LEARNING ABOUT LUPUS: Laboratory Tests in Lupus

LEARNING ABOUT LUPUS: A USER FRIENDLY GUIDE
From the Lupus Foundation of Delaware Valley, Inc.
Edited by: Mary E. Moore, Ph.D., M.D., Carolyn H. McGrory, MS, RN, Robert S. Rosenthal, M.D.
Laboratory Tests in Lupus
Burton Zweiman, MD

Most physicians with a lot of experience in the care of lupus patients can make the diagnosis of systemic lupus erythematosus based upon certain symptoms and findings when they take a medical history and do a physical examination. Sometimes, however, these physical symptoms or clinical clues are not well defined early in the course of lupus and, therefore, certain laboratory tests are useful in making the diagnosis.

Many people ask, "is there a laboratory test that can diagnose lupus in all patients?" Despite much research in this area, the answer must still be "No". There is no one test which can do this. The laboratory test performed most often is the immunofluorescence test for antinuclear antibodies (ANA). This is often simply called the ANA test. It has almost entirely replaced the older LE cell test which is more time consuming to perform and is less accurate. The ANA test is a very sensitive one. Over ninety-five percent of untreated lupus patients have high ANA levels in their blood.

A small number of individuals have an unusual lupus disorder with a negative ANA test, a rash and a high sensitivity to sunlight. For most people, however, an ANA test with negative results in several repeated tests performed in a good laboratory is strong evidence against the diagnosis of systemic lupus. The ANA test is not specific for lupus. This means that people with other diseases can also have a high ANA. Elevated blood ANA levels are found in a number of other disorders including some with symptoms similar to lupus. Sometimes this leads to confusion and a diagnosis of lupus is made in someone with another disorder just because the ANA test is abnormal. Much research has been done to expand and refine the ANA test in order to help find a test more specific for lupus. Although the ANA levels in the blood are generally higher in untreated lupus patients than in patients with other diseases, this is not always so.

A diagnosis of lupus, therefore, cannot be made only on the basis of a high ANA. It is helpful to know in diagnosing lupus that the ANA is actually a group of antibodies directed against different parts of cells within our bodies. in laboratories with special equipment, these antibodies can now be detected individually. Some of these individual antibodies are very specific for the diagnosis of lupus. Some of these are listed below:

Anti-ds (double-stranded) DNA antibodies. These are substances which react to the material which makes up the genes found in cells. Double stranded DNA also plays a key role in the growth and multiplication of these cells. increased blood levels of antidsDNA antibodies are found in about 70% of lupus patients, and found very infrequently in other disorders. However, the dsDNA used in the test must be prepared very carefully so that it does not contain single stranded DNA. Antibodies against this single stranded DNA are commonly found in disorders other than lupus, and can confuse the results of the test. Anti-dsDNA antibodies are more commonly found in lupus patients whose disease is active, particularly when the disease involves the kidneys or the central nervous system.

Anti-Sm (Smith) antibodies. These antibodies are named after the patient, a person named Smith, in whom they were first found. They react with another part of the cell nucleus, the central part of the cell, and are found in about 30% of lupus patients. Anti-Sm antibodies are found very rarely in disorders other than lupus.

Anti-Ro (or SS-A) antibodies. These are found in some lupus patients, particularly those with a certain type of sun-sensitivity rash. If a pregnant lupus patient has anti-Ro antibodies, it is more likely that her baby will have a certain type of congenital heart disorder.

Anti-Ro antibodies are also found in a disorder called Sjogren's syndrome. Sometimes lupus can occur together with Sjogren's syndrome. Antihistone antibodies. These antibodies are found in the blood of many lupus patients and are directed against a protein which is frequently attached to the DNA (the material of which genes are made) within the cell nucleus. These antibodies are of particular interest because they are also found in the blood of some people who have high ANA tests caused by taking certain medications. Recent evidence suggests that the antibodies in lupus patients react with different histones than do the antibodies in these individuals with high ANA tests related to medications.

