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Two-thirds of stiff-man syndrome(SMS)patients harbor an autoantibody specific for a 64-kD species of glutamic acid decarboxylase(GAD),the rate- limiting enzyme in GABA synthesis.We assayed SMS antisera from two patients with SMS for the presence of anti-GAD antibodies using Western blot,immunohistochemical,and enzymatic analyses.Both SMS antisera recognized an 80-kD antigen present in human and rat neuronal extracts,and failed to recognize the 64-kD GAD species.Immunohistochemistry demonstrated neuronal binding identical to that reported with anti-GAD antibodies.Both sera depleted GAD activity from brain extracts.Our analysis indicates that these SMS antisera differ from previously reported SMS antisera by recognizing a novel 80-kD antigen,and suggests that they contain antibodies directed against either a species of GAD different in size from the 64-kD enzyme,or a protein that co-immunoprecipitates with GAD. |
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