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), it 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.¹

This article describes the major tests used to diagnose and evaluate SLE and provides information on their rationale and clinical usefulness.

Diagnostic testing relies on two concepts, sensitivity and specificity. The first term refers to whether a test is likely to miss many cases of the disease or disorder for which the patient is being tested. The second refers to whether the test is helpful in narrowing the diagnosis to the condition being tested for.²

Antinuclear Antibody (ANA)

A positive result for the presence of these antibodies, which your immune system produces, means your immune system is "stimulated". That's a common finding if you have SLE or another autoimmune disease. The ANA is 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.¹ ANA testing is thus highly sensitive but not specific.² The sensitivity and specificity of ANA determinations depend on the technique used.¹

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.¹ It may be unique to SLE; a finding with low sensitivity but high specificity.²

Anti-dsDNA

Anti-dsDNA is an immunoglobulin specific against native (double stranded) DNA. This test is highly specific for SLE but not particularly sensitive and it is not found in patients with other rheumatic diseases. Anti-dsDNA is found in at least 50% of SLE patients at some time.³ For many patients with anti-dsDNA, the titer is a useful measure of disease activity. The presence of anti-dsDNA is associated with a greater risk of lupus nephritis.¹

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 people with SLE and 60% of patients with primary Sjogren's Syndrome. Anti-Ro is highly associated with photosensitivity both are associated with neonatal lupus.¹ These antibodies often accompany the Anti-Sm.²

Complement

Complement proteins constitute a serum enzyme system that helps mediate inflammation. Complement components are triggered into an activated for by such immunologic events as interaction with 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 C3 and C4.¹ The total amount of complement in the body at any given moment is finite. Therefore, if a complement has been drawn to sites of immune complex activity, there will be lower than normal levels in general circulation. In SLE, at least in active disease, serum complement levels are low. This pattern is also helpful in monitoring treatment.²

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

Tests for ESR and CRP are nonspecific tests to detect generalized inflammation. It's specificity is very low but it does indicate something is amiss. Levels are generally increased in patients with active SLE and decline when corticosteroids or nonsteroidal anti-inflammatory drugs are used to reduce inflammation. However, they do not directly reflect disease activity.³

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, β2 glycoprotein 1) or protein-phospholipid complexes rather than phospholipids alone. APLs are present in 50% of people with SLE. Antiphospholipid Antibody Syndrome occurs in 50% 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- β2 glycoprotein 1 in the clinical setting of thrombosis, fetal loss, multiple first trimester losses, or preterm birth from severe placental vasculopathy.

APLs and Antiphospholipid Antibody Syndrome (APS) may also occur is patients without SLE. APLs are detected in 3 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 tme (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 manifestation of the Antiphospholipid Antibody Syndrome. Most lupus anticoagulant antibodies are directed against β2 glycoprotein 1 or prothrombin.

• Anticardiolipin antibodies (aCLs). Sensitive enzymes-linked immunoabsorbent assays (ELISAs) using cardiolipin as the putative antigen are commonly performed to detect aCLs. In patients with Antiphospholipid Antibody Syndrome, most antibodies detected in the Anticardiolipin ELISAs are directed against the cardiolipin-bound β2 glycoprotein 1.

• anti- β2 glycoprotein 1. Because ELISAs do not recognized cardiolipin unless β2 glycoprotein 1 is present, anti- β2 glycoprotein 1 detection assays have been developed. These assays have revealed that anti- β2 glycoprotein 1 antibodies may be more strongly associated with Antiphospholipid Antibody Syndrome than are the anticardiolipins.¹

Clinically, APS has also been associated, in significant proportions of patients, with several other disorders. They include particular neurological problems, notable seizures or migraine headaches; joint pain and inflammation; livedo reticularis, patch discoloration of the skin caused by dilation of small blood vessels; avascular necrosis of bone (even when corticosteroids, with which this condition usually associated, are not being taken); leg ulcers; hemolytic anemia; and various other troubles traceable chiefly to circulatory problems, including thromboses both major and minor. All APS-related difficulties are exacerbated by smoking and uncontrolled blood pressure, diabetes, and high cholesterol.²

Resources:

1: Lupus: A Patient Care Guide for Nurses and Other Health Professionals. 3^rd Edition, National Institutes of Health, National Institute of Arthritis & Musculoskeletal & Skin Diseases. 2006

2: Living with Lupus: The Complete Guide, written by Sheldon Paul Blau, MD & Dodi Schultz, 2^nd ed., rev. and updated 2004

3: Lupus: You Can Take Charge of It, written by Victoria Scanlan Stefanakos, 2005

Tina is the President, Co-Founder, Executive Director of the APS Foundation of America, Inc and APS Patient.

Founded in 2005, the APS Foundation of America, Inc. is the leading United States nonprofit health agency dedicated to bringing national awareness to Antiphospholipid Antibody Syndrome (APS), the major cause of multiple miscarriages, thrombosis, young strokes and heart attacks. We are a volunteer run, community based 501(c)3 non-profit Public Charity organization and is dedicated to fostering and facilitating joint efforts in the areas of education, support, public awareness, research and patient services. Their URL is http://www.apsfa.org