HETEROGENEITY OF AUTOANTIBODIES IN STIFF-MAN SYNDROME

Stiff-man syndrome is a rare neurological disorder characterized by sk eletal muscle rigidity and spasms in which detection of circulating an ti-glutamic acid decarboxylase antibodies has suggested an autoimmune pathogenesis. To further define the role of autoimmunity in the pathog enesis, we studied anti-glutamic acid decarboxylase antibodies, as wel l 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 freq uency in the patients with stiff-man syndrome (61%) and those with oth er neurological disorders (65%). Islet-cell autoantibodies and anti-gl utamic acid decarboxylase antibodies were more common in stiff-man syn drome patients (38% and 31%) compared to the patients with other neuro logical disorders (6% and 3%, respectively; p < 0.001). With the excep tion of 1 patient in the other neurological disorders group, anti-glut amic acid decarboxylase antibodies were always associated with islet-c ell autoantibodies. Four patients with stiff-man syndrome had an assoc iated solid tumor: 3 of them had antibodies recognizing a 125/130-kd p rotein and not glutamic acid decarboxylase. Our study indicates that w ith immunological markers, patients with stiff-man syndrome can be sub divided into three groups: (1) patients with circulating islet-cell au toantibodies, anti-glutamic acid decarboxylase as well as other organ- specific autoantibodies, and the frequent association with an autoimmu ne disease (autoimmune variant); (2) patients with associated neoplasm s and circulating non-organ-specific autoantibodies but neither islet- cell nor anti-glutamic acid decarboxylase autoantibodies (paraneoplast ic variant); and (3) patients with no evidence of any known autoantibo dy or association with other clinically evident diseases (idiopathic v ariant). We conclude that the presence of anti-glutamic acid decarboxy lase antibodies is restricted to a subgroup of stiff-man syndrome pati ents with associated autoimmune diseases. The absence of these antibod ies does not exclude a diagnosis of stiff-man syndrome, which is still based on clinical and neurophysiological evidence.