Stiff person-syndrome IgG affects presynaptic GABAergic release mechanisms

The majority of patients with stiff person-syndrome (SPS) are characterized by autoantibodies to glutamate decarboxylase 65 (GAD65). In previous passive-transfer studies, SPS immunoglobulin G (IgG) induced SPS core symptoms. We here provide evidence that SPS-IgG causes a higher frequency of spontaneous vesicle fusions. Sustained GABAergic transmission and presynaptic GABAergic vesicle pool size remained unchanged. Since these findings cannot be attributed to anti-GAD65 autoantibodies alone, we propose that additional autoantibodies with so far undefined antigen specificity might affect presynaptic release mechanisms.