Autoantibody-mediated cytotoxicity in paediatric opsoclonus–myoclonus syndrome is dependent on ERK-1/2 phophorylation

•Autoantibodies in paediatric OMS bind to extracellular epitopes of cerebellar neurons•The surface-binding autoantibodies are able to induce phosphorylation of ERK-1/2.•Antibody-mediated ERK-1/2 phosphorylation in OMS correlates with neuronal cytotoxity.

Paediatric opsoclonus–myoclonus syndrome (OMS) is in 50% of the cases associated with a neuroblastoma as a paraneoplastic syndrome and is associated with surface-binding antibodies against cerebellar granular neurons (CGN). To evaluate possible pathogenic effects of these autoantibodies on CGN we examined their influence on the MAPKinase enzymes ERK-1/2 and p38 using flow cytometry and phospho-specific antibodies. OMS IgG but not IgG from neuroblastoma without OMS or healthy controls induced phosphorylation of ERK-1/2 in cerebellar granular neurons (p < 0.01). No effect on p38 phosphorylation or on HEK293 control cell line could be detected. IgG-mediated phosphorylation of ERK-1/2 was associated with an increased cytotoxicity of CGN, which could be blocked by ERK-1/2 pathway inhibitor U0126. We here show that IgG-mediated anti-neuronal cytotoxicity in OMS is mediated by ERK-1/2 phosphorylation in CGN.

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