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Publication Date: May 2001
Revised September 2006
Lupus: A Patient Care Guide for Nurses and Other Health Professionals
Chapter 3: Laboratory Tests Used to Diagnose and Evaluate Lupus
Lupus is characterized by abnormalities in many laboratory test results. These abnormalities are different for every patient and they vary significantly during the course of a patient’s disease. The serial evaluation of an individual’s tests along with the physician’s observations and the patient’s history determine the diagnosis of systemic lupus erythematosus (SLE), its course, and the treatment regimen. All laboratory values must be interpreted in light of the patient’s present status, other correlating laboratory test results, and coexisting illnesses. This chapter briefly describes the major tests used to diagnose and evaluate SLE and provides information on their rationale and clinical usefulness. Nurses and other health professionals should consult rheumatologists, manuals of laboratory and diagnostic tests, or hospital clinical laboratory departments for further information on possible interpretations of results from these tests and their implications for SLE.
Blood cell abnormalities often accompany SLE. People suspected of having lupus are usually tested for anemia, leukopenia, and thrombocytopenia.
Tests for anemia include those for hemoglobin, hematocrit, and red blood cell (RBC) counts. In addition, the levels of iron, total iron-binding capacity, and ferritin may be tested. At any time during the course of the disease, about 40 percent of patients with SLE will be anemic. The anemia may be caused by iron deficiency, gastrointestinal (GI) bleeding, medications, and autoantibody formation to RBCs, or “chronic disease.” When first diagnosed, about 50 percent of patients have a form of anemia in which the concentration of hemoglobin and the size of the RBCs are normal. This is called normochromic-normocytic anemia, or “anemia of chronic disease.” Autoimmune hemolytic anemia, with a positive Coombs test, is much less common.
Leukopenia and Thrombocytopenia
Abnormalities in the white blood cell (WBC) and platelet counts are an important indicator of SLE. Leukopenia, a decrease in the number of WBCs, is very common in active SLE and is found in 15 to 20 percent of patients. Leukopenia can occur from lupus or from prednisone. Thrombocytopenia, or a low platelet count, occurs in 25 to 35 percent of patients with SLE. This can be serious problem when platelet count is very low.
When certain autoantibodies are present, this provides valuable diagnostic information 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 percent of patients with active SLE. However, it is also positive in 95 percent of patients with mixed connective tissue disease, in more than 90 percent of patients with systemic sclerosis, in 70 percent of patients with primary Sjögren’s syndrome, in 40 to 50 percent of patients with rheumatoid arthritis, and in 5 to 10 percent of patients with no systemic rheumatic disease. Patients with SLE tend to have high titers of ANA. False-positive results are found during the course of 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 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 percent of patients with SLE have a positive anti-Sm test.
Anti-dsDNA 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. Fifty percent of patients with active SLE have a positive anti-dsDNA test. For many patients with anti-dsDNA, the titer is a useful measure of disease activity. The presence of antidsDNA 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 percent of SLE patients and 70 percent of patients with primary Sjögren’s syndrome. Anti-La is found in 15 percent of people with lupus and 60 percent of patients with primary Sjögren’s syndrome. Anti-Ro is highly associated with photosensitivity; both are associated with neonatal lupus.
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 levels of C3 and C4.
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 nonsteroidal anti-inflammatory drugs are used to reduce inflammation. However, they do not directly reflect disease activity.
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 50 percent of people with lupus. Antiphospholipid syndrome occurs in 50 percent of SLE patients who have the lupus anticoagulant. This syndrome is characterized by a persistently positive lupus anticoagulant or medium-to-high titer anticardiolipin or anti-ß2 glycoprotein I in the clinical setting of thrombosis, fetal loss, multiple first-trimester losses, or preterm birth from severe placental vasculopathy.
APLs and antiphospholipid syndrome may also occur in patients without lupus (primary antiphospholipid syndrome). APLs are detected in three types of laboratory assays:
- lupus anticoagulants. 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, pregnancy loss, and other manifestations of the antiphospholipid syndrome. Most lupus anticoagulant antibodies are directed against ß2 glycoprotein I or prothrombin.
- anticardiolipin antibodies (ACA). Sensitive enzymelinked immunoabsorbent assays (ELISAs) using cardiolipin as the putative antigen are commonly performed to detect APLs. In patients with antiphospholipid syndrome, most antibodies detected in anticardiolipin ELISAs are directed against cardiolipinbound ß2 glycoprotein I.
- anti-ß2 glycoprotein I. Because ELISAs do not recognize cardiolipin unless ß2 glycoprotein I is present, anti-ß2 glycoprotein detection assays have been developed. These assays have revealed that anti-ß2 glycoprotein I antibodies may be more strongly associated with antiphospholipid syndrome than are anticardiolipin antibodies.
Several tests can be done to assess a patient for kidney disease.
Measurement of Glomerular Filtration Rate and Proteinuria
The glomerular filtration rate is a measure of the efficiency of kidneys in filtering blood to excrete metabolic products. Typically this is done by collecting a 24-hour urine sample for measurement of creatinine clearance. Impairment of renal function by lupus nephritis results in reduced levels of creatinine clearance. The 24-hour urine sample can also quantify protein loss.
Performed on a one-time voided specimen, rather than from a 24-hour collection, this test is useful as a measure of protein loss and is more convenient for patients.
Urinalysis can indicate the presence or extent of renal disease. For example, proteinuria can be a reliable indicator of renal disease. The presence of RBCs, WBCs, and cellular casts, particularly red cell casts, in the urine also indicates renal disease.
Measurement of Serum Creatinine Concentration
Creatinine is a waste product of muscle metabolism that is excreted by the kidneys. Loss of renal function as a consequence of lupus nephritis causes increases in serum levels of creatinine. The concentration of creatinine in the serum can be used to assess the degree of renal impairment.
Kidney biopsy can be used to determine the presence of immune complexes and the presence, extent, and type of inflammation in the glomeruli. Diagnosing the extent and type of inflammation may help to determine a treatment program for lupus.