Depletion of B lymphocytes from cerebral perivascular spaces by rituximab.
BACKGROUND
Rituximab is a recombinant chimeric monoclonal antibody against CD20, a molecule expressed on cells of the B-cell lineage. A phase 2 clinical trial recently provided strong evidence of the beneficial effects of rituximab in patients with relapsing-remitting multiple sclerosis. We and other investigators previously demonstrated that rituximab therapy depletes B lymphocytes from peripheral blood and cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis.


OBJECTIVE
To determine the effect of rituximab on the presence of B cells in cerebral perivascular spaces. Design, Setting, and Patients Case report from a tertiary academic medical center. Cerebral white matter from autopsy material of a patient with gastrointestinal mantle-cell lymphoma who developed progressive multifocal leukoencephalopathy following rituximab therapy was evaluated by immunohistochemistry. Location-matched brain sections of patients with multiple sclerosis not treated with rituximab, patients without central nervous system disease, and patients with progressive multifocal leukoencephalopathy not associated with rituximab were used as controls.


METHODS
Assessment of the number of B lymphocytes in cerebral perivascular spaces in a patient with gastrointestinal mantle-cell lymphoma treated with rituximab, patients with multiple sclerosis, patients with progressive multifocal leukoencephalopathy not associated with rituximab, and healthy control subjects.


RESULTS
We were unable to detect B cells in cerebral perivascular spaces of the patient who developed progressive multifocal leukoencephalopathy following rituximab therapy 8 months after her last dose. In contrast, B cells were detectable in all control brain tissues.


CONCLUSIONS
To our knowledge, this is the first report to show B-lymphocyte depletion from brain tissue following rituximab therapy. A reduction in B-cell numbers may be an important contributing factor in the pathogenesis of central nervous system infections.
Martin
Maria del Pilar
Mdel P
Department of Neurology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
Cravens
Petra D
PD
Winger
Ryan
R
Kieseier
Bernd C
BC
Cepok
Sabine
S
Eagar
Todd N
TN
Zamvil
Scott S
SS
Weber
Martin S
MS
Frohman
Elliot M
EM
Kleinschmidt-Demasters
Betty K
BK
Montine
Thomas J
TJ
Hemmer
Bernhard
B
Marra
Christina M
CM
Stüve
Olaf
O
D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology*; D001479:Basal Ganglia / Q000187:drug effects / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000473:pathology; D004292:Dominance, Cerebral / Q000187:drug effects / Q000502:physiology; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced* / Q000473:pathology*; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology*; D009186:Myelin Sheath / Q000187:drug effects* / Q000473:pathology*; D009460:Neurologic Examination / Q000187:drug effects; D000069283:Rituximab; D016879:Salvage Therapy
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab