Autoantibodies to a 128-kd synaptic protein in three women with the stiff-man syndrome and breast cancer

N Engl J Med. 1993 Feb 25;328(8):546-51. doi: 10.1056/NEJM199302253280805.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Animals
  • Autoantibodies / analysis*
  • Autoantibodies / blood
  • Autoantigens / immunology
  • Blotting, Western
  • Brain / immunology
  • Breast Neoplasms / complications*
  • Carcinoma, Intraductal, Noninfiltrating / complications*
  • Cerebrospinal Fluid / immunology
  • Female
  • Glutamate Decarboxylase / immunology
  • Humans
  • Immunoenzyme Techniques
  • Middle Aged
  • Nerve Tissue Proteins / immunology*
  • Paraneoplastic Syndromes
  • Precipitin Tests
  • Rats
  • Stiff-Person Syndrome / etiology
  • Stiff-Person Syndrome / immunology*
  • Synapses / immunology*


  • Autoantibodies
  • Autoantigens
  • Nerve Tissue Proteins
  • Glutamate Decarboxylase