Discussion
In our case, multiple lymphoid follicles including abundant CD20-positive B cells in the tumor tissue of neuroblastoma[10], oligoclonal bands, anti-GluRδ2 antibodies and increased CD20-positive B cells in CSF[11] have been recognized, as previously reported. In addition, these findings in CSF declined in parallel with improvement of symptoms. Therefore, humoral immunity in CSF has been considered to contribute to the pathogenesis of OMS.[2] Based on humoral immunity pathogenesis theory, immunosuppressive therapies such as glucocorticoid and IVIg have been performed. However, the details of antibody-production mechanisms and the mechanisms underlying the effects of immunosuppressive strategies on OMS have yet to be elucidated.
Our study revealed that the most abundant B-cell clone in CSF, which has been reported to reflect the disease activity of OMS, also existed in tumor tissue as the most abundant clone. Since the dominant B-cell clone in microenvironment has been reported to reflect the existence of specific antigen targeted by specific humoral immune response [12,13], the low diversity of B-cell clones in CSF may suggest a specific humoral immune response to the central nervous system. Anti-GluRδ2 antibodies have also been reported to bind to cerebellar Purkinje cells.[3] Therefore, these findings may indicate that the B-cell clone sensitized in neuroblastoma tumor tissue migrates into the CSF and produces autoantibodies such as anti-GluRδ2 antibodies, contributing to the pathogenesis of OMS.
No pathogenesis-based treatment strategies for OMS have yet been established. However, considering that identical B-cell clone in CSF and tumor tissue contribute to the pathogenesis of OMS, rituximab may be a reasonable strategy to diminish identical B-cell clone. In the past, rituximab has been reported as a salvage therapy for refractory OMS patients showing no response to glucocorticoid and IVIg[14,15], however late administration of rituximab as salvage therapy has been reported as ineffective.[5] Recently, early administration of rituximab as the first-line treatment has been reported as an effective therapy against OMS.[6,16] It is conceivable that depletion of identical B-cell clone from both CSF and tumor tissue may lead to cure of OMS. Although our findings are based on a single case, early administration of rituximab might represent a reasonable strategy for OMS-NB.