Explanation

ENA (antibodies against extractable nuclear antigens): what is measured?

ENA are proteins from the cell nucleus that can be extracted in the laboratory. The test looks for autoantibodies (antibodies against the body's own tissue) against a fixed set of these proteins, including SS-A (Ro), SS-B (La), Sm, U1RNP, Scl-70, CENP-B and Jo-1. This is a screening test: the laboratory tests the blood with a fluorescence enzyme immunoassay (FEIA) against a mixture of these proteins at once, and you get one result, positive or negative. So the screening does not say which protein the antibodies are directed against; after a positive result, a separate test of the individual antibodies is needed for that.

What can it detect?

Sjögren's syndrome (inflammation of the tear and salivary glands), usually with anti-SS-A and sometimes anti-SS-B
Systemic lupus erythematosus (SLE), including with anti-Sm
Systemic sclerosis (anti-Scl-70 or anti-CENP-B) and mixed connective tissue disease (anti-U1RNP)
Myositis (muscle inflammation), including with anti-Jo-1

Result

What does the result mean?

Positive result

A positive result means antibodies against one or more nuclear proteins were found. Which antibody it is only becomes clear from a separate test of the individual antibodies; with fitting symptoms, this can support a particular diagnosis. It is not a diagnosis in itself: autoantibodies also occur in healthy people, more often at older ages, and with the use of some medicines. A weakly positive screening without symptoms has little meaning.

Negative result

A negative result makes a number of autoimmune diseases less likely, for example Sjögren's syndrome with anti-SS-A. The test does not rule them out: a small share of people with an autoimmune disease make no detectable antibodies, and antibodies against proteins that are not in the panel are not found. If the suspicion remains, the guideline advises doing an ANA test (HEp-2) after all or repeating the test later.

After an abnormal result

After a positive screening, the individual antibodies are tested to see which protein they are directed against. With a positive result and fitting symptoms, the GP usually refers to a rheumatologist or internist, who assesses the result together with a physical examination and other blood tests. A positive result without symptoms usually does not lead to treatment; new symptoms are, however, a reason to have things assessed again.

Reliability

How reliable is the test?

According to the CMI/NVKC guideline, an ENA test belongs in the pathway after a positive ANA test or with a clear suspicion of an autoimmune disease associated with these antibodies; a positive screening is followed by typing of at least eight standard antibodies. An ENA screening does not replace the ANA test, because it only contains a fixed set of proteins. If Sjögren's syndrome is suspected, direct testing for anti-SS-A and anti-SS-B is useful, even if the ANA test is negative. The result can only be interpreted together with symptoms and a physical examination.

What can affect the result?

This screening with a mixture of proteins does not say which antibody is present; that requires a separate test of the individual antibodies.
Autoantibodies are also found in people without an autoimmune disease, especially in older people and with the use of some medicines.
The test method and cut-off value differ by laboratory; a weakly positive result is hard to interpret.
Antibodies against nuclear proteins that are not in the panel are missed.

Who it is for

Who is the test useful for?

Useful for

Useful after a positive ANA test, or with symptoms that clearly fit one of these diseases: dry eyes and a dry mouth with joint symptoms, a skin rash with joint inflammation, tight or thickened skin of the fingers with white fingers in the cold, or muscle weakness. Without such symptoms, for example with only tiredness or muscle pain, the chance of an unclear or false-positive result is greater than the chance of a meaningful finding.

How common is it?

The diseases associated with these antibodies, such as Sjögren's syndrome, SLE and systemic sclerosis, are rare. Autoantibodies themselves are much more common: according to the Dutch Society for Clinical Chemistry (NVKC), in healthy people over 65 the share of positive results without an autoimmune disease can rise to almost 40 in 100. Dutch figures per individual antibody are not available.

NVKC (allesovertesten.nl) and the CMI/NVKC guideline on ANA/ENA

Drawbacks and risks

A positive result without fitting symptoms can cause unnecessary worry and follow-up tests.
A negative result does not rule out an autoimmune disease.

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