ANTINUCLEAR ANTIBODIES OVERVIEW
A healthcare provider may request that a patient have a test for antinuclear antibodies (ANA) as part of an evaluation for possible autoimmune disease. Antibodies are proteins that are made as part of an immune response. Normally, the immune system responds to an infection by producing large numbers of antibodies to fight bacteria or viruses. However, when a person has an autoimmune disease, the immune system malfunctions and may produce large amounts of potentially harmful antibodies directed against one’s own body. These self-directed antibodies are referred to as autoantibodies. Autoantibody-mediated inflammation and cell destruction may affect blood cells, skin, joints, kidneys, lungs, nervous system, and other organs of the body.
The ANA test identifies autoantibodies that target substances contained inside cells. Although the name implies that the test detects only autoantibodies directed against components of the nucleus, the test can also be used to detect antibodies directed against cellular components that are contained within the cell cytoplasm, outside of the nucleus.
Because symptoms of autoimmune disorders often vary from patient to patient, these diseases may be very difficult to diagnose. Together with a healthcare provider’s careful consideration of a patient’s symptoms, physical findings, and other laboratory test results, a positive ANA test may assist in the diagnosis of autoimmune diseases.
INTERPRETING ANTINUCLEAR ANTIBODIES RESULTS
In the ANA test, antinuclear (or anti-cytoplasmic) antibodies bind to cells that have been fixed on a slide. The addition of a secondary antibody (with an attached fluorescent dye) directed against human antibodies may reveal staining of the nucleus or cytoplasm under a fluorescence microscope. Patient samples are often screened for ANA after being diluted 1:40 and 1:160 in a buffered solution. If staining is observed at both the 1:40 and 1:160 dilutions, then the laboratory continues to dilute the sample until staining can no longer be seen under the microscope. The level to which a patient’s sample can be diluted, and still produce recognizable staining, is known as the ANA “titer.” The ANA titer is a measure of the amount of ANA in the blood; the higher the titer, the more autoantibodies are present in the sample.
It is difficult to standardize the ANA test between laboratories. One approach has been to modify the test reagents such that 30 percent of normal individuals will have a positive test when their sample is tested at a dilution of 1:40. This standardization makes the ANA test very sensitive for the diagnosis of autoimmune diseases but results in many false positive results. At a dilution of 1:160, only 5 percent of normal individuals have a positive test for ANA. The 1:160 dilution increases the specificity of the ANA test for the diagnosis of autoimmune diseases.
ANTINUCLEAR ANTIBODIES TESTING
- A positive test for ANA may assist healthcare providers in establishing the diagnosis of an autoimmune disease and may help determine the specific type of autoimmune disease that is affecting a patient.
- A negative test for ANA may assist healthcare providers by decreasing the likelihood that a patient’s symptoms are caused by an autoimmune disease.
THE SIGNIFICANCE OF ANTINUCLEAR ANTIBODIES
Patients with the following systemic autoimmune diseases may have a positive test for ANA:
Patients with organ-specific autoimmune diseases may also have a positive test for ANA. These diseases include:
- Thyroid diseases (Hashimoto’s thyroiditis, Grave’s disease)
- Gastrointestinal diseases (autoimmune hepatitis, primary biliary cirrhosis, inflammatory bowel disease)
- Pulmonary diseases (Idiopathic pulmonary fibrosis)
Patients with infectious diseases may also test positive for ANA. These diseases include:
- Viral infections (Hepatitis C, Parvovirus)
- Bacterial infections (Tuberculosis)
- Parasitic infections (Schistosomiasis)
Other associations with positive ANA tests have been noted, including:
- Various forms of cancer (rarely)
- As a harbinger of the future development of autoimmune disease
- Various medications, without causing an autoimmune disease
- Having one or more relatives with an autoimmune disease
Some individuals, even those without a relative with autoimmune disease, may have a positive test for ANA and yet never develop any autoimmune disease.
TYPES OF ANTINUCLEAR ANTIBODIES
If a patient has a positive test for ANA, his or her healthcare provider, depending on the patient’s symptoms or findings on physical examination, may order additional tests to identify specific types of autoantibodies. Some examples are provided below:
Systemic lupus erythematosus (SLE) — If a diagnosis of SLE is suspected, then additional tests, looking for autoantibodies directed against double-stranded DNA, Sm antigens, and ribosomal P antigens may be ordered. Because these antibodies are relatively specific for SLE, the results may provide important clues to facilitate the diagnosis of SLE. (See "Patient information: Systemic lupus erythematosus (SLE) (Beyond the Basics)".)
Sjögren’s syndrome — If a diagnosis of Sjögren’s syndrome is suspected, the healthcare provider may test for autoantibodies directed against antigens known as Ro/SSA and La/SSB. The presence of these autoantibodies provides support for the diagnosis of Sjögren’s syndrome, a disorder which involves autoimmune destruction of the glands that produce tears and saliva.
Drug-induced SLE — If a diagnosis of drug-induced SLE is suspected, then a test for antihistone antibodies may be ordered. Antihistone antibodies are nearly always present in patients with drug-induced SLE. If antihistone antibodies are not detected, then the likelihood of this diagnosis (drug-induced SLE) is greatly reduced.
A WORD OF CAUTION
A positive test for ANA does not, by itself, indicate the presence of an autoimmune disease. As mentioned above, because of the design of the ANA test, many normal individuals will have a positive test at low titers. Even when detected at high titer, a positive ANA result, by itself (in the absence of symptoms or physical findings), does not indicate that a patient either has, or will develop, an autoimmune disease. Some ANA appear to be unrelated to the development of autoimmune disorders. Future studies may help identify these “benign” autoantibodies and may permit healthcare providers to provide reassurance to their patients.
WHERE TO GET MORE INFORMATION
Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
This topic currently has no corresponding Basic content.
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Patient information: Systemic lupus erythematosus (SLE) (Beyond the Basics)
Patient information: Polymyositis, dermatomyositis, and other forms of idiopathic inflammatory myopathy (Beyond the Basics)
Patient information: Rheumatoid arthritis symptoms and diagnosis (Beyond the Basics)
Patient information: Vasculitis (Beyond the Basics)
Patient information: Sjögren’s syndrome (Beyond the Basics)
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Antibodies to double-stranded (ds)DNA, Sm, and U1 RNP
Antiribosomal P protein antibodies
Diagnosis and differential diagnosis of systemic lupus erythematosus in adults
Investigational biologic markers in the diagnosis and assessment of rheumatoid arthritis
Measurement and clinical significance of antinuclear antibodies
Miscellaneous antinuclear antibodies
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