ANA (antinuclear antibodies)

What is being analysed?
The ANA test detects antinuclear antibodies (ANA) in the blood. In some situations the immune system goes wrong and reacts against the body’s own cells or tissues instead of against external agents. This process is mediated by molecules called autoantibodies, produced by an immune system that normally defends the body against invading bacteria or viruses. When this happens, the resulting disease is called autoimmune (autoimmunity means immunity against the body’s own “self”). A positive ANA is an indicator of an autoimmune process and is associated with most autoimmune diseases, mainly SLE.

How is it used?
When is it requested?
What does the test result mean?
Is there anything else I should know?

How is it used?
The test is used in the diagnosis of systemic lupus erythematosus (SLE) and drug-induced lupus, and can be positive in scleroderma, Sjögren’s syndrome, Raynaud’s disease, juvenile chronic arthritis, rheumatoid arthritis, antiphospholipid syndrome, autoimmune hepatitis and many other diseases, autoimmune or not. For this reason a correct diagnosis of SLE can be difficult. Since ANA can also be positive in other diseases, further tests can help in diagnosing SLE. Naturally these tests must also be used together with the patient’s symptoms and medical history to rule out other autoimmune diseases.

When is it requested?
Since the diagnosis of autoimmune diseases can be complex, this test is a first step in identifying SLE and other autoimmune disorders with a complex set of symptoms. Symptoms such as joint pain and swelling, unexplained fever, fatigue and skin rashes can come and go and be moderate or severe. It can also take months or years before a typical picture of SLE or another autoimmune disease develops.

What does the test result mean?
A positive test may suggest an autoimmune disease, but specific tests are needed to make a definitive diagnosis. ANA can also be positive without an autoimmune disease. Although this is not common, false positives become more frequent with age.

About 95% of patients with SLE have a positive ANA test. If a patient has symptoms typical of SLE, such as arthritis, a rash or autoimmune thrombocytopenia (a low platelet count), they probably have SLE. In these cases a positive ANA can help make the diagnosis. If needed, two further tests, anti-dsDNA and anti-Sm antibodies, can identify SLE. A positive anti-dsDNA strengthens the diagnosis of SLE, and high anti-Sm levels are even more specific for SLE.

A positive ANA can also point to drug-induced lupus. This condition is associated with the development of autoantibodies against histones, nuclear proteins that wrap and protect DNA. A positive anti-histone antibody test can support a diagnosis of drug-induced lupus.

Other conditions in which the ANA test can be positive include:

• Sjögren’s syndrome: 40 to 70% of patients with this disease have a positive ANA. While this result supports the diagnosis, it is not essential. There are two further tests: antibodies to the SSA and SSB ribonucleoproteins. Anti-SSA autoantibodies can be found in 90% or more of patients with Sjögren’s when enzyme immunoassay is used.
• Scleroderma: 60 to 90% of patients with scleroderma have a positive ANA. In these patients further tests can help distinguish the limited form from the diffuse form, which is the more serious. The limited form is associated with anti-centromere antibodies, while the diffuse form is associated with anti-Scl-70 autoantibodies.
• A positive ANA can also be found in people with Raynaud’s disease, juvenile chronic arthritis or antiphospholipid syndrome, but the diagnosis must be confirmed on the basis of the person’s symptoms and medical history.

If the ANA test is negative, a diagnosis of SLE is unlikely. Unless an error in performing the test is suspected, there is no need to repeat it straight away. However, as autoimmune diseases develop over time, it may need to be repeated in the future.

Except in rare cases, there is no need to test for autoantibody subtypes in patients with a negative ANA.

Is there anything else I should know?
There are specific autoantibody subtypes that can reliably indicate certain autoimmune diseases; these include anti-dsDNA, anti-Sm, antibodies to the Sjögren’s syndrome antigens (SSA, SSB), Scl-70 antibodies, anti-centromere, anti-histone and anti-RNP antibodies.

Some medicines and infections, as well as the other conditions mentioned above, can cause false positive results. These medicines can cause a condition called drug-induced lupus, with symptoms similar to those of SLE. When the medicine is stopped, the symptoms usually go away. Although many medicines can cause this condition, those most closely associated with it are hydralazine, isoniazid, procainamide and some antiepileptics.

1. Why are they called “antinuclear” antibodies?
2. If the ANA test is negative, why should other antibody tests be done?
3. How can a patient have a positive ANA without it being certain that they have lupus?
4. Are SLE and lupus the same disease?

1. Why are they called “antinuclear” antibodies?
ANA are gamma globulins (antibodies) found in patients with some autoimmune diseases. They are directed against components of the cell nucleus.

2. If the ANA test is negative, why should other antibody tests be done?
Antibody subtypes are almost never positive in people who are ANA negative. These tests should generally not be requested in patients who are not ANA positive.

3. How can a patient have a positive ANA without it being certain that they have lupus?

The immune system normally produces antibodies in response to disease and infection. In autoimmune diseases this system malfunctions and produces autoantibodies, i.e. antibodies directed against the body’s own (“self”) tissues.

ANA are antibodies directed against the cell nucleus or against parts of the cell’s control machinery. The ANA test is based on measuring their level in the blood: a result is positive when the level is above normal. This test is one of the tools used to diagnose SLE and other autoimmune conditions, since positive results can be found both in lupus and in other diseases. A positive result can also occur in healthy people, just as one person can naturally have a slightly higher body temperature than another. Even among people with lupus, results can vary widely: for example, one person with a certain antibody titre may be in remission, while another with the same titre may have active disease. The results must in any case be interpreted only by a doctor, who, before making a definite diagnosis, may need to compare the results of several tests over time, also looking for a correlation with the severity of the disease. In this way other diseases with the same symptoms can be ruled out.

4. Are SLE and lupus the same disease?
There are several forms of lupus. When people talk about “lupus” they usually mean SLE. It is called systemic when the disease involves several organs, and this is the form with the most serious effects on the body. There are also forms of lupus that affect only the skin, with rashes whose location and intensity vary from person to person; the symptoms of lupus are in fact very varied. There is also a condition called drug-induced lupus, which appears in some people after taking certain medicines. The symptoms usually go away after the medicine is stopped. This form affects only a small percentage of people taking these medicines.