Long-term cerebrospinal fluid and blood lymphocyte dynamics after rituximab for pediatric opsoclonus-myoclonus.
BACKGROUND
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.


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.


CONCLUSIONS
These data indicate that rituximab affords long-term protection against CSF B cell expansion in OMS (ClinicalTrials.gov NCT00244361).
National Pediatric Myoclonus Center, Southern Illinois University School of Medicine, Springfield, IL, USA. mpranzatelli@siumed.edu
Michael R
MR
Pranzatelli
Elizabeth D
ED
Tate
Anna L
AL
Travelstead
Jerry A
JA
Colliver
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D016130:Immunophenotyping; D007223:Infant; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D053578:Opsoclonus-Myoclonus Syndrome / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000069283:Rituximab; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D000069283:Rituximab