Data from: Glutamate receptor delta2 serum antibodies in paediatric opsoclonus myoclonus ataxia syndrome

Objective: To identify neuronal surface antibodies in opsoclonus myoclonus ataxia syndrome (OMAS) usingcontemporary antigen discovery methodology.
Methods: OMAS patient serum IgG 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-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 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.