Antinuclear antibodies (ANA)

Antinuclear antibodies (ANA)

Author
Morris Reichlin, MD
Section Editor
Robert H Shmerling, MD
Deputy Editor
Paul L Romain, MD

Disclosures

ANTINUCLEAR ANTIBODIES OVERVIEW — A test for antinuclear antibodies (ANA) test is common in people who are suspected of having an autoimmune or connective tissue disorder. Antibodies are proteins that are made as part of an immune response. Normally the immune system responds to infection by producing large numbers of antibodies to fight bacteria or viruses. However, when a person has an autoimmune disease, the body’s immune system malfunctions, producing large amounts of harmful substances called autoantibodies.

Autoantibodies, unlike normal antibodies that fight bacteria, viruses, parasites, and fungi, attack the body’s own tissues and cells. Autoantibody-mediated inflammation and cell destruction can affect blood cells, skin, joints, kidneys, lungs, nervous system, and other organs of the body.

The ANA test identifies autoantibodies that target substances contained in the nucleus of cells. Symptoms of autoimmune and connective tissue disorders vary from patient to patient and may be difficult to diagnose. A positive ANA test, by itself, does not establish a diagnosis. However, when considered in combination with an individual’s symptoms, a thorough physical examination, and other laboratory testing, a positive test result may help to establish a diagnosis.

ANTINUCLEAR ANTIBODIES TESTING — The results of an ANA test may be used in one or more ways:

To aid in diagnosis of an autoimmune or connective tissue disorder
To rule out autoimmune or connective tissue disorders in people who have only a few symptoms
To measure how active a person’s disease is
To determine the specific type of disease that affects the patient
DISEASES AND ANTINUCLEAR ANTIBODIES RESULTS — People with the following disorders or characteristics may have positive ANA tests:

Systemic lupus erythematosus (see “Patient information: Systemic lupus erythematosus (SLE)”).
Scleroderma
Mixed connective tissue disease
Polymyositis/dermatomyositis (see “Patient information: Myositis”)
Rheumatoid arthritis (see “Patient information: Rheumatoid arthritis symptoms and diagnosis”)
Rheumatoid vasculitis (see “Patient information: Vasculitis”)
Sjögren’s syndrome (see “Patient information: Sjögren’s syndrome”)
Drug-induced lupus
Discoid lupus
Pauciarticular juvenile chronic arthritis
In addition, some people with autoimmune diseases that affect the thyroid gland, liver, or lung (including Hashimoto’s thyroiditis, Graves’ disease, autoimmune hepatitis, primary biliary cirrhosis, primary autoimmune cholangitis, and idiopathic pulmonary arterial hypertension) can have a positive ANA test.

Certain infectious diseases, such as mononucleosis, hepatitis C virus infection, subacute bacterial endocarditis, tuberculosis, lymphoproliferative diseases, and human immunodeficiency virus (HIV), may also produce a positive ANA test.

TYPES OF ANTINUCLEAR ANTIBODIES — Certain types of antinuclear antibodies are somewhat specific to certain diseases or forms of diseases. The main types of antinuclear antibodies include the following:

Antibodies to double-stranded DNA — People with systemic lupus erythematosus or rheumatoid arthritis, or people who have been exposed to drugs, including tumor necrosis factor alpha inhibitors (often used in the treatment of rheumatoid arthritis, inflammatory bowel disease, and some cancers), may have moderate to high levels of antibodies to deoxyribonucleic acid (DNA).

Antibodies to histone proteins — People with systemic lupus erythematosus or drug-induced lupus may make antibodies to certain histone protein molecules that are found in chromosomes.

Antibodies to chromatin — More than two-thirds of people with SLE have antibodies to chromatin, a mixture of nucleic acid and proteins. Anti-chromatin antibodies are especially prevalent in SLE patients with renal (kidney) disease.

ANTINUCLEAR ANTIBODIES AND SYSTEMIC LUPUS ERYTHEMATOSUS — In a person with suspected systemic lupus erythematosus (SLE), the ANA test plays an important role in the diagnosis. SLE is a chronic inflammatory disease that can affect many parts of the body, including the skin, joints, kidneys, lungs, nervous system, blood vessels, and immune system.

