Depletion of B lymphocytes from cerebral perivascular spaces by rituximab

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

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Abstract

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. Locationmatched 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:Wewere 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.

Original languageEnglish (US)
Pages (from-to)1016-1020
Number of pages5
JournalArchives of Neurology
Volume66
Issue number8
DOIs
StatePublished - Aug 2009

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B-Lymphocytes
Progressive Multifocal Leukoencephalopathy
Mantle-Cell Lymphoma
Relapsing-Remitting Multiple Sclerosis
Multiple Sclerosis
Brain
Rituximab
Outcome Assessment (Health Care)
Lymphocyte Depletion
Central Nervous System Infections
Cells
Central Nervous System Diseases
Cell Lineage
Therapeutics
Cerebrospinal Fluid
Autopsy
Healthy Volunteers
Cell Count
Immunohistochemistry
Monoclonal Antibodies

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Martin, M. D. P., Cravens, P. D., Winger, R., Kieseier, B. C., Cepok, S., Eagar, T. N., ... Stuve, O. (2009). Depletion of B lymphocytes from cerebral perivascular spaces by rituximab. Archives of Neurology, 66(8), 1016-1020. https://doi.org/10.1001/archneurol.2009.157

Depletion of B lymphocytes from cerebral perivascular spaces by rituximab. / Martin, Maria Del Pilar; Cravens, Petra D.; Winger, Ryan; Kieseier, Bernd C.; Cepok, Sabine; Eagar, Todd N.; Zamvil, Scott S.; Weber, Martin S.; Frohman, Elliot; Kleinschmidt-DeMasters, Betty K.; Montine, Thomas J.; Hemmer, Bernhard; Marra, Christina M.; Stuve, Olaf.

In: Archives of Neurology, Vol. 66, No. 8, 08.2009, p. 1016-1020.

Research output: Contribution to journalArticle

Martin, MDP, Cravens, PD, Winger, R, Kieseier, BC, Cepok, S, Eagar, TN, Zamvil, SS, Weber, MS, Frohman, E, Kleinschmidt-DeMasters, BK, Montine, TJ, Hemmer, B, Marra, CM & Stuve, O 2009, 'Depletion of B lymphocytes from cerebral perivascular spaces by rituximab', Archives of Neurology, vol. 66, no. 8, pp. 1016-1020. https://doi.org/10.1001/archneurol.2009.157
Martin MDP, Cravens PD, Winger R, Kieseier BC, Cepok S, Eagar TN et al. Depletion of B lymphocytes from cerebral perivascular spaces by rituximab. Archives of Neurology. 2009 Aug;66(8):1016-1020. https://doi.org/10.1001/archneurol.2009.157
Martin, Maria Del Pilar ; Cravens, Petra D. ; Winger, Ryan ; Kieseier, Bernd C. ; Cepok, Sabine ; Eagar, Todd N. ; Zamvil, Scott S. ; Weber, Martin S. ; Frohman, Elliot ; Kleinschmidt-DeMasters, Betty K. ; Montine, Thomas J. ; Hemmer, Bernhard ; Marra, Christina M. ; Stuve, Olaf. / Depletion of B lymphocytes from cerebral perivascular spaces by rituximab. In: Archives of Neurology. 2009 ; Vol. 66, No. 8. pp. 1016-1020.
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AU - Martin, Maria Del Pilar

AU - Cravens, Petra D.

AU - Winger, Ryan

AU - Kieseier, Bernd C.

AU - Cepok, Sabine

AU - Eagar, Todd N.

AU - Zamvil, Scott S.

AU - Weber, Martin S.

AU - Frohman, Elliot

AU - Kleinschmidt-DeMasters, Betty K.

AU - Montine, Thomas J.

AU - Hemmer, Bernhard

AU - Marra, Christina M.

AU - Stuve, Olaf

PY - 2009/8

Y1 - 2009/8

N2 - 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. Locationmatched 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:Wewere 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.

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