Anti-dsDNA

The anti-double stranded DNA (anti-dsDNA) test is used to help diagnose lupus (systemic lupus erythematosus, SLE) in a person who has a positive result on a test for antinuclear antibody (ANA) and has clinical signs and symptoms that suggest lupus.

Anti-dsDNA is one of a group of autoantibodies called antinuclear antibodies that are produced by a person's immune system when it fails to distinguish between "self" and "nonself." ANA target substances found in the nucleus of cells. Anti-dsDNA specifically target the genetic material (DNA) found in the nucleus, causing organ and tissue damage. The presence of anti-dsDNA in the blood is strongly associated with the autoimmune disorder lupus.

Typically, an ANA test is the first test performed to evaluate an individual for an autoimmune disorder. While a positive ANA test is seen in about 95% of lupus cases, it may be seen in many other conditions as well. The anti-dsDNA test is fairly specific for lupus; however, only 50-70% of people with lupus may be positive; that is, a negative anti-dsDNA does not rule out lupus. If a person has a positive ANA, an anti-dsDNA test may be used to distinguish lupus from other autoimmune disorders that have similar signs and symptoms.

An anti-dsDNA test may be ordered along with a test for anti-Sm (Smith antibody), another antinuclear autoantibody associated with lupus, to help establish a diagnosis. The anti-Sm test may be ordered as part of an extractable nuclear antigen (ENA) panel. Depending upon clinical signs and the health practitioner's suspicions, other autoantibodies may also be ordered to help distinguish between, and rule out, other autoimmune disorders. Examples include tests for histone antibody (drug-induced lupus) and antiphospholipid antibodies.

The anti-dsDNA test may be used to monitor the severity of the disease in a person who has been diagnosed with lupus. Those with lupus often have flare-ups in which symptoms worsen and then subside. An increased anti-dsDNA level may be seen prior to and during these flare-ups. In particular, this test may be used to monitor lupus nephritis, a serious complication of lupus that can cause kidney damage and inflammation. This can lead to protein in the urine, high blood pressure, and kidney failure. It occurs when the autoantibodies bind to antigens and become deposited in the kidneys.

An anti-dsDNA test is ordered when a person shows signs and symptoms that could be due to lupus and has had a positive ANA test, especially when the result of the ANA test presents as a "homogeneous" or "speckled" fluorescent pattern. (See the article on ANA for more on this.)

Examples of some signs and symptoms of lupus include:

• Musclepain
• Arthritis-likepain in one or more joints (but no or little joint damage)
• Redrash that frequently resembles a butterfly across the nose and cheek areas(malar rash)
• Low-grade fever
• Persistentfatigue, weakness
• Skin sensitivityto light
• Hair and weight loss
• Numbness or tingling in the hands or feet
• Inflammationand damage to organs and tissues, including the kidneys, lungs, heart,lining of the heart, centralnervous system, and blood vessels

The anti-dsDNA test may be ordered periodically to monitor progress of the disease or flare-ups in a person who has been diagnosed with lupus. It may be repeated when an initial test result is negative but clinical signs and symptoms persist and lupus is strongly suspected. 

The results of an anti-dsDNA test are usually considered together with a person's medical history, signs and symptoms, and results of other autoantibody tests.

A high level of anti-dsDNA in the blood is strongly associated with lupus and is often significantly increased during or just prior to a flare-up. When the anti-dsDNA is positive and the person tested has other clinical signs and symptoms associated with lupus, it means that the person tested likely has lupus. This is especially true if an anti-Sm test is also positive.

In the evaluation of someone with lupus nephritis, a high level (titer) of anti-dsDNA is generally associated with ongoing inflammation and damage to the kidneys.

A very low level of anti-dsDNA is considered negative but does not exclude a diagnosis of lupus. Only about 50-70% of those with lupus will have anti-dsDNA.

Low to moderate levels of the autoantibody may be seen with other autoimmune disorders, such as Sjögren syndrome and mixed connective tissue disease (MCTD).

Anti-dsDNA tests are semi-quantitative tests and may be performed using different assays. Many laboratories use an anti-dsDNA ELISA test (enzyme-linked immunoabsorbent assay), a very reliable and sensitive test.

Anti-dsDNA is sometimes present with diseases such aschronic hepatitis, primary biliary cirrhosis, and infectious mononucleosis. It may also be seen in those taking drugs such as procainamide and hydralazine. It is not usually tested or monitored under these conditions.

In addition to testing for anti-double-stranded DNA, there is also an anti-single-stranded DNA test. This autoantibody is less commonly tested and is not strongly associated with lupus but may be seen with other autoimmune disorders.

ANA consists of a group of antinuclear antibodies. If an ANA test is negative, it indicates that the entire group is negative. Since anti-dsDNA is a member of this group, it does not need to be ordered separately when an ANA test is negative.