Depletion of B lymphocytes from cerebral perivascular spaces by rituximab

Research output: Contribution to journalArticle

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

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 1 2009

PMID: 19667224

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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 M.; Kleinschmidt-DeMasters, Betty K.; Montine, Thomas J.; Hemmer, Bernhard; Marra, Christina M.; Stüve, Olaf.

In: Archives of neurology, Vol. 66, No. 8, 01.08.2009, p. 1016-1020.

Research output: Contribution to journalArticle

Harvard

Martin, MDP, Cravens, PD, Winger, R, Kieseier, BC, Cepok, S, Eagar, TN, Zamvil, SS, Weber, MS, Frohman, EM, Kleinschmidt-DeMasