Autoantibodies to a 128-kd Synaptic Protein in Three Women with the Stiff-Man Syndrome and Breast Cancer

Franco Folli, Michele Solimena, Roxanne Cofiell, Mario Austoni, Giovanni Tallini, Giuliano Fasseta, David Bates, Niall Cartlidge, Gian Franco Bottazzo, Giovanni Piccolo, Pietro de Camilli

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248 Scopus citations

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., The stiff-man syndrome is a rare disorder of the central nervous system characterized by fluctuating but progressive muscle rigidity and spasms1,2. Sixty percent of the patients with this syndrome have autoantibodies directed against glutamic acid decarboxylase,36 an enzyme present both in neurons secreting g-aminobutyric acid and in pancreatic beta cells7,8. Glutamic acid decarboxylase autoantibodies are also found in patients with insulin-dependent diabetes mellitus9. Patients with the stiff-man syndrome who have such autoantibodies often have organ-specific autoimmune diseases, in particular insulin-dependent diabetes mellitus3,6. The absence of glutamic acid decarboxylase autoantibodies in 40 percent…

Original languageEnglish (US)
Pages (from-to)546-551
Number of pages6
JournalNew England Journal of Medicine
Volume328
Issue number8
DOIs
StatePublished - Feb 25 1993

ASJC Scopus subject areas

  • Medicine(all)

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