Because the severity and symptoms of SLE differ from patient to patient, laboratory tests – including testing for antinuclear antibodies – provide information that can be valuable in helping to diagnose SLE. The ANA test is considered the best diagnostic test for SLE, and it is typically performed whenever SLE is suspected. (See “Patient information: Systemic lupus erythematosus (SLE)”.)

In people with suspected or diagnosed systemic lupus erythematosus, additional testing may be performed to determine the presence of three specific types of antinuclear antibodies, including anti-DNA, anti-Smith (anti-Sm), and anti-ribonucleoprotein (anti-RNP) antibodies. When positive, these tests are considered highly predictive of SLE. Testing for anti-DNA antibodies may also be a sign of disease activity in the kidneys. Anti-DNA antibody levels may also be monitored.

INTERPRETING ANTINUCLEAR ANTIBODIES RESULTS — Antinuclear antibodies bind to the nuclei of cells on a slide and produce a recognizable pattern when a stain is applied. The number of times the blood must be diluted until the antibody can no longer be detected is known as the “titer”; this is a commonly used measure of the level of ANA present in the blood. Thus, a titer of 1:40 means that, after the blood is diluted more than 40-fold, the ANA is no longer detectable.

Both the titer and the staining pattern can help establish the diagnosis of autoimmune or connective tissue disorders. Certain illnesses may be associated with certain patterns of staining; however, the titer is considered the most relevant part of the ANA test. In general, the higher the titer, the more likely there is an associated disease present. Low titers of ANA are found many healthy people.

To detect the presence of specific autoantibodies (such as antibodies to double-stranded DNA, individual histones, or chromatin), further testing is usually necessary.

Positive antinuclear antibody — A positive ANA test does not necessarily mean that the person has lupus or another connective tissue disorders. As noted earlier, many healthy people may have a positive ANA test.

False positive results — The ANA test is said to be false positive when a person tests positive but does not have any other features of autoimmune disease . This situation occurs more often in women and elderly people. Certain medications, such as hydralazine, isoniazid, procainamide, and some anticonvulsant medications increase the chances of having a positive ANA test [1].

True positive results — A healthcare provider may recommend that a patient who has pain and inflammation in multiple joints of the body, a strongly positive ANA, and a negative or low titer for rheumatoid factor undergo further ANA testing for specific autoantibodies (see ‘Types of antinuclear antibodies’ above).

Depending on the symptoms that led to the ANA testing, further evaluation for one or more of the disorders that are associated with a positive ANA may be necessary (see ‘Antinuclear antibodies and systemic lupus erythematosus’ above).

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

 

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:

Patient information: Systemic lupus erythematosus (SLE)
Patient information: Myositis
Patient information: Rheumatoid arthritis symptoms and diagnosis
Patient information: Vasculitis
Patient information: Sjögren’s syndrome

Professional Level Information:

Antibodies to DNA, Sm, and RNP
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
Significance of a positive ANA in young women with symmetric arthralgias

The following organizations also provide reliable health information.

Arthritis Foundation
(www.arthritis.org)

Lupus Foundation of America, Inc.
(www.lupus.org)

National Institute of Arthritis and Musculoskeletal and Skin Diseases
(www.niams.nih.gov)

National Library of Medicine
(www.nlm.nih.gov/medlineplus/ency/article/003535.htm)

REFERENCES
Solomon DH, Kavanaugh AJ, Schur PH, American College of Rheumatology Ad Hoc Committee on Immunologic Testing Guidelines. Evidence-based guidelines for the use of immunologic tests: antinuclear antibody testing. Arthritis Rheum 2002; 47:434.
Leisy, PS. “My ANA is positive . . . What does that mean?” Lupus News (a publication of the Lupus Foundation of America). Available online at www.lupus.org/webmodules/webarticlesnet/templates/new_empty.aspx?articleid=402&zoneid=76 (Accessed 8/5/2008).
Kavanaugh A, Tomar R, Reveille J, et al. Guidelines for clinical use of the antinuclear antibody test and tests for specific autoantibodies to nuclear antigens. American College of Pathologists. Arch Pathol Lab Med 2000; 124:71.