PXD009578-1

PXD009578 is an original dataset announced via ProteomeXchange.

Title	Serum autoantibodies to the glutamate receptor delta 2 in paediatric opsoclonus myoclonus ataxia syndrome
Description	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.
HostingRepository	PRIDE
AnnounceDate	2018-07-30
AnnouncementXML	Submission_2018-07-30_07:59:16.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Georgina Berridge
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-04-23 08:21:47	ID requested
⏵ 1	2018-07-30 07:59:17	announced

Berridge G, Menassa DA, Moloney T, Waters PJ, Welding I, Thomsen S, Zuberi S, Fischer R, Aricescu AR, Pike M, Dale RC, Kessler B, Vincent A, Lim M, Irani SR, Lang B, 2 serum antibodies in pediatric opsoclonus myoclonus ataxia syndrome. Neurology, 91(8):e714-e723(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: Autoimmune

cerebellum

encephalitis

GluD2

immunotherapy

opsoclonus myoclonus ataxia syndrome (OMAS)

neuroblastoma

paraneoplastic;

Roman Fischer
contact affiliation	Target Discovery Institute, NDMRB, University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
lab head
Georgina Berridge
contact affiliation	University of Oxford
contact email	georgina.berridge@ndm.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD009578
     1. Label: PRIDE project
     2. Name: Serum autoantibodies to the glutamate receptor delta 2 in paediatric opsoclonus myoclonus ataxia syndrome