title: Chemokine/cytokine profiling after rituximab: reciprocal expression of BCA-1/CXCL13 and BAFF in childhood OMS.
abstract: The aim of the study was to test the hypothesis that B-cell repopulation following rituximab (anti-CD20) therapy is orchestrated by chemokines and non-chemokine cytokines. Twenty-five children with opsoclonus-myoclonus syndrome (OMS) received rituximab with or without conventional agents. A comprehensive panel of 40 chemokines and other cytokines were measured in serum by ELISA and multiplexed fluorescent bead-based immunoassay. Serum BAFF concentration changed dramatically (even after first infusion) and inversely with B-cell depletion/repopulation and CXCL13 concentration at 1, 3, and 6 months. Negative correlations were found for BAFF concentration vs blood B cell percentage and serum CXCL13 concentration; positive correlations with serum rituximab concentrations. Six months after initiation of therapy, no significant difference in the levels of APRIL, CXCL10, IL-6, or 17 other cytokines/chemokines were detected. These data reveal a major role for BAFF in peripheral B cell repopulation following rituximab-induced B-cell depletion, and novel changes in CXCL13. ClinicalTrials.gov NCT0024436.
authors.affiliation: National Pediatric Myoclonus Center and Neuroimmunology Laboratory, Southern Illinois University School of Medicine, Springfield, IL 62794-9643, USA. mpranzatelli@siumed.edu
authors.forename: Michael R
authors.initials: MR
authors.lastname: Pranzatelli
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Tate
authors.forename: Anna L
authors.initials: AL
authors.lastname: Travelstead
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Verhulst
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D053264:B-Cell Activating Factor / Q000097:blood; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology; D054382:Chemokine CXCL13 / Q000097:blood; D018925:Chemokines / Q000097:blood*; D002648:Child; D016207:Cytokines / Q000097:blood*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007118:Immunoassay / Q000379:methods; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000627:therapeutic use; D007155:Immunologic Factors / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D053578:Opsoclonus-Myoclonus Syndrome / Q000097:blood* / Q000188:drug therapy*; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D053264:B-Cell Activating Factor; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D018925:Chemokines; D016207:Cytokines; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; C505719:TNFSF13B protein, human; D000069283:Rituximab; D000324:Adrenocorticotropic Hormone