Abstract
Introduction
Opsoclonus-myoclonus syndrome (OMS) is an autoimmune paraneoplastic disorder characterized by B and T cell abnormalities in cerebrospinal fluid (CSF) and propensity for relapse. The study aim was to assess whether rituximab-induced B cell ablation in CSF outlasts repopulation in blood and if there are changes in other lymphocyte subsets.
Materials and Methods
In 25 children with OMS, the expression of CSF and blood lymphocyte surface antigens was evaluated by flow cytometry before and at intervals after rituximab therapy.
Results
The reduction in CSF CD27+ memory, CD38+ activated, CD5+, and other B cell subsets was profound (p < 0.0001), comparable across groups (−94%), and sustained over 12–18 months despite repopulation in blood. The observed lag in memory B cell pool recovery in the CSF compared to peripheral blood may be clinically relevant. T cell phenotypic changes involved frequency, not absolute counts, and were transient. Co-treatment with IVIg or ACTH did not significantly alter B cell depletion or repletion.
Discussion
These data indicate that rituximab affords long-term protection against CSF B cell expansion in OMS (ClinicalTrials.gov NCT00244361).
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Acknowledgments
Supported by a clinical trial contract (study number U2743s) to M.R.P. from Genentech, Inc. (South San Francisco, CA)/Biogen IDEC (San Diego, CA) and by grants from the Spastic Paralysis and Allied Diseases of the Central Nervous System Research Foundation (Illinois-Eastern Iowa District Kiwanis International) and Questcor Pharmaceuticals, Inc. (Union City, CA, USA). The authors thank Jennifer A. Swan for dataset graphics, Tammy A. Boyd for typing the manuscript, and patients for providing samples for this analysis.
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Pranzatelli, M.R., Tate, E.D., Travelstead, A.L. et al. Long-Term Cerebrospinal Fluid and Blood Lymphocyte Dynamics After Rituximab for Pediatric Opsoclonus-Myoclonus. J Clin Immunol 30, 106–113 (2010). https://doi.org/10.1007/s10875-009-9335-3
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DOI: https://doi.org/10.1007/s10875-009-9335-3