What is antinuclear antibody

Antinuclear antibodies (ANA) are a group of antibodies produced by your immune system when it fails to adequately distinguish between “self” and “nonself.” These antibodies, known as autoantibodies, attack your own healthy cells and cause signs and symptoms such as tissue and organ inflammation, joint and muscle pain, and fatigue. Antibodies are proteins that your immune system – white blood cells (B cells) – makes to recognize and fight foreign substances like viruses and bacteria. When an antibody recognizes the foreign proteins of an infectious organism, it recruits other proteins and cells to fight off the infection. This cascade of attack is called inflammation. Sometimes these antibodies make a mistake, identifying normal, naturally-occurring proteins in our bodies as being “foreign” and dangerous. When these antibodies make incorrect calls, identifying a naturally-occurring protein (or self protein) as foreign, they are called autoantibodies. But the antinuclear antibodies (ANA) specifically target substances found in the nucleus of a cell, hence the name “antinuclear.” The antinuclear antibody ANA test identifies the presence of these autoantibodies in your blood. Autoantibodies start the cascade of inflammation, causing the body to attack itself.

The presence of large amount of ANA antinuclear antibody may be a marker of an autoimmune process and is associated with several autoimmune disorders but is most commonly seen with the autoimmune disorder systemic lupus erythematosus (SLE). Antinuclear antibodies (ANA) could also mean other autoimmune diseases, including lupus, scleroderma, Sjögren’s syndrome, polymyositis/dermatomyositis, mixed connective tissue disease, drug-induced lupus, and autoimmune hepatitis. A positive antinuclear antibody (ANA) can also be seen in juvenile arthritis. Other conditions, such as cancer, can cause a positive ANA.

Some medications can cause a positive antinuclear antibody (ANA). It is important to talk with your doctor about all the drugs you are taking – prescription, over-the-counter, and street.

The ANA antinuclear antibody test is one of the primary tests for helping to diagnose a suspected autoimmune disorder or ruling out other conditions with similar signs and symptoms. As such, antinuclear antibody test is often followed by other tests for autoantibodies that may help to establish a diagnosis. These may include, for example, an ENA (extractable nuclear antibody) panel, anti-dsDNA, anti-centromere and/or anti-histone test.

The positive antinuclear antibody (ANA) reading simply tells your doctor to keep looking. In fact, you may have a positive ANA without any disease process which means that the evidence is not there to make a diagnosis of lupus or any other autoimmune disease. To make a definite diagnosis, your doctor will need more blood tests along with history of your symptoms and a physical examination.

Antinuclear antibody (ANA) key points

• Antinuclear antibody (ANA) is a highly sensitive test for the diagnosis of SLE, being positive in >95% of patients. The specificity of ANA is, however, low.
• Antinuclear antibody (ANA) is also positive in up to 70% of other systemic rheumatic conditions, often at high titer.
• Antinuclear antibody (ANA) may also be positive, usually in low titer, in other inflammatory and neoplastic diseases and in a proportion of the normal population, with the prevalence increasing with age.
• Higher antinuclear antibody (ANA) titers usually have greater diagnostic significance, particularly in younger patients.
• Use of the antinuclear antibody (ANA) by itself as a screening test should be avoided, as interpretation is difficult in the absence of features suggestive of a systemic rheumatic disease.
• Antinuclear antibody (ANA) titers often remain elevated in remission and do not reflect disease activity.
• Antinuclear antibody (ANA) patterns have limited correlation with specific syndromes, e.g., anticentromere antibodies are characteristic of the CREST syndrome (limited scleroderma); rim pattern suggests SLE. DFS70 pattern may indicate less likelihood of systemic rheumatic disease.
• Specificity of the antibody for antigenic determinants is established by other tests, for example, an ENA (extractable nuclear antibody) panel, anti-dsDNA, anti-centromere and/or anti-histone test.

What is antinuclear antibody test

The antinuclear antibody (ANA) test is used as a primary test to help evaluate a person for autoimmune disorders that affect many tissues and organs throughout the body (systemic) and is most often used as one of the tests to help diagnose systemic lupus erythematosus (SLE).

