Functional characterisation of autoantibodies from patients with pediatric opsoclonus–myoclonus-syndrome

Abstract

Paraneoplastic opsoclonus–myoclonus-syndrome (OMS) both in children and adults is suspected to be the result of an autoimmune response directed against cross-reactive proteins of tumor and neuronal cells. We here characterised the binding and functional activities of anti-neuroblastoma antibodies in IgG fractions from 11 OMS children with and without neuroblastoma. IgG fractions from neuroblastoma without OMS (NB) and healthy children served as controls. Indirect immunofluorescence and Western blot revealed IgG binding to intracellular autoantigens in all OMS patients, but in only one of the controls ( p < 0.001). Using flow cytometry, we could demonstrate surface binding of IgG fractions in all OMS patients, but only in one of control ( p < 0.001). Moreover OMS IgG exhibited a significant anti-proliferative and a cytotoxic effect on neuroblastoma cells compared to control IgG ( p < 0.001 and p < 0.01). TUNEL assay revealed increased apoptotic cell death of the neuroblastoma cells after exposure to OMS IgG, but not to NB or control IgG ( p < 0.01). Preabsorption of membrane binding abandoned the anti-proliferative effect of OMS IgG. These findings indicate that surface-binding autoantibodies are present in OMS patients and these autoantibodies cause inhibition of cell proliferation and induce apoptosis.