Lupus Blood Tests

Blood Tests Used in the Diagnosis of Lupus

Antibodies form in the body as a response to infection. When an invader (antigen) enters the bodywhite blood cells known as B lymphocytes react by making special types of proteins called antibodies. Antibodies are your body’s way of remembering an antigen; if it enters the body againthe antibodies will recognize itcombine with itand neutralize it to prevent you from becoming infected. Howeverwith autoimmune diseases such as lupusthe immune system can produce antibodies (auto-antibodies) that attack your body’s cells as though they were invaderscausing inflammationdamageand even destruction. Several blood tests can be performed to detect specific auto-antibodies and help make the diagnosis of lupus. These blood tests are not conclusive by themselvesbut combining the tests with certain physical findings can help to corroborate a diagnosis.

Anti-Nuclear Antibody (ANA) Test

Anti-nuclear antibodies (ANA) are autoantibodies to the nuclei of your cells. 98% of all people with systemic lupus have a positive ANA testmaking it the most sensitive diagnostic test for confirming diagnosis of the disease. The test for anti-nuclear antibodies is called the immunofluorescent antinuclear antibody test. In this testa blood sample is drawn and sent to a laboratory. Serum from the blood sample is then added to a microscopic slide prepared with specific cells (usually sections of rodent liver/kidney or human tissue culture cell lines) on the slide surface. If the patient has antinuclear antibodiestheir serum will bind to the cells on the slide. Thena second antibody tagged with a fluorescent dye is added so that it attaches to the serum antibodies and cells that have bound together. Lastlythe slide is viewed using a fluorescence microscopeand the intensity of staining and pattern of binding are scored at various dilutions. The test is read as positive if fluorescent cells are observed.

Usuallythe results of the ANA test are reported in titers and patterns. The titer gives information about how many times the lab technician diluted the blood plasma to get a sample of ANAs. Each titer involves doubling the amount of test fluidso that the difference between a titer of 1:640 and 1:320 is one dilution. A titer above a certain level then qualifies as a positive test result. ANA titers may increase and decrease over the course of the disease; these fluctuations do not necessarily correlate with disease activity. Thusit is not useful to follow the ANA test in someone already diagnosed with lupus.

The pattern of the ANA test can give information about the type of autoimmune disease present and the appropriate treatment program. A homogenous (diffuse) pattern appears as total nuclear fluorescence and is common in people with systemic lupus. A peripheral pattern indicates that fluorescence occurs at the edges of the nucleus in a shaggy appearance; this pattern is almost exclusive to systemic lupus. A speckled pattern is also found in lupus. Another patternknown as a nucleolar patternis common in people with scleroderma.

It is important to realize that even though 98% of people with lupus will have a positive ANAANAs are also present in healthy individuals (5-10%) and people with other connective tissue diseasessuch as scleroderma and rheumatoid arthritis. Moreoverabout 20% of healthy women will have a weakly positive ANAand the majority of these people will never develop any signs of lupus. One source cites that some ten million Americans have a positive ANAbut fewer than 1 million of them have lupus. Thereforea positive ANA test alone is never enough to diagnosis systemic lupus. Rathera physician will order an ANA test if the patient first exhibits other signs of lupus. This is because by itselfthe test has low diagnostic specificity for systemic lupusbut its value increases as a patient meets other clinical criteria. It is possible for people with lupus to have a negative ANAbut these instances are rare. In factonly 2% of people with lupus will have a negative ANA. People with lupus who have a negative ANA test may have anti-Ro/SSA or antiphospholipid antibodies.

Other Diagnostic Tests

In people with a positive ANAmore tests are usually performed to check for other antibodies that can help to confirm the diagnosis. Certain autoantibodies and substances in the blood can give information about which autoimmune diseaseif anyis present. To check for these antibodiesdoctors usually order what is called an ANA panelwhich checks for the following antibodies: anti-double-stranded DNAanti-Smithanti-U1RNPanti-Ro/SSAand anti-La/SSB. Some laboratories also include other antibodies in their panelincluding antinucleoproteinanticentromereor antihistone.

