Lab Tests used to diagnose Lupus

Laboratory Testing In
Systemic Lupus Erythematosus 
By Susan A. Baker, M.D. and Rodney Bluestone, M.B., M.R.C.P 
 
Laboratory testing in Systemic Lupus Erythematosus (SLE) serves several important functions: making a diagnosis, monitoring the activity of the disease, monitoring response to treatment, and detecting side effects of medications. This review of common laboratory testing in SLE will summarize the lab tests most commonly ordered by your rheumatologist and how these tests are interpreted. Because there is no specific test for SLE, your doctor must rely on a number of different factors to make a diagnosis including history, physical exam and laboratory data. The laboratory data therefore plays an essential role. 
 
Table 1. LABORATORY ASSESSMENT in lupus 
LABORATORY TESTS 
1. General Tests 
Urinalysis 
Leukocyte Count 
Hematocrit 
Platelet Count 
Creatinine/Blood Chemistry 
Plasma Proteins 
Erythrocyte Sedimentation Rate 
C-Reactive Protein 
Blood Glucose 
Cholesterol 
2. Immune Testing 
ANA 
Anti-Sm 
anti-dsDNA 
anti-Ro (SS-A) 
anti-La (SS-B) 
anti-Histone 
anti-RNP 
Lupus Anticoagulant 
Anti-Cardiolipan Antibody 
Beta-2 Glycoprotein I 
Complement 
Cryoglobulins 
 
 
Urinalysis - This exam can measure the protein and cells in your urine which can be an early warning of kidney disease in lupus patients. 
 
Complete blood count (CBC) - measures the cell counts in your blood which include white blood cells, red blood cells, hemoglobin and platelet counts. White blood cells can be decreased in lupus and may be a sign of active disease or drug-related side effect. Patients with lupus may have a mild anemia manifested by a low hemoglobin level. Causes of anemia include iron deficiency, active inflammation or less frequently, hemolytic anemia which is caused by autoantibodies to red blood cells. Worsening anemia may be a sign of increased disease activity and may be a useful guide to monitor response to treatment. Thrombocytopenia manifested by low platelet counts may be one of the earlier features of lupus and is thought to be related to anti-platelet antibodies. 
 
Creatinine/Blood Chemistry - Serum creatinine is also a measure of kidney function and rises when the kidney is functioning abnormally. Because the kidneys are one of the primary target tissues in SLE, close monitoring is of great importance. In addition, a number of anti-rheumatic medications can cause injury to the kidney that may be reversed when detected early. 
 
Plasma Proteins - Serum albumin and gamma globulin measurements provide additional clues of systemic rheumatic disease. A low serum albumin concentration may be seen in SLE patients as a result of active inflammation, malnutrition or kidney disease. Elevated levels of gamma globulins (IgG, IgA, IgM) are a sign of immune activation. 
 
Erythrocyte sedimentation rate (ESR) - is a non-specific sign of inflammation. In lupus patients, the ESR may be elevated with active disease or with concomitant infection. It is a non-specific inflammatory marker that is useful for monitoring disease flares and therapeutic response to treatment. 
 
C-Reactive Protein (CRP) - is a plasma protein produced by liver cells during episodes of acute inflammation. Elevated CRP levels may be suggestive of active infection in SLE patients or may rarely correlate with disease flares. Recent studies have shown that an elevated level may also be a risk factor for cardiovascular disease. 
 
CARDIOVASCULAR RISK SCREENING
We are now aware that patients with SLE are fifty times more likely to develop cardiovascular disease including strokes and heart attacks than the general population. Regular screening for cardiovascular risk factors including diabetes and hyperlipidemia is therefore essential. Blood glucose, homocysteine and cholesterol measurements, especially LDL (fasting) are routinely monitored. 
 
AUTOANTIBODIES
Laboratory tests used to diagnosis and monitor lupus include the identification of autoantibodies made inappropriately by the immune system in SLE. Under normal conditions antibodies are proteins that are made by your immune system to fight infection. In SLE these antibodies are misdirected against normal cellular components, forming immune complexes, which are potentially damaging to various tissues in the body in which they may deposit. 
 
