Experience with IVIg in the treatment of patients with myasthenia gravis
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Neurology 1997;48(Suppl 5):S64-S69
Myasthenia gravis (MG) is the prototypic autoimmune disease for a number of reasons. (a) The antigen, the acetylcholine receptor (AChR), is known. (b) Antibodies against the AChRs can be detected and measured in patients' serum. (c) The patients' IgG binds to the AChRs at the postsynaptic region and, by fixing complement or crosslinking, results in internalization or degradation of the AChRs and simplification of the postsynaptic junctional folds. (d) The IgG antibodies are pathogenic because they transmit the disease to experimental animals and cause destruction of the AChRs in cultured myotubes. (e) Immunization of healthy animals with AChRs leads to MG that can be subsequently passed to other animals with purified IgG. (f) Removal of the pathogenic autoantibodies results in clinical improvement. [1-4]
Although MG is no longer "gravis" because it responds fairly well to the available therapies, we still do not have a cure for the disease. Treatment begins with anticholinesterases, which are helpful early in the disease, followed by thymectomy, performed in patients above puberty and below the age of 60 years. Therapy continues as needed and for long periods with the administration of steroids or various immunosuppressive therapies including azathioprine, cyclosporine and, periodically, plasmapheresis. [1-4] Given the chronicity of the disease, the long-term use of these therapeutic modalities needs to be curtailed because of their cumulative adverse side effects. The need for another effective immunomodulating therapy without long-term side effects has prompted experimentation with high-dose IVIg, an immunomodulating drug that is expensive but relatively safe compared to the other therapies. Considering the multiple mechanisms of action of IVIg in modifying the immune response, as discussed later, this drug may be a promising modality in the treatment of certain patients with MG at a given state of their illness.
I review here the present knowledge …
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