Anti-dsDNA Antibody

The anti-double-stranded DNA antibody (anti-dsDNA) is a specific type of ANA antibody found in about 30% of people with systemic lupus. Less than 1% of healthy individuals have this antibodymaking it helpful in confirming a diagnosis of systemic lupus. [The absence of anti-dsDNAhoweverdoes not exclude a diagnosis of lupus.] The presence of anti-dsDNA antibodies often suggests more serious lupussuch as lupus nephritis (kidney lupus). When the disease is activeespecially in the kidneyshigh amounts of anti-DNA antibodies are usually present. Howeverthe anti-dsDNA test cannot be used to monitor lupus activitybecause anti-dsDNA can be present without any clinical activity. Three tests are currently used to detect anti-dsDNA antibodiesnamely enzyme-linked immunosorbent assay (ELISA)the Crithidia luciliae immunofluorescence testand a test called radioimmunoassay.

Anti-Smith Antibody

An antibody to Sma ribonucleoprotein found in the nucleus of a cellis found almost exclusively in people with lupus. It is present in 20% of people with the disease (although the incidence varies among different ethnic groups)but it is rarely found in people with other rheumatic diseases and its incidence in healthy individuals is less than 1%. Thereforeit can also be helpful in confirming a diagnosis of systemic lupus. Unlike anti-dsDNAanti-Sm does not correlate with the presence of kidney lupus. Prospective studies have been performed as to whether anti-Sm correlates with lupus flares and disease activityalthough evidence seems to suggests that it does not. The anti-Sm antibody is usually measured by one of four methods: ELISAcounterimmunoelectrophoreses (CIE)immunodiffusionor hemagglutination.

Anti-U1RNP Antibody

Anti-U1RNP antibodies are commonly found along with anti-Sm antibodies in people with SLE. The incidence of anti-U1RNP antibodies in people with lupus is approximately 25%while less than 1% of healthy individuals possess this antibody. Howeverunlike anti-dsDNA and anti-Sm antibodiesanti-U1RNP antibodies are not specific to lupus; they can be found in other rheumatic conditionsincluding rheumatoid arthritissystemic sclerosisSjogren’s syndromeand polymyositis.
Anti-U1RNP has shown to be associated with features of sclerodermaincluding Raynaud’s phenomenon; it has also been linked to other conditionssuch as Jaccoud’s arthropathya deformity of the hand caused by arthritis. Levels of anti-U1RNP may fluctuate in individuals over timebut this fluctuation has not proven to be a significant indicator of disease activity.

Anti-Ro/SSA and Anti-La/SSB Antibodies

Anti-Ro/SSA and Anti-La/SSB are antibodies found mostly in people with systemic lupus (30-40%) and primary Sjogren’s syndrome. They are also commonly found in people with lupus who have tested negative for anti-nuclear antibodies. Anti-Ro and anti-La can also be found in other rheumatic diseasessuch as systemic sclerosisrheumatoid arthritisand polymyositisand are present in low titers in about 15% of healthy individuals. These antibodies are not highly specific for systemic lupusbut they are associated with certain conditionsincluding extreme sun sensitivitya clinical subset of lupus called subacute cutaneous lupus erythematosus (SCLE)and a lupus-like syndrome associated with a genetic deficiency of a substance called complement (a system of proteins that helps mediate your body’s immune response). In additionbabies of mothers with anti-Ro and anti-La antibodies are at an increased risk of neonatal lupusan uncommon condition that produces a temporary rash and can lead to congenital heart block. Thereforewomen with lupus who wish to become pregnant should be tested for these antibodies.

Anti-Histone Antibodies

Antibodies to histonesproteins that help to lend structure to DNAare usually found in people with drug-induced lupus (DIL)but they can also be found in people with systemic lupus. Howeverthey are not specific enough to systemic lupus to be used to make a concrete diagnosis.

Serum (blood) Complement Test

A serum complement test measures the levels of proteins consumed during the inflammatory process. Thuslow complement levels reflect that inflammation is taking place within the body. Variations in complement levels exist in different individuals simply due to genetic factors.

Sources

• “ANA.” 8 April 2009. Lab Tests Online. 8 April 2009. American Association for Clinical Chemistry. 6 July 2009. – Link
• “Blood Tests.” The Lupus Site. 6 July 2009. – Link
• “Laboratory Tests.” Lupus Foundation of America. 6 July 2009. – Link
• WallaceDaniel J. The Lupus Book: A Guide for Patients and Their Families. 1st ed. New York: Oxford University Press1995.
• WallaceDaniel J.and Bevra Hannahs Hahneds. Dubois’ Lupus Erythematosus. 7th ed. Philadelphia: Lippincott Williams & Wilkins2007.