Explanation

ANA screening (antinuclear antibodies): what is measured?

The test looks for antinuclear antibodies (ANA): antibodies that the body makes against parts of its own cell nucleus. Normally, the immune system makes antibodies against bacteria and viruses; in an autoimmune disease, they are also directed against the body's own tissue. The laboratory uses the standard method: immunofluorescence on HEp-2 cells, in which the antibodies light up on cultured cells under a fluorescence microscope. The result is not a number on a continuous scale but negative or a titer (how far the blood can be diluted and still light up), in practice together with the staining pattern. A higher titer means more antibodies; the pattern gives a first indication of which antibodies they may be.

What can it detect?

Systemic lupus erythematosus (SLE), an autoimmune disease that can affect the joints, skin, kidneys and other organs
Systemic sclerosis (hardening of the skin and connective tissue) and mixed connective tissue disease (a mixed picture of connective tissue diseases)
Sometimes Sjögren's syndrome (inflammation of the tear and salivary glands) and myositis (muscle inflammation); in these diseases, the ANA test is actually often negative
Autoimmune hepatitis (liver inflammation caused by the body's own immune system)

Result

What does the result mean?

Positive result

A positive ANA means that antibodies against the cell nucleus were found. On its own, this is not a diagnosis. ANA also occur in healthy people, more often as you get older, usually with a low titer; in research, more than 20 in 100 people aged 90 were positive. Infections, other autoimmune diseases and some medicines can also give a positive ANA. The result only becomes meaningful with symptoms that fit a systemic autoimmune disease; a high titer makes such a disease more likely, and the lab then usually looks further for specific antibodies (ENA and anti-dsDNA).

Negative result

A negative ANA makes SLE and systemic sclerosis unlikely, because the test is usually positive in these diseases. This does not apply to Sjögren's syndrome and myositis: in those, the ANA test is often negative while other antibodies can be detected. If the suspicion remains, a doctor may therefore still arrange further testing, for example for anti-SS-A and anti-SS-B or a myositis panel.

After an abnormal result

With a positive ANA, the laboratory usually measures specific antibodies according to the guideline: an ENA screening and, with a homogeneous or speckled pattern, anti-dsDNA. With symptoms that fit a systemic autoimmune disease, the GP refers you to a rheumatologist or internist (specialist in internal medicine). A positive ANA without matching symptoms is usually no reason for referral; sometimes a doctor chooses to monitor the symptoms over time.

Reliability

How reliable is the test?

The ANA test is sensitive but not very specific: in most people with SLE the result is positive, but a positive result also occurs without an autoimmune disease. According to the performing laboratory, the greatest value therefore lies in the negative result, which makes an autoimmune disease such as SLE or systemic sclerosis unlikely; a positive result is mainly the starting point for testing for specific antibodies (ENA). According to the CMI/NVKC guideline and a review article in the Dutch Journal of Medicine (NTvG), the test only has value if there is a clear clinical suspicion of a systemic autoimmune disease. The Dutch Society for Rheumatology has included 'only request an ANA test for the right reasons' in its Choosing Wisely recommendations. An ANA test with the question of 'whether something autoimmune is going on' mainly produces results that do not fit the picture.

What can affect the result?

ANA occur in healthy people and more often at older ages, usually with a low titer.
Some medicines (including hydralazine and procainamide), infections such as tuberculosis and other diseases can give a positive ANA.
This test uses the HEp-2 method recommended by the guideline; a screening with a mixture of fixed antigens (ENA screen) finds fewer antibodies and, according to the guideline, is not a replacement for the ANA test.
Titers depend on the cells, equipment and cut-off value used; results from different laboratories cannot simply be compared.

Who it is for

Who is the test useful for?

Useful for

Useful if several symptoms together fit a systemic autoimmune disease: inflamed joints with a skin rash (especially after sunlight), white or blue fingers in the cold, unexplained fever, inflammation of the lining of the lungs or heart, or protein in the urine. With only tiredness or joint pain without other signs, the chance that the result clarifies anything is small. Specialists advise against using the test as a general check for autoimmune diseases in people without symptoms.

How common is it?

The diseases the ANA test is intended for, such as SLE and systemic sclerosis, are rare. A positive ANA is much more common than those diseases: of the people tested from general practice, 6 in 100 had a positive ANA, and of those only about 3 in 10 had a high, clinically more relevant titer. In older people, the number of positive results without disease increases further.

NTvG (2021) and the CMI/NVKC guideline on ANA/ENA

Drawbacks and risks

A positive ANA without symptoms is common and can lead to worry, repeated tests and referrals without any disease being found.
A negative result does not rule out Sjögren's syndrome and myositis and can therefore give false reassurance.

Get tested