Antinuclear Autoantibody (ANA) - is an antibody directed against material in the nucleus of cells and is the initial screening test for lupus. The ANA test is reported as a titer and a pattern. The titer represents the number of times the blood needs to be diluted to eliminate the autoantibody from serum. A higher titer, therefore, represents a higher level of autoantibody in the serum although this is not a reliable measurement of disease activity. The pattern of ANA seen on immunofluorescence may be associated with different autoimmune diseases. Any pattern can be seen in SLE but the peripheral (or rim) pattern is the most specific. While 95% of lupus patients have a positive ANA, a small subset of lupus patients are ANA negative. In addition, 5% of the general population have a positive ANA and (never develop any clinical evidence of) lupus and the chances of this increases with age. A positive ANA test can be seen in a number of conditions, including autoimmune disease, chronic infections, post acute viral infections, or may be induced by certain medications. A positive ANA must, therefore, be interpreted within the context of a patient's symptoms and is not sufficient alone to make a diagnosis of lupus. More specific testing for the individual types of antoantibodies including anti-dsDNA, anti-Sm, anti-RNP, anti-Ro, anti-La are important in defining the underlying disease. 
 
Double-stranded DNA autoantibodies (dsDNA) - are antibodies directed against genetic material in the cell. They are found in the majority of patients with lupus and elevated levels are characteristic of lupus affecting the kidneys. These autoantibodies are highly specific for lupus and are only rarely associated with other autoimmune diseases or infections. These autoantibodies have been found to fluctuate with disease activity and are a useful tool for monitoring disease flares and remissions. 
 
Sm (Smith) Autoantibodies - are antibodies against nuclear material in the cell. They are highly specific for SLE and are not described in other diseases. Unlike anti-dsDNA autoantibodies, anti-Sm autoantibodies are not useful for monitoring disease activity. 
 
SS-A/Ro, SS-B/La Antoantibodies - are antibodies to cellular proteins. They may be found in a number of autoimmune diseases, most commonly Sjogren's syndrome. SS-A autoantibody in particular is associated with certain clinical features of SLE including skin lesions and neonatal SLE including congenital heart block. It can also be found in ANA negative SLE. 
 
Histone Autoantibodies - are antibodies directed against nuclear material in the cell. While they are present in many patients with lupus, the presence of this antibody is characteristic of drug-induced lupus. 
 
RNP Autoantibodies - are antibodies to small proteins in the nucleus (ribonuclear proteins). While RNP autoantibodies can be seen in a number of autoimmune diseases, high levels are characteristic of Mixed Connective Tissue disease, an autoimmune disease with clinical features overlapping SLE and Scleroderma. 
 
Antiphopholipid Antibodies - are antibodies directed against blood proteins, which bind to the surface of blood vessel walls and platelets. These autoantibodies include lupus anticoagulants (LA), anti-cardiolipan antibodies, anti- B2-glycoprotein I, antibodies responsible for a false positive VDRL (syphilis) test and anti-prothrombin antibodies. This group of autoantibodies is associated with an elevated risk of blood clotting, multiple spontaneous miscarriages and low platelet counts. While most patients remain asymptomatic, a small percentage of patients develop one of these illnesses and are said to have antiphopholipid (apL) syndrome which sometimes requires life-long anticoagulation to prevent future blood clotting. These autoantibodies can be associated with autoimmune disease (mostly SLE), chronic infections or may be related to medication use. 
 
Complement (C3, C4, CH50) - a group of enzymatic proteins (C1-C9) found in normal blood serum that participate and are consumed in the inflammatory process. Decreased levels of one or all three proteins can be seen in SLE and may signify kidney disease. In addition, low levels of complement with or without elevated levels of dsDNA may herald a disease flare. While findings are variable, serial monitoring of complement proteins may be used to predict a disease exacerbation. An inherited deficiency in one of these proteins may also predispose to developing SLE. 
 
Cryoglobulins - are immune complexes that form in SLE patients as a result of autoantibodies interacting with abnormal cellular components. These immune complexes may then deposit in tissues causing inflammation and damage. Detection of serum cryoglobulins serves as a crude indication of immune complexes circulating in the blood of SLE patients and may be related to the activity of the disease. 
 
CONCLUSION
Systemic Lupus is a chronic autoimmune disease with an unpredictable course. Because lupus is a potentially life-threatening disease, regular laboratory evaluation is essen tial in illustrating the variable manifestations of this disease. Early recognition of complications with careful clinical and laboratory assessment minimizes flares, side effects of medications and can allow patients to live healthy and productive lives.