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Previous Volume 328:546-551 February 25, 1993 Number 8 Next

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ABSTRACT

Background The stiff-man syndrome is a rare disease of the central nervous system characterized by progressive rigidity of the body musculature. Autoantibodies directed against glutamic acid decarboxylase are present in about 60 percent of patients with the syndrome. In this group, there is a striking association of the stiff-man syndrome with organ-specific autoimmune diseases, primarily insulin-dependent diabetes mellitus.

Methods We studied three women with the stiff-man syndrome and breast cancer, seeking autoantibodies directed against nervous system antigens in serum and cerebrospinal fluid by immunocytochemical techniques, Western blotting, and immunoprecipitation.

Results Autoantibodies directed against a 128-kd brain protein were found in two of the women with the stiff-man syndrome and breast cancer. These results led to a search for breast cancer in the third patient with the stiff-man syndrome, who also had autoantibodies. A small invasive ductal carcinoma was detected by ultrasonography and removed. Serum samples from all three patients were negative for autoantibodies directed against glutamic acid decarboxylase. Autoantibodies against the 128-kd antigen were not detected in control patients with the stiff-man syndrome without breast cancer or in patients with cancer who did not have the syndrome. Within the nervous system, the 128-kd autoantigen was localized in neurons and concentrated at synapses.

Conclusions In a subgroup of patients with the stiff-man syndrome, the condition is likely to have an autoimmune paraneoplastic origin. The detection of autoantibodies against the 128-kd antigen in patients with this syndrome should be considered an indication to search for an occult breast cancer.

Source Information

From the Departments of Cell Biology (F.F., M.S., P.D.C.) and Pathology (G.T.), and Howard Hughes Medical Institute (R.C., P.D.C.), Yale University School of Medicine, New Haven, Conn.; Istituto di Semeiotica Medica, Universita di Padova, Padua, Italy (M.A.); Divisione Neurologica, Ospedale di Belluno, Belluno, Italy (G.F.); the Department of Neurology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom (D.B., N.C.); the Department of Immunology, London Hospital Medical College, London (G.F.B.); and Istituto Neurologico Mondino, Universita di Pavia, Pavia, Italy (G.P.).

Address reprint requests to Dr. De Camilli at Howard Hughes Medical Institute, Department of Cell Biology, Boyer Center for Molecular Medicine, 295 Congress Ave., New Haven, CT 06510.

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