Dataset Information

Serum autoantibodies to the glutamate receptor delta 2 in paediatric opsoclonus myoclonus ataxia syndrome

ABSTRACT: Abstract Objective: To identify neuronal surface antibodies in opsoclonus myoclonus ataxia syndrome (OMAS) with contemporary antigen discovery methodology. Methods: OMAS patient serum IgG immunohistochemistry using age-equivalent rat cerebellar tissue was followed by immunoprecipitation, gel electrophoresis and mass spectrometry generated a list of potential neuronal surface cerebellar autoantigens. Live cell-based assays (CBA) were used to confirm membrane-surface antigens and adsorb antigen-specific IgGs. The serological results were compared to the clinical data. Results: Four of the six OMAS sera tested bound rat cerebellar sections. Two of these sera with similar immunoreactivities against rat cerebellar sections were used in immunoprecipitation experiments using cerebellum from postnatal rat pups (P18). Mass spectrometry identified 12 cell-surface proteins, of which glutamate receptor delta 2 (GluD2), a predominately cerebellar-expressed protein, was found at a threefold higher concentration than the other 11 proteins. Antibodies to GluD2 were identified in 14/16 (87%) OMAS samples, compared with 5/139 (5%) pediatric and 1/38 (2.6%) adult serum controls (p<0.0001), and in 2/4 sera from patients with neuroblastoma without neurological features. Adsorption of positive OMAS sera against GluD2-transfected cells substantially reduced but did not eliminate, reactivity towards cerebellar sections. Conclusion: Autoantibodies to GluD2 are frequent in patients with OMAS, bind to surface determinants and are potentially pathogenic.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat) Homo Sapiens (human)

TISSUE(S): Brain, Dendritic Cell

DISEASE(S): Neuroblastoma

SUBMITTER: Georgina Berridge

LAB HEAD: Roman Fischer

PROVIDER: PXD009578 | Pride | 2018-07-30

REPOSITORIES: Pride

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Publications

Glutamate receptor δ2 serum antibodies in pediatric opsoclonus myoclonus ataxia syndrome.

Berridge Georgina G Menassa David A DA Moloney Teresa T Waters Patrick J PJ Welding Imogen I Thomsen Selina S Zuberi Sameer S Fischer Roman R Aricescu A Radu AR Pike Michael M Dale Russell C RC Kessler Benedikt B Vincent Angela A Lim Ming M Irani Sarosh R SR Lang Bethan B

Neurology 20180725 8

<h4>Objective</h4>To identify neuronal surface antibodies in opsoclonus myoclonus ataxia syndrome (OMAS) using contemporary antigen discovery methodology.<h4>Methods</h4>OMAS patient serum immunoglobulin G immunohistochemistry using age-equivalent rat cerebellar tissue was followed by immunoprecipitation, gel electrophoresis, and mass spectrometry. Data are available via ProteomeXchange (identifier PXD009578). This generated a list of potential neuronal surface cerebellar autoantigens. Live cell ...[more]

PMID: 30045961

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Dataset Information

Serum autoantibodies to the glutamate receptor delta 2 in paediatric opsoclonus myoclonus ataxia syndrome

Publications

Glutamate receptor δ2 serum antibodies in pediatric opsoclonus myoclonus ataxia syndrome.

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