title: Autoantibody-mediated cytotoxicity in paediatric opsoclonus-myoclonus syndrome is dependent on ERK-1/2 phophorylation.
abstract: 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.
authors.affiliation: Department of Neurology, Medical School, Justus-Liebig-University, Giessen, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Fühlhuber
authors.affiliation: Department of Neurology, Medical School, Justus-Liebig-University, Giessen, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Bick
authors.affiliation: Department of Neurology, Medical School, Justus-Liebig-University, Giessen, Germany.
authors.forename: Marlene
authors.initials: M
authors.lastname: Tschernatsch
authors.affiliation: Department of Neurology, Medical School, Justus-Liebig-University, Giessen, Germany.
authors.forename: Backialakshmi
authors.initials: B
authors.lastname: Dharmalingam
authors.affiliation: Department of Neurology, Medical School, Justus-Liebig-University, Giessen, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Kaps
authors.affiliation: Department of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany.
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Preissner
authors.affiliation: Department of Neurology, Medical School, Justus-Liebig-University, Giessen, Germany; Department of Neurology, Gummersbach Hospital, Gummersbach, Germany. Electronic address: franz.blaes@neuro.med.uni-giessen.de.
authors.forename: Franz
authors.initials: F
authors.lastname: Blaes
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology* / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D002531:Cerebellum / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology* / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D053578:Opsoclonus-Myoclonus Syndrome / Q000276:immunology* / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; D007770:L-Lactate Dehydrogenase; D020928:Mitogen-Activated Protein Kinases
keywords: Autoantibodies; Neuroblastoma; Opsoclonus-myoclonus syndrome; Paraneoplastic neurological syndrome