Adapted from a presentation at the SLE Workshop at Hospital for Special Surgery
Patients with suspected or confirmed systemic lupus erythematosus ("lupus" or SLE) undergo laboratory tests (blood tests) for multiple reasons. Physicians and other health care professionals test patients periodically and use the information derived from the tests in various ways.
Antinuclear antibody (ANA) autoantibodies, or antibodies produced by the immune system that attack the body’s own cells, are a hallmark of lupus. ANA is usually measured as 0 to 4+ or as a titer (the number of times a blood sample can be diluted and still be positive). ANA of 0, 1+ or 2+, or at titers less than 1:80 (diluted 80 times) usually do not indicate a significant problem. ANA titers at higher levels more likely indicate the presence of autoimmune disease. Many laboratories also measure pattern or the way the test looks when viewed through a microscope. Different ANA patterns may correspond with different characteristics of lupus.
ANA is a screening test, since almost all patients with lupus have a strongly positive test. However, a positive ANA test result does not by itself confirm a diagnosis for lupus. About 10% of people who do not have an autoimmune disease, as well as many who have other autoimmune diseases (such as thyroid disease) also have positive ANA tests, but usually less strongly positive. Once a person has a positive result, their ANA generally remains positive, so future ANA tests need not be repeated.
The anti-double-stranded DNA (dsDNA) antibody is named for its ability to bind to the normal DNA in patients’ cells. At high titers, this antibody is almost exclusively specific to people who have lupus. Low titers can occur in other rheumatic diseases, like rheumatoid arthritis and primary antiphospholipid syndrome. Sometimes, family members of people who have lupus may also test positive themselves, even though they do not have lupus. About 80% of patients with active, untreated lupus have a positive anti-dsDNA test. Monitoring anti-dsDNA is important, since levels may vary along with symptoms of disease, high titers indicating active disease, low titers quiescent disease. (However, anti-DNA antibody levels remain high in some patients with lupus who are well and do not need treatment.) Laboratories vary in how they report the test. Some do so as a range of 0 to 4+ (0, 1+, and 2+ are low titers; 3+ and 4+ are high), others as numbers. To know what is considered high you have to know the range used by the laboratory that conducted your test results.
A diagnosis of lupus is based on a combination of symptoms, physical examination abnormalities (for example, a rash or swollen joints), and laboratory tests. Not all patients with lupus have the anti-dsDNA antibody. Patients who have lupus but do not have anti-dsDNA often have a related antibody, anti-Sm.
Anti-Smith (anti-Sm), named for the first person known to have this antibody, is the antibody seen in most patients with lupus who do not have anti-dsDNA. Some patients have both anti-dsDNA and anti-Sm. Anti-Sm antibody binds to a protein that is attached to DNA. Unlike anti-dsDNA, the Sm antibody does not change in titer during a lupus flare or in response to treatment so need not be monitored.
Anti-RNP (anti-U1 ribonucleoprotein) is a non-specific antibody that occurs in many patients with lupus and other rheumatic diseases. When present in high titer − again, check how the laboratory reports its values to interpret the test − and in the absence of other autoantibodies, anti-RNP suggests a specific “lupus-like” disease, called mixed connective tissue disease (MCTD), characterized by symptoms of lupus, scleroderma, and dermatomyositis, that include:
Patients with MCTD, unlike those with SLE, have low risk for developing kidney disease.
Anti-Ro/SSA and anti-La/SSB antibodies identify other molecules in the cell nucleus. Two different groups of researchers discovered these antibodies almost simultaneously. One named them anti-Ro and anti-La for the first letters of the names of the patients in whom they were found; the other group named the antibodies SSA and SSB for Sjogren’s syndrome A and B, since they are characteristic of this illness. Most doctors use both names.
For technical reasons based on the size of the antigens (molecules to which the autoantibodies react), anti-Ro/SSA is subdivided into 60kd (kilodalton, the size of the molecule) and 52kd components, and La/SSB is 48kd. Distinguishing among them is useful in some special circumstances.
Patients with these antibodies:
Antiphospholipid antibodies (aPL) occur in about one-third of lupus patients. About 10% of lupus patients have antiphospholipid syndrome, which is characterized by the presence of aPL along with recurring blood clots, pregnancy complications, and other clinical features. Laboratory tests that identify aPL are:
The LAC is the most important of these antibodies because it confers the greatest risk for developing clinical complications. Of the subcomponents of aCL and aβ2GPI, IgG is associated with the greatest risk. As with other autoantibodies, strongly positive tests are much more important than are weakly positive ones. LAC may be reported as a ratio (1:3 is low positive, 1:5 or 1:6 is strong positive) or as seconds needed to form a clot, compared to normal done that day (if the normal is 28 seconds, 35 seconds and higher would be unequivocally positive and 60 seconds very strongly positive).
