|Antibodies Predict Development of Multiple Sclerosis|
By Melissa Lee Phillips|
Neuroscience for Kids Consultant
August 11, 2003
Your hands have begun to tingle. It's not all the time, but more often than not, they feel slightly numb, as if their blood supply has been cut off. You're exhausted all the time, too. No matter how much sleep you get, you remain tired. You can't concentrate and you can't remember simple things. One day, your vision blurs and you see double images. You go to your doctor, who recommends that you see a neurologist.
The neurologist performs a number of tests on you: she gives you a neurological exam, testing your senses, reflexes, and walking ability. She takes a magnetic resonance image (MRI) of your brain, and removes some cerebrospinal fluid for testing. When all the tests are in, she says that it's possible that you have multiple sclerosis (MS), but it's too soon to tell. You have many of the behavioral symptoms of MS. Your MRI shows that some of your myelin, the insulating fatty material that surrounds nerve fibers and allows them to conduct fast electrical pulses, has deteriorated. Your cerebrospinal fluid contains some antibodies -- proteins that your body makes to fight foreign molecules -- that are normally not found in healthy people, but are often seen in MS patients.
Although your doctor sees these symptoms, she cannot give you a definite diagnosis. Approximately 80% of people with your symptoms eventually develop MS, but 20% do not. You will have to wait to see if you have another attack of symptoms. A second episode could come a month from now, five years from now, or never.
The difficulty involved with diagnosing MS is a major frustration for patients and their physicians. Most of the symptoms seen in MS patients can be caused by other diseases. Many medications are available to treat MS, but because of unpleasant or even severe side effects, they usually are not prescribed. This diagnosis will not be given until the person has a second attack, and goes in for a second round of testing. The time between the first and second attacks is not only an uncertain and stressful time for the patient, but research suggests that this time period may represent an important window for starting treatment. Studies indicate that early treatment can lessen the immediate symptoms of an MS attack and minimize the long-term effects of the disease. The challenge, therefore, is for physicians to be able to diagnose MS earlier, so that treatment can begin earlier.
Medical researchers at the University of Innsbruck in Austria recently made a discovery that could lead to an earlier diagnosis of MS. Thomas Berger and his colleagues (New England Journal of Medicine, July 10, 2003) reported that the presence of two antibodies in the blood serum of possible MS patients could predict if and when these people would develop clinically definite MS.
Antibodies are produced by the immune system in response to foreign invaders. If a cold virus enters the body, for example, immune cells produce antibodies that attach themselves to the virus to mark it for destruction by other immune cells. Healthy people produce antibodies to molecules that come from outside the body only. In certain diseases, known as autoimmune diseases, antibodies are produced against tissues within the person's own body. Rheumatoid arthritis, for example, is an autoimmune disease in which antibodies attack connective tissues in the joints. These tissues are degraded and sometimes destroyed; this may cause joint pain. MS is also an autoimmune disease, but instead of producing antibodies against connective tissue, MS patients produce antibodies against myelin. Because the myelin sheath is essential for fast electrical conduction in nerves, its destruction contributes to the classic symptoms of MS. The interruption of electrical impulses from the limbs to the brain causes the numbness and tingling in these body parts. Difficulty walking and moving results from slow or halted signals from the brain. Blurred vision, a common first symptom of MS, is the effect of myelin loss along the optic nerve, the nerve that carries visual information from the eyes to the brain.
Berger studied 103 patients; all of these people had one initial neurological event that suggested they had MS. He took samples of their serum, the clear part of the blood left over when all cells and clotting proteins have been removed. He tested each patient's blood serum for antibodies to two different proteins: myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG). Both of these proteins are components of myelin. In healthy people, the immune system recognizes that myelin is a component of the body itself, and so immune cells do not produce antibodies that attack myelin. In some people, however, this is not the case. Berger found that 22 of his patients had both of these myelin antibodies in their blood. Neither antibody was present in 39 patients, and 42 patients had antibodies to MOG, but not to MBP.
The researchers' goal was to see if the presence or absence of these antibodies could predict if and when the patients had a second attack of MS symptoms. They found that it could: 95% of patients positive for both antibodies had a relapse, after an average of about seven months. Only 23% of patients with neither antibody had a second attack during the study, and if they did, it came at an average of almost four years later. The patients with only one antibody fell in between: 83% of them had a relapse, at an average of about one year later.
Antibodies are almost certainly involved in the demyelination that occurs in MS, but Berger and his coworkers point out that they can't be sure that the MOG and MBP antibodies are the ones that attack myelin. It is possible, instead, that some other antibodies are attacking myelin initially, and then MOG and MBP antibodies are actually produced in response to the degraded myelin. Whatever the mechanism, this study indicates that the presence of these antibodies can predict the likelihood of a second attack, and this information can help the physician arrive at a diagnosis of multiple sclerosis.
This is the first study to show a connection between these antibodies and the timing of an MS attack. Additional studies will be needed to confirm these results before doctors and counselors can begin to incorporate these findings in their patient care. But Berger and his coworkers believe that this work could be important for the care and counseling of people who might develop MS. Patients who have the antibodies in their blood would be counseled differently than those who don't. And, perhaps even more importantly, patients who are very likely to develop MS quickly might be placed on MS-regulating drugs sooner than patients who are less likely to develop the disease. This early treatment, many believe, could slow the disease enough to affect the long-term quality of life of people with MS.
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