ANA are a group of autoantibodies produced by a person’s immune system when it fails to adequately distinguish between “self” and “nonself.” They target substances found in the nucleus of a cell and cause organ and tissue damage.

Depending on a person’s signs and symptoms and the suspected disorder, ANA testing may be used along with or followed by other autoantibody tests. Some of these tests are considered subsets of the general ANA test and detect the presence of autoantibodies that target specific substances within cell nuclei, including anti-dsDNA, anti-centromere, anti-nucleolar, anti-histone and anti-RNA antibodies. An ENA panel may also be used in follow up to an ANA.

These supplemental tests are used in conjunction with a person’s clinical history to help diagnose or rule out other autoimmune disorders, such as Sjögren syndrome, polymyositis and scleroderma.

Different laboratories may use different test methods to detect ANA. Two common methods include immunoassay and indirect fluorescent antibody (IFA). IFA is considered the gold standard. Some laboratories will use immunoassay to screen for ANA and use IFA to confirm positive or equivocal results.

• Indirect fluorescent antibody (IFA)—this is a method in which a person’s blood sample is mixed with cells that are affixed to a slide. Autoantibodies that may be present in the blood react with the cells. The slide is treated with a fluorescent antibody reagent and examined under a microscope. The presence (or absence) and pattern of fluorescence is noted. The results of indirect fluorescent antibody (IFA) are reported as a titer. Titers are expressed as ratios. For example, the result 1:320 means that one part blood sample was mixed with 320 parts of a diluting substance and ANA was still detectable.
• Immunoassays (enzyme linked immunosorbent assay, ELISA, or enzyme immunoassay, EIA) –these methods are usually performed on automated instrumentation but may be less sensitive than IFA in detecting ANA. The results are usually reported as a number with an arbitrary unit of measure (abbreviated as a “U” on the report, for example).

Other laboratory tests associated with the presence of inflammation, such as erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP), may also be used to evaluate a person for SLE or other autoimmune disease.

What happens during an antinuclear antibody (ANA) test?

A health care professional will take a blood sample from a vein in your arm, using a small needle. After the needle is inserted, a small amount of blood will be collected into a test tube or vial. You may feel a little sting when the needle goes in or out. This usually takes less than five minutes.

Will I need to do anything to prepare for the antinuclear antibody (ANA) test?

An antinuclear antibody (ANA) test requires a sample of your blood. If your sample is being used only for an antinuclear antibody (ANA) test, you can eat and drink normally before the test. If your blood sample will be used for additional tests, you might need to fast for a time before the test. Your doctor will give you instructions.

Certain drugs affect the accuracy of the test, so bring your doctor a list of the medications you take.

When is antinuclear antibody (ANA) test ordered?

The antinuclear antibody (ANA) test is ordered when someone shows signs and symptoms that are associated with a systemic autoimmune disorder. People with autoimmune disorders can have a variety of symptoms that are vague and non-specific and that change over time, progressively worsen, or alternate between periods of flare ups and remissions.

An antinuclear antibody (ANA)test is used to help diagnose autoimmune disorders, including:

• Systemic lupus erythematosus (SLE). This is the most common type of lupus, a chronic disease affecting multiple parts of the body, including the joints, blood vessels, kidneys, and brain.
• Rheumatoid arthritis, a condition that causes pain and swelling of the joints, mostly in the hands and feet
• Scleroderma, a rare disease affecting the skin, joints, and blood vessels
• Sjogren’s syndrome, a rare disease affecting the body’s moisture-making glands

Some examples of signs and symptoms of systemic autoimmune disorder include:

• Low-grade fever
• Persistent fatigue, weakness
• Arthritis-like pain in one or more joints
• Red rash (for lupus, one resembling a butterfly across the nose and cheeks)
• Skin sensitivity to light
• Hair loss
• Muscle pain
• Numbness or tingling in the hands or feet
• Inflammation and damage to organs and tissues, including the kidneys, lungs, heart, lining of the heart, central nervous system, and blood vessels.

