Heterogeneity of autoantibodies in stiff-man syndrome

Stiff‐man syndrome is a rare neurological disorder characterized by skeletal muscle rigidity and spasms in which detection of circulating anti–glutamic acid decarboxylase antibodies has suggested an autoimmune pathogenesis. To further define the role of autoimmunity in the pathogenesis, we studied anti–glutamic acid decarboxylase antibodies, as well as organ‐ and non–organ‐specific autoantibodies in 13 patients with stiff‐man syndrome and 127 patients with other neurological disorders. Thyrogastric antibodies were more frequent in patients with stiff‐man syndrome (46%) than in those with other neurological disorders (12%) (p < 0.05). Non–organ‐specific antibodies were found at a similar frequency in the patients with stiff‐man syndrome (61%) and those with other neurological disorders (65%). Islet‐cell autoantibodies and anti–glutamic acid decarboxylase antibodies were more common in stiff‐man syndrome patients (38% and 31%) compared to the patients with other neurological disorders (6% and 3%, respectively; p < 0.001). With the exception of 1 patient in the other neurological disorders group, anti–glutamic acid decarboxylase antibodies were always associated with islet‐cell autoantibodies. Four patients with stiff‐man syndrome had an associated solid tumor: 3 of them had antibodies recognizing a 125/130‐kd protein and not glutamic acid decarboxylase. Our study indicates that with immunological markers, patients with stiff‐man syndrome can be subdivided into three groups: (1) patients with circulating islet‐cell autoantibodies, anti–glutamic acid decarboxylase as well as other organ‐specific autoantibodies, and the frequent association with an autoimmune disease (autoimmune variant); (2) patients with associated neoplasms and circulating non‐organ‐specific autoantibodies but neither islet‐cell nor anti–glutamic acid decarboxylase autoantibodies (paraneoplastic variant); and (3) patients with no evidence of any known autoantibody or association with other clinically evident diseases (idiopathic variant). We conclude that the presence of anti–glutamic acid decarboxylase antibodies is restricted to a subgroup of stiff‐man syndrome patients with associated autoimmune diseases. The absence of these antibodies does not exclude a diagnosis of stiff‐man syndrome, which is still based on clinical and neurophysiological evidence.