B- and t-cell markers in opsoclonus-myoclonus syndrome: immunophenotyping of CSF lymphocytes

Abstract

Although an autoimmune etiology is likely, the pathophysiology of opsoclonus-myoclonus syndrome (OMS) remains poorly understood, and no immunologic abnormalities have correlated with neurologic severity. In addition, conventional immunotherapies often do not prevent relapse or permanent sequelae. In children, neuroblastoma and viral infections are the most common cause. The aim of this study was to test the cellular immune hypothesis of OMS in a cross-sectional study and determine if CSF lymphocyte subset analysis provides biomarkers of disease activity. The expression of lymphocyte surface antigens was investigated in CSF and blood of 36 children with OMS and 18 control subjects, using a comprehensive panel of monoclonal antibodies to adhesion and activation proteins in combination with anti-CD3 and anti-CD45 antibodies in 4-color fluorescence-activated cell sorting. Although most children with OMS had normal CSF cell counts, they exhibited expansion of CD19+ B-cell (up to 29%) and gamma/delta T-cell (up to 26%) subsets and a lower percentage of CD4+ T-cells and CD4/CD8 ratio, which persisted even years after disease onset and conventional treatments. The percentage of activated CSF T-cells was also higher. Abnormalities correlated with neurologic severity, as scored blinded from videotapes using a 12-item motor scale, and disease duration. No significant differences were found between tumor and no-tumor groups. In children with neuroblastoma, tumor resection or cancer chemotherapy did not alter immunologic abnormalities. The authors conclude that CSF B- and T-cell recruitment is linked to neurologic signs in pediatric OMS, which may relate to relapses and disease progression.—Valerie Biousse