title: The effects of intrathecal rituximab on biomarkers in multiple sclerosis.
abstract: OBJECTIVE
  Clinical trials of IV-rituximab have proved successful. It is unclear whether intrathecal (IT)-rituximab is more efficacious at lower doses. We examine its effects on B-cell biomarkers.
  
  
  METHODS
  MS patients received IT-rituximab at 3 time-points. CSF and serum samples were obtained at up to 5 time-points (days 0, 7, 14, 56 and 112). Serum and CSF BAFF and CXCL13, and CSF kappa and lambda free light chains (FLC) were measured. Flow cytometry was performed, examining effects on lymphocytes, CD3-19+ and CD3-20+ cells.
  
  
  RESULTS
  CSF BAFF fell following rituximab (p=0.0091 absolute values, p=0.0284 change from baseline) whilst serum BAFF increased across time-points 1-4 (p=0.0005 absolute values, p=0.0017 change from baseline). There were significant reductions in CD20+ and CD19+ cells in blood from baseline (p<0.0001) but not in CSF. CSF kappa FLC levels significantly increased (p=0.0480).
  
  
  CONCLUSIONS
  BAFF levels fall in CSF but increase in serum following IT-rituximab. Rituximab appears to act peripherally with dramatic decreases in peripheral CD20+ and CD19+ cells. It is likely that CSF B-cell counts were too low to enable differences to be seen. The rapid reduction in B-cells suggests rituximab has immediate effects. The profound depletion of B-cells, despite low doses of rituximab, underlines rituximab's efficacy.
authors.affiliation: Blizard Institute, Queen Mary University, 4 Newark Street, London E1 2AT, England.
authors.forename: Joanne
authors.initials: J
authors.lastname: Topping
authors.affiliation: Blizard Institute, Queen Mary University, 4 Newark Street, London E1 2AT, England. Electronic address: ruth.dobson@qmul.ac.uk.
authors.forename: Ruth
authors.initials: R
authors.lastname: Dobson
authors.affiliation: First Pavlov State Medical University, Center for Molecular Medicine, Laboratory of Autoimmune Diagnostics, 6/8 Leo Tolstoy St, 197022 Saint Petersburg, Russia.
authors.forename: Sergey
authors.initials: S
authors.lastname: Lapin
authors.affiliation: Federal Almazov Medical Research Centre, Saint Petersburg, Russia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Maslyanskiy
authors.affiliation: F. Hoffmann-La Roche Ltd., Pharmaceuticals Division, Grenzacherstrasse, Basel, Switzerland.
authors.forename: Harald
authors.initials: H
authors.lastname: Kropshofer
authors.affiliation: F. Hoffmann-La Roche Ltd., Pharmaceuticals Division, Grenzacherstrasse, Basel, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Leppert
authors.affiliation: Blizard Institute, Queen Mary University, 4 Newark Street, London E1 2AT, England.
authors.forename: Gavin
authors.initials: G
authors.lastname: Giovannoni
authors.affiliation: MS Center (City Clinical Hospital 31), Saint Petersburg, Russia.
authors.forename: Evgeniy
authors.initials: E
authors.lastname: Evdoshenko
mesh_terms: D000328:Adult; D018941:Antigens, CD19 / Q000378:metabolism; D018951:Antigens, CD20 / Q000378:metabolism; D053264:B-Cell Activating Factor / Q000097:blood / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D054382:Chemokine CXCL13 / Q000097:blood / Q000134:cerebrospinal fluid; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000134:cerebrospinal fluid; D007146:Immunoglobulin lambda-Chains / Q000134:cerebrospinal fluid; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid; D007278:Injections, Spinal; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D000069283:Rituximab / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid; D016896:Treatment Outcome
chemical_list: D018941:Antigens, CD19; D018951:Antigens, CD20; D053264:B-Cell Activating Factor; D015415:Biomarkers; C000604811:CD19 molecule, human; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D007155:Immunologic Factors; C505719:TNFSF13B protein, human; D000069283:Rituximab
keywords: B-cells; BAFF; CD19+; CD20+; Intrathecal rituximab; biomarkers