Anti-RNP (ribonucleoprotein) antibodies. These antibodies occur commonly in lupus and some other disorders. Certain individuals (mainly women) develop a group of symptoms that do not point strongly to lupus or to one of the other connective tissue inflammatory diseases, but rather to a combination of several of these diseases. This has been called "mixed connective tissue disease" or "overlap syndrome". Anti-RNP antibody levels are often very high in this disorder.
Several other antibody tests are often performed when trying to make a diagnosis of lupus because they help tell the difference between lupus and certain other diseases. Antiscleroderma 70 (Scl70) antibody is found in one form of scleroderma. Anticentromere antibodies are found in another form of scleroderma. Anti-PM-1 and anti-Jo-1 antibodies are found in poliomyelitis. Rheumatoid factor (RF) is often found in the blood of patients with rheumatoid arthritis, a condition which can sometimes be confused with lupus.

Rheumatoid factor may also be found in the blood of about 20% of lupus patients, and in a number of other disorders. The levels of certain non-antibody proteins in the blood, called complement components, may be low in lupus patients, particularly when the disease is active. Low complement levels are not very helpful in diagnosing lupus, however, because they can be found in other diseases as well. Complement levels are more useful both in following the disease activity and the response to treatment of individual lupus patients. There are many laboratory tests which measure and identify whether or not specific organ systems are affected by luptis. These can be very valuable in the care of the individual lupus patient.

These will be discussed in other chapters dealing with involvement of individual organ systems in lupus but several examples are described briefly here.Kidney involvement in lupus can be determined by measuring the amount of protein found in the urine during a 24 hour period. The 24 hour urine collection can also be used to find out if there is any decrease in the filtering function of the kidneys and to check for growth of bacteria if an infection of the urinary tract is suspected. If enough bacteria grow when the urine is cultured, these bacteria can also be tested to help determine the best way to treat the infection.

In certain situations it may be necessary to perform a kidney biopsy to find out what type of involvement of the kidney is present. This involves inserting a needle into the kidney under local anesthesia (somewhat like having your jaw numbed to have dental work performed). One or more small pieces of kidney tissue are removed and looked at under the microscope.

Involvement of the central nervous system occurs commonly in lupus, but is often difficult to diagnose. The cerebrospinal fluid, (fluid which is present around the spinal cord and the brain), is abnormal in about 50% of those patients with central nervous system involvement in lupus. X-rays and magnetic resonance imaging (MRI) signals are now also being used to help diagnose involvement of the nervous system in lupus. Other blood tests can also be helpful for lupus patients. Anemia or a low blood count is frequently the result of disease activity. Levels in the blood of leukocytes (white blood cells), and platelets (small blood cells which are part of the clotting mechanism) may also be lower in active lupus. This happens so often that these particular abnormal findings are considered one of the criteria on which the diagnosis of lupus is based. Occasionally the platelet count is so low that a bleeding and bruising tendency may be present. In some individuals with lupus, there are abnormal blood proteins that appear to be antibodies against something in the platelets.

Platelets are involved in normal blood clotting. When these abnormal proteins are present certain blood clotting tests are abnormal (a lupus anticoagulant is detected) or the test for an antibody (anticardiolipin) is positive. What is surprising is that individuals with these antibodies do not have a bleeding tendency.

If anything, there is a tendency to develop blood clots. Women with these antibodies may have spontaneous abortions (miscarriages) if they become pregnant. This is discussed in more detail in Chapter 18 on Lupus and Pregnancy. These antibodies can also result in a false positive test for syphilis. An individual with such antibodies who is tested for syphilis when applying for a marriage license or job, or during routine admission to the hospital, may be told that the test is positive even though they do not in fact have syphilis. The reason for this is that these antibodies against platelets closely resemble the antibody that produces the positive test for syphilis.

Even though these patients do not have syphilis, their blood reacts to the test. Fortunately, this false-positive test can now be distinguished from a true-positive test for syphilis by another, more specific test for syphilis. If a person has repeated normal results using current very sensitive ANA blood tests, this is very strong evidence against a diagnosis of lupus. There is no test which is as specific for lupus as we would like. Results obtained from a group of tests can help the experienced physician distinguish lupus from other conditions with similar symptoms. In some ways they can also help to measure the response to treatment and whether or not disease activity is increasing.

Repeated measurements of certain blood tests may also help determine whether problems with the lupus patient or the fetus are developing during pregnancy. Intensive research is leading to new tests of the immune system. Hopefully, these will lead to easier diagnoses and improved treatment.

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This information is for "informational purposes" and is not meant to be used for medical diagnosis. Always consult your physician on matters such as this.