANA tests done by the same laboratory, since ranges vary.
The bottom line
ANA test results can vary over an individual’s lifetime for many reasons. Changing ANA levels may reflect the progression or control of an underlying autoimmune disorder. However, mild fluctuations may not be clinically meaningful, especially without correlated symptoms. Doctors must interpret ANA trends carefully in the full clinical context to guide screening and treatment for autoimmune diseases appropriately.