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PO221 Pathological mechanisms of glycine receptor antibodies
  1. Sarah J Crisp1,
  2. John Rothwell1,
  3. Angela Vincent2,
  4. Dimitri M Kullmann1
  1. 1Institute of Neurology, University College London, UK
  2. 2University of Oxford, UK


Autoantibodies against glycine receptors (GlyRAbs) are found in half of patients with progressive encephalomyelitis with rigidity and myoclonus (PERM), and in patients with related acquired neurological syndromes (Carvajal-Gonzalez, 2014). The clinical features of PERM are consistent with disruption of spinal and brainstem inhibitory circuits. However, the presumed role of GlyRAbs in neurological disease is based largely on circumstantial clinical evidence. Using whole-cell patch-clamp we recorded spontaneous miniature glutamatergic and glycinergic postsynaptic currents from motoneurons in rat spinal cord cultures. We compared the currents in neurons incubated in IgG purified from patients with GlyRAbs or controls. IgG from patients selectively and severely disrupts glycinergic neurotransmission. Such disruption of inhibition in vivo would be consistent with many of the clinical features of PERM. Our electrophysiological findings therefore provide strong evidence that the antibodies in these cases are pathogenic. GlyRAbs internalise glycine receptors in HEK293 cells, but we find that they induce failure of glycinergic neurotransmission in neurons within 30 min at room temperature suggesting that they also directly antagonise glycine receptors. Alongside these investigations we are using clinical neurophysiology to identify affected circuits in GlyRAb patients. Findings are compared to patients with genetic defects in glycinergic pathways (hereditary hyperekplexia) and healthy controls.

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