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Maria del Pilar Martin, PhD; Petra D. Cravens, PhD; Ryan Winger, BSc; Bernd C. Kieseier, MD; Sabine Cepok, PhD; Todd N. Eagar, PhD; Scott S. Zamvil, MD, PhD; Martin S. Weber, MD; Elliot M. Frohman, MD, PhD; Betty K. Kleinschmidt-DeMasters, MD; Thomas J. Montine, MD, PhD; Bernhard Hemmer, MD; Christina M. Marra, MD; Olaf Stüve, MD, PhD

Arch Neurol. 2009;66(8):1016-1020.

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.

Main Outcome Measures  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.

Author Affiliations: Departments of Neurology (Drs Martin, Cravens, Eagar, Frohman, and Stüve and Mr Winger) and Immunology (Drs Eagar and Stüve), University of Texas Southwestern Medical Center at Dallas, and Neurology Section, Veterans Affairs North Texas Health Care System, Medical Service (Dr Stüve), Dallas; Department of Neurology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany (Dr Kieseier); Department of Neurology, Klinikum Rechts der Isar, Technische Universität München, München, Germany (Drs Cepok, Weber, and Hemmer); Department of Neurology, University of California, San Francisco (Drs Zamvil and Weber); Department of Pathology, University of Colorado, Denver (Dr Kleinschmidt-DeMasters); and Departments of Pathology (Dr Montine) and Neurology (Dr Marra), University of Washington, Seattle.

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