CSF B-cell expansion in opsoclonus-myoclonus syndrome: a biomarker of disease activity.
Lack of a biomarker of disease activity has hindered the therapy of childhood opsoclonus-myoclonus syndrome (OMS), which is purported to be mediated humorally. To determine if the cerebrospinal fluid (CSF) B lymphocyte, which may traffic into the central nervous system (CNS) to produce antibody locally, is one such biomarker, B lymphocytes were immunophenotyped in the CSF and blood of 56 children with OMS and 26 pediatric controls by dual-laser flow cytometry. Neurological severity was rated blindly from videotapes using a validated 12-item motor evaluation scale. Children with OMS manifested a 4- to 7-fold higher percentage of total B-cells in CSF (P < 0.0001), including CD5(+) (P = 0.001) and CD5(-) (P = 0.0004) B-cell subsets, compared with controls, in whom the percentages were negligible and unchanging with age. CSF expansion of both B-cell subsets increased with disease severity and decreased with disease duration (P </= 0.0001, ANOVA). Previous treatment with conventional immunotherapies, chemotherapy, or tumor resection had not normalized B-cell percentages in those with lingering symptoms. These studies reveal that CSF B-cell expansion in OMS is characteristic and often persistent. Presence of the autoreactive CD5(+) B-cell subset and correlations with neurological severity and disease duration suggest CSF B-cell expansion is a biomarker of disease activity and possible target for B-cell-specific therapy. Immunophenotyping of CSF lymphocytes by flow cytometry yields valuable clinical information missed by routine studies and allows crucial treatment decisions to be made rapidly.
Pranzatelli
Michael R
MR
Department of Neurology, Southern Illinois University School of Medicine, Springfield, Illinois, USA.|Department of Pediatrics, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
Travelstead
Anna L
AL
Department of Medical Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
Tate
Elizabeth D
ED
Department of Neurology, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
Allison
Tyler J
TJ
Department of Neurology, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
Verhulst
Steven J
SJ
Statistics and Research Consulting, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
D000293:Adolescent; D018941:Antigens, CD19 / Q000134:cerebrospinal fluid* / Q000276:immunology*; D001402:B-Lymphocytes; D015415:Biomarkers; D001932:Brain Neoplasms / Q000150:complications; D018956:CD5 Antigens / Q000134:cerebrospinal fluid* / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D016131:Lymphocyte Subsets; D008297:Male; D009447:Neuroblastoma / Q000150:complications; D020361:Paraneoplastic Syndromes, Nervous System / Q000134:cerebrospinal fluid* / Q000150:complications / Q000276:immunology*; D012720:Severity of Illness Index; D014743:Videotape Recording
D018941:Antigens, CD19; D015415:Biomarkers; D018956:CD5 Antigens