A novel antineuronal antibody in stiff-man syndrome

Darnell, Robert B. MD, PhD
Victor, Jonathan MD, PhD
Rubin, Michael MD, FRCP(C)
Clouston, Paul MBBS, FRACP
Plum, Fred MD

Department of Neurology and Neuroscience (Drs. Darnell, Victor, Rubin, Clouston, and Plum), The New York Hospital-Cornell Medical Center, and Memorial Sloan-Kettering Cancer Center (Dr. Darnell), Cornell University Medical College, New York, NY.

Address correspondence and reprint requests to Dr. Robert B. Darnell, Department of Molecular Neuro-Oncology, Rockefeller University, Box 226, 1230 York Avenue, New York, NY 10021.

Supported in part by PHS Research Grant #RR00047 from the General Research Center Branch, Division of Research Facilities and Resources, Bethesda, MD. R.B.D. is supported in part by a Clinical Investigator Development Award from the National Institutes of Health, grant NS01461-01, and J.V. by National Institutes of Health grants EY7977 and EY9314.

Received April 1, 1992. Accepted for publication in final form May 13, 1992.

Neurology 43(1):p 114-120, January 1993.

Article abstract

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.