Antibodies against glutamic acid decarboxylase: prevalence in neurologicaldiseases

High prevalence of autoantibodies against glutamic acid decarboxylase (GAD- Ab) in stiff man syndrome (SMS) not only helps diagnosis, but also suggests immune mediated impairment of GABAergic functions. However, the presence o f GAD-Ab has also been reported in other neurological syndromes. Therefore the prevalence of GAD-Ab was investigated in SIMS, progressive encephalomye litis with rigidity and myoclonus (PERM), and in other neurological disease s (OND). Serum antibodies against the GAD isoforms, GAD65 and GAD67, were i nvestigated with radioimmunoassays in 13 patients with SIMS, nine with PERM , 279 consecutive patients with OND, and in 100 normal controls. Results-Prevalence of GAD65Ab was around 80% in patients with SMS/PERM comp ared with 5% in patients with OND and 1% in normal controls. Prevalence of GAD67Ab was 60% in SMS/PERM, 2% in patients with OND, and 1% in normal cont rols. Raised GAD-Ab clustered in an OND subgroup with sporadic progressive ataxia, but not in OND subgroups with recognised neuroimmunological disease s. In conclusion, increased GAD-AE, is neither a non-specific epiphenomenon of neuronal damage nor a common feature of recognised neuroimmunological d isorders. In neurological diseases, GAD-Ab may be a pathogenetic agent or a marker for an ongoing autoimmune process, or both.