Normal antinuclear antibody (ANA) results

Some normal people have a low level of antinuclear antibody (ANA). Thus, the presence of a low level of ANA is not always abnormal.

ANA is reported as a “titer”. Low titers are in the range of 1:40 to 1:60. A positive antinuclear antibody (ANA) test is of much more importance if you also have antibodies against the double-stranded form of DNA.

The presence of antinuclear antibody (ANA) does not confirm a diagnosis of systemic lupus erythematosus (SLE). However, a lack of antinuclear antibody (ANA) makes that diagnosis much less likely.

Although antinuclear antibody (ANA) are most often identified with SLE, a positive antinuclear antibody (ANA) test can also be a sign of other autoimmune diseases.

Normal value ranges may vary slightly among different laboratories. Talk to your provider about the meaning of your specific test results.

The examples above show the common measurements for results for these tests. Some laboratories use different measurements or may test different specimens.

Further tests can be run on blood with a positive antinuclear antibody (ANA) test to get more information.

What does positive ANA antinuclear antibody mean?

A positive antinuclear antibody (ANA) test result means that autoantibodies are present. In a person with signs and symptoms, this suggests the presence of an autoimmune disease, but further evaluation is required to assist in making a final diagnosis.

Patterns of cellular fluorescence

In addition to a titer, positive results on indirect fluorescent antibody (IFA) will include a description of the particular type of fluorescent pattern seen. Different patterns have been associated with different autoimmune disorders, although some overlap may occur. Some of the more common patterns include:

• Homogenous (diffuse) ANA — associated with SLE, mixed connective tissue disease, and drug-induced lupus
• Speckled ANA — associated with SLE, Sjögren syndrome, scleroderma, polymyositis, rheumatoid arthritis, and mixed connective tissue disease
• Nucleolar ANA — associated with scleroderma and polymyositis
• Centromere pattern (peripheral) ANA — associated with scleroderma and CREST (Calcinosis, Raynaud syndrome, Esophogeal dysmotility, Sclerodactyly, Telangiectasia)

A positive result from the enzyme linked immunosorbent assay (ELISA) or enzyme immunoassay (EIA) method will be a number of units that is above the laboratory’s reference number (cutoff) for the lowest possible value that is considered positive.

An example of a positive result using the IFA method would give the dilution titer and a description of the pattern, such as “Positive at 1:320 dilution with a homogenous pattern.”

For either method, the higher the value reported, the more likely the result is a true positive.

Antinuclear antibody (ANA) test results can be positive in people without any known autoimmune disease and thus need to be evaluated carefully in conjunction with an individual’s signs and symptoms.

An antinuclear antibody (ANA) test may become positive before signs and symptoms of an autoimmune disease develop, so it may take time to tell the meaning of a positive ANA in a person who does not have symptoms.

Conditions associated with a positive ANA test

About 3-5% of healthy Caucasians may be positive for antinuclear antibody (ANA), and it may reach as high as 10-37% in healthy individuals over the age of 65 because antinuclear antibody (ANA) frequency increases with age. These would be considered false-positive results because they are not associated with an autoimmune disease. Such instances are more common in women than men.

The most common condition is SLE.

SLE (systemic lupus erythematosus) — antinuclear antibody (ANA) are most commonly seen with SLE. About 95% of those with SLE have a positive ANA test result. If someone also has symptoms of SLE, such as arthritis, a rash, and skin sensitivity to light, then the person probably has SLE. A positive anti-dsDNA and anti-SM (often ordered as part of an ENA panel) help confirm that the condition is SLE.

Other conditions in which a positive ANA test result may be seen include:

Drug-induced lupus — a number of medications may trigger this condition, which is associated with SLE symptoms. When the drugs are stopped, the symptoms usually go away. Although many medications have been reported to cause drug-induced lupus, those most closely associated with this syndrome include hydralazine, isoniazid, procainamide, and several anticonvulsants. Because this condition is associated with the development of autoantibodies to histones, an anti-histone antibody test may be ordered to support the diagnosis.