For aCL and aβ2GPI, using the standard international units, normal is usually 16 to 20, equivocal 21 to 40, positive 41 to 80, and high positive (greater than 80). Because a number of infections and injuries can cause temporarily positive antibodies that are not an indication of disease, a diagnosis of antiphospholipid syndrome usually requires that the antibody be present for at least 12 weeks (as indicated by a repeat positive test checked at least 12 weeks after the first).
If aPL are found in a patient who has no blood clots and is not pregnant, usually no treatment is warranted, though individual circumstances may suggest use of aspirin or hydroxychloroquine and sometimes other medications if risk of blood clot is high, for instance before a long airplane flight or surgery. If a patient has a blood clot or other signs of antiphospholipid syndrome, anticoagulants (blood-thinning medications) may be advised, potentially throughout the patient’s life.
Commercial laboratories sell panel tests, combining several of the above tests and sometimes other tests that are not routinely done, that these labs say give better information and more conveniently than do standard tests. As of this writing, however, there is no proof that these tests are beneficial, because false positives are common.
The tests below help to monitor disease activity and guide treatment. If the results are abnormal, further medical evaluation may be warranted to determine whether the abnormality is due to lupus, medications used to treat it, or some unrelated health problem.
The complement system is a series of proteins that assemble in domino fashion to destroy bacteria and viruses invading the body. The signal that initiates this domino cascade, or “activates” complement, is when an antibody meets an antigen (the bacterium or virus, when this occurs in the context of a healthy immune system protecting the body from harm). Because lupus autoantibodies initiate the same signal and activate complement despite the absence of an identified bacterium or virus, the measurement of complement proteins can be used to monitor lupus activity. It usually suffices to measure only two of the complement proteins, called C3 and C4. CH50, or total complement, is a blood test that measures all the complement proteins at once and may give additional information. CH50 is a much more complicated test, however, and is not routinely done.
Low C3 and C4 levels (below 60 for C3 and below 15 for C4 in the usual American measure), occur in active lupus, especially when the kidneys are affected or there is immune breakdown of blood cells (autoimmune hemolytic anemia, AIHA). Other manifestations of lupus, such as brain disease, do not cause low complement levels.
Low complement levels are not specific to lupus. They may be seen in other immune-system-mediated illnesses and in severe infections. About 10% of patients with lupus are born with abnormal complement components, especially C4, so their tests are always abnormal. Interpreted in context, C3 and C4 levels may reflect the activity of the disease. In most patients, recovery from lupus flare is indicated by the return of complement levels to normal. In an apparently well patient who usually has a normal complement level, a sudden decrease may signal an impending flare and the need for close physician follow-up. But a decrease in complement level does not itself warrant treatment, if no symptoms are present.
CBC provides information about the red blood cell (RBC), white blood cell (WBC), and platelet counts, and health of RBCs, all of which may be abnormal in lupus and may need treatment. Common issues are:
Erythrocyte sedimentation rate (ESR, also sometimes called simply "sedimentation rate" or "sed rate") is an indirect indicator of inflammation. The test measures the rate (in millimeters per hour) at which red blood cells (erythrocytes) settle to the bottom of a test tube of blood. If inflammation is present, these cells can stick together and settle more quickly than individual cells. A high ESR, if there are no other reasons for it to be high (such as infection), suggests that lupus is active. A low rate is reassuring. The test is simple but not indicative of any one specific disease, and it is subject to inaccuracy. Normal values may range from 0mm/hr to 20 mm/hr − or 0mm/hr to30 mm/hr, depending on the laboratory – and the interpretation also varies based on age, sex, and other factors.
CRP, like the ESR, is an indirect indication of inflammation, but is more specific in the detection of disease activity, since it is not affected by as many variables. Levels may be high in obese persons and in infection. A normal value is less than one milligram per deciliter (<1.0 mg/dL).
Confusingly, cardiologists use a measure called high-sensitivity CRP (hsCRP) to predict risk of heart disease. The hsCRP test is the same as a CRP test, but done differently. It is roughly 10 times more sensitive than is the standard CRP. A result flagged as “abnormal” may not be concerning in a patient known to have SLE or another autoimmune condition.
These laboratory tests look at liver, kidney, endocrine, and other functions:
A given laboratory value may have different implications depending on the patient’s presentation. For example, an elevated AST might suggest muscle inflammation, and an elevated LDH and bilirubin might suggest AIHA. As with all laboratory tests, accurate interpretation requires guidance from a physician or other healthcare professional with a complete understanding of the clinical context.
Because lupus patients are prone to kidney disease, urine tests are ordered on a regular basis. Urine tests are evaluated for:
It is important to note that:
Learn more information about the SLE Workshop at HSS, a free support and education group held monthly for people with lupus and their families and friends.
Monica Richey, MSN, ANP-BC/GNP
Nurse Coordinator, Mary Kirkland Center for Lupus Care
Nurse Coordinator, Cardiovascular Disease Prevention Program