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Linda
has now looked at almost 2000 sera, and found antibodies to acetylcholine
receptors, voltage-gated calcium and potassium channels, and to two neuronal
antigens called Hu and Yo, in between 3 and 12 per 1000 samples. In the
textbooks the prevalence of the associated diseases, myasthenia gravis,
the Lambert Eaton myasthenic syndrome, acquired neuromyotonia, paraneoplastic
subacute sensory neuronopathy and cerebellar ataxia is very much lower.
For instance, MG is usually said to be present in about 1 per 10,000 of
individuals, and this is the most commonly diagnosed of these conditions.
Thus Linda's work questions whether these neuroimmunological diseases are
much more common in the elderly than previously thought.
However, we have to be careful, because it is possible that not all the antibodies that we detect are harmful. The assays that we use involve solubilised protein molecules. If the antibodies are directed against that part of the molecule that is usually hidden inside the cell, then they will not have any effect in the patient. So now we have to look more carefully at the "specificity" of the antibodies that we have detected in order to see whether they bind to the outside of the molecules, and whether they can really affect their function. This will require tissue culture studies. At the same time, Professor Sir John Grimley Evans (Professor of Clinical Geratology in Oxford) will look at the individuals' hospital notes to see whether there is any indication that they have developed the relevant neurological disease. Because of ethical considerations he will not be able to ask the patients directly, although that may be possible at a later stage.
The fact that these antibodies have been detected, assuming that at least some of them are pathogenic, is important because it means that clinicians, particularly GPs and geratologists, should be encouraged to think more carefully about the possibility of these conditions. A recent report in the literature indicated that elderly people with MG are sometimes misdiagnosed as having strokes.
In fact, one of the anti-AChR positive sera that we have identified
came from a woman with a "stroke", suggesting that this is one area where
there should be more careful consideration of antibody-mediated neurological
diseases. Linda will be finishing this project over the next few months,
but has been appointed as the Myasthenia Gravis/Muscular Dystrophy Group
Centre Research Assistant, and will therefore continue to work closely
with the MGA - hopefully for many years to come.
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