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.