While passive transfer experiments have provided evidence for antibody mediated disturbance of excitatory synapses e.g. in myasthenia gravis or Lambert Eaton syndrome, disturbance of inhibitory synaptic transmission by antineuronal antibodies in- vivo remains to be shown (Sommer et al., 2005 Lancet 365, 1406). Intrathecal injection of IgG from a patient with anti- amphiphysin associated stiff person syndrome (SPS) induced symptoms of SPS in rats including stiffness, spasms, decreased motor activity and reduced exploration in the open field and elevated plus maze suggesting increased anxiety- and fear-related behaviour. Depletion of the anti-amphiphysin specific antibodies from the patient IgG by affinity chromatography abolished these findings.

Suppression of the H-reflex by conditioning stimuli was inhibited. Compared to control animals dorsal root potentials were reduced in treated rats after single and repetitive volleys, consistent with a defect in GABAergic presynaptic inhibition. Thus auto-antibodies can cause a disease of the central nervous system by blocking presynaptic inhibition.