自己免疫性自律神経節障害(AAG)の病態と免疫療法

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Autoimmune autonomic ganglionopathy (AAG) is a disorder of isolated autonomic failure associated with antibodies to the nitotinic acetylcholine receptor of the autonomic ganglia resulting in severe orthostatic intolerance, syncope, constipation, gastroparesis, urinary retention, dry mouth, dry eyes, blurred vision and anhidrosis. The disorder is associated with and most likely caused by antibodies to gAChR. Antibodies to the gAChR are found in the serum of 50% of patients with the acute or subacute form of AAG, correlate to disease severity, and have been shown to pathogenic. In this study, we attempted to develop a novel technique to detect antibodies that bind to gAChR. We established a simple in vitro system termed GLIP (gaussia luciferase-reporter immunoprecipitation), which can detect protein-protein interactions with high sensitivity without using radioisotopes. Using this new method, we extensively reviewed the case histories with current clinical and laboratory evaluations that include testing for antibodies to a3 and b4 subunits of gAChR in serum available from the time of symptom onset. Here, we describe 7 patients with gAChR autoantibody and autonomic dysfunction. Our observations also suggest that autoimmune-mediated impairment of autonomic function may be partially reversible. Six of the 7 patients, except for case 6, improved in response to immunotherapy (e.g. PP, IVMP, IVIg, and immunosuppressant drugs) with symptomatic therapy. In our patients, improvement in neurological deficits occurred with treatment with considerable heterogeneity in the pattern of response. We interpreted the improvement in clinical symptoms correlated with the decrease in the levels of anti gAChR antibodies in each case. Some patients with seropositive AAG respond to treatment with IVMP, PP or IVIg, although when used as a single agent, subsequent treatments are required in patients to maintain the improvement. Previous anecdotal observations suggest that IVIg, PP, and a combined therapy might be efficacious in treating AAG. The more severely affect patients who did not respond to IVMP or PP monotherapy did benefit from combined therapy adding other first line therapy and immunosuppressant agents (prednisolone, tacrolimus, and azathioprine) and seemed to require prolonged immunotherapy for sustained clinical improvement in this study. These results suggest ongoing antibody production, not self-limited.
2013-10-31

自己免疫性自律神経節障害(AAG)の病態と免疫療法

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