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Measurements of Autoimmunity

The presence of certain autoantibodies have diagnostic value for SLE. The most specific tests are those that detect high levels of these autoantibodies.

The most common and specific tests for autoantibodies and other elements of the immune system are listed first.

Antinuclear Antibody (ANA)

A screening test for ANA is standard in assessing SLE because it is positive in close to 100% of patients with active SLE.

However, it is also positive in 95% of patients with mixed connective tissue disease, in more than 90% of patients with systemic sclerosis, in 70% of patients with primary Sjogren's syndrome, in 40-50% of patients with rheumatoid arthritis, and in 5-10% of patients with no systemic rheumatic disease.

Patients with SLE tend to have high titers of ANA. False-positive results are found during chronic infectious diseases, such as subacute bacterial endocarditis, tuberculosis, hepatitis, and malaria.

The sensitivity and specificity of ANA determinations depend on the technique used.

Anti-Sm

Anti-Sm is an immunoglobulin specific against Sm, a ribonucleoprotein found in the cell nucleus.

This test is highly specific for SLE; it is rarely found in patients with other rheumatic diseases.

However, only 30% of patients with SLE have a positive anti-Sm test.

Anti-nDNA

Anti-nDNA is an immunoglobulin specific against native (double-stranded) DNA. This test is highly specific for SLE; it is not found in patients with other rheumatic diseases.

Sixty to eighty percent of patients with active SLE have a positive anti-nDNA test.

For many patients with anti-nDNA, the titer is a useful measure of disease activity.

The presence of anti-nDNA is associated with a greater risk of lupus nephritis.

Anti-Ro(SSA) and Anti-La(SSB)

These immunoglobulins, commonly found together, are specific against RNA proteins.

Anti-Ro is found in 30% of SLE patients and 70% of patients with primary Sjogren's syndrome.

Anti-La is found in 15% of lupus patients and 60% of patients with primary Sjogren's syndrome. Anti-Ro is highly associated with photosensitivity; both are associated with neonatal lupus.

Complement

Complement proteins constitute a serum enzyme system that helps mediate inflammation.

Complement components are triggered into an activated form by such immunologic events as interaction with immune complexes.

Complement components are identified by numbers (C1, C2, etc.).

Genetic deficiencies of C1q, C2, and C4, although rare, are commonly associated with SLE.

A test to evaluate the entire complement system is called CH50. The most commonly measured complement components are the serum level of C3 and C4.

These tests are particularly useful in evaluating kidney involvement and in monitoring the disease over time.

Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP)

Tests for ESR and CRP are nonspecific tests to detect generalized inflammation.

Levels are generally increased in patients with active lupus and decline when corticosteroids or NSAIDs are used to reduce inflammation.

Antiphospholipid Antibodies (APLs)

APLs are autoantibodies that react with phospholipids.

Recent data indicate that APLs recognize a number of phospholipidbinding plasma proteins (e.g., prothrombin, B2-glycoprotein I) or protein-phospholipid complexes rather than phospholipids alone.

APLs are present in 30--40% of lupus patients. A positive APL test plus the presence of arterial and venous thrombosis and thromboembolism or recurrent fetal deaths or thrombocytopenia is called APL syndrome.

APL syndrome affects about a third of lupus patients with APLs (10-15% of all lupus patients). APLs and APL syndrome may also occur in patients without lupus (primary APL syndrome). APLs are detected in the following three types of laboratory assays.

Syphilis Serology

Certain blood tests for syphilis may be falsely positive in lupus patients. Chronically false-positive VDRL or rapid plasma reagin (RPR) tests may occur in patients with lupus.

Cardiolipin, a phospholipid, is a component of the antigenic mixture used in these assays.

More specific tests for syphilis, such as the fluorescent treponemal antibody-absorbed (FTA-ABS) and microhemagglutinationTreponema pallidum (MHA-TP) assays, are almost always negative in lupus patients without syphilis.

Anticardiolipin Antibody (ACA) Sensitive enzyme-linked immunoabsorbent assays (ELISA) using cardiolipin as the putative antigen are commonly used to detect APLs.

In patients with APL syndrome, most antibodies detected in anticardiolipin ELISAs are directed against cardiolipin-bound B2-glycoprotein 1.

Lupus Anticoagulant

Lupus anticoagulants are APLs that inhibit certain coagulation tests, such as the activated partial thromboplastin time (aPTT), dilute Russell viper venom time (dRVVT), and kaolin clotting time (KCT).

Although the antibodies act as anticoagulants in these laboratory assays, they are not clinically associated with hemorrhage, but with thrombosis and other manifestations of the APL syndrome.

Most lupus anticoagulant antibodies are directed against prothrombin or B2-glycoprotein 1.



Source: National Institutes of Health, U.S.Dept of Health and Human Services



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