| 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 Sjögren’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 Sjögren’s syndrome. Anti-La
is found in 15% of lupus patients and 60% of patients
with primary Sjögren’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 phospholipid-binding
plasma proteins (e.g., prothrombin, ß2-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 thrombo- embolism 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 microhemagglutination-Treponema
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 ß2-glycoprotein I.
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 ß2-glycoprotein I.
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