Sjögren syndrome — 40-70% of those with this condition have a positive ANA test result. While this finding supports the diagnosis, a negative result does not rule it out. A health practitioner may want to test for two subsets of ANA: Anti-SS-A (Ro) and Anti-SS-B (La). About 90% or more of people with Sjögren syndrome have autoantibodies to SSA.

Scleroderma (systemic sclerosis) —About 60-90% of those with scleroderma have a positive ANA. In people who may have this condition, ANA subset tests can help distinguish two forms of the disease, limited versus diffuse. The diffuse form is more severe. The limited form is most closely associated with the anticentromere pattern of ANA staining (and the anticentromere test), while the diffuse form is associated with autoantibodies to Scl-70.

Less commonly, antinuclear antibody (ANA) may occur in people with Raynaud syndrome, arthritis, dermatomyositis or polymyositis, mixed connective tissue disease, and other autoimmune conditions.

The presence of antinuclear antibody (ANA) in the blood may be due to several other disorders besides SLE. These include:

• Chronic liver disease
• Collagen vascular disease
• Drug-induced lupus erythematosus
• Myositis (inflammatory muscle disease)
• Rheumatoid arthritis
• Sjögren syndrome
• Systemic sclerosis (scleroderma)
• Thyroid disease

A health practitioner must rely on test results, clinical symptoms, and the person’s history for diagnosis. Because symptoms may come and go, it may take months or years to show a pattern that might suggest SLE or any of the other autoimmune diseases.

A negative ANA result makes SLE an unlikely diagnosis. It usually is not necessary to immediately repeat a negative ANA test; however, due to the episodic nature of autoimmune diseases, it may be worthwhile to repeat the ANA test at a future date if symptoms recur.

Aside from rare cases, further autoantibody (subset) testing is not necessary if a person has a negative antinuclear antibody (ANA) test result.

Antinuclear antibody (ANA) testing is not used to track or monitor the clinical course of SLE, thus serial antinuclear antibody (ANA) tests for diagnosed patients are not commonly ordered.

Use of a number of drugs, some infections, autoimmune hepatitis and primary biliary cirrhosis as well as other conditions mentioned above can give a positive result for the antinuclear antibody (ANA) test.

Is SLE the same thing as lupus?

There are actually several forms of lupus. SLE is the form that is most commonly referred to when someone mentions “lupus.” Systemic lupus means that almost any organ or system in your body can be affected. This is the most severe form. There are other forms of lupus that are primarily limited to skin, such as discoid and subacute cutaneous lupus. Symptoms include rashes that may be found in many shapes and locations on the body. A butterfly-shaped rash is commonly seen on or near the face.

How should I handle a positive antinuclear antibody (ANA) test?

Your doctor or rheumatologist will interpret your antinuclear antibody (ANA) in the context of other laboratory studies and your clinical history, including family history. Remember, a single positive ANA does not imply autoimmune disease, nor does a positive ANA require immediate treatment. Lab levels vary; some autoantibodies are normal and this result may not indicate a problem.

Your rheumatologist will determine what happens next based on additional exploration. By working with your doctor and asking questions you will get the best care for your particular situation. Keep in mind, even if your antinuclear antibody (ANA) reading does lead to an autoimmune diagnosis, there are treatments for autoimmune diseases.

My doctor told me my antinuclear antibody (ANA) test is positive, but he isn’t sure if I have lupus. How can this be?

A positive antinuclear antibody (ANA) result means that you have a higher than normal concentration of these antibodies. This is one of the tools in diagnosing lupus as well as several other autoimmune diseases, so a positive result may be related to lupus or to another disease. Or you may simply have a higher than normal concentration of these autoantibodies that may not have any impact on your health. Even among people with lupus, ANA results can vary widely; one person can be in remission at a certain titer of ANA while another can be extremely ill at the same titer. Autoimmune diseases often have a systemic effect on the body and are very complex by nature. Your healthcare provider will interpret what the test results mean for you and may need to compare your test results as well as the severity of your symptoms over a period of time in order to make a definitive diagnosis. This additional time may also allow your healthcare provider to eliminate other possible causes of your symptoms. Another diagnostic tool is to perform additional testing for the autoantibodies Smith and ds-DNA, which, if positive, would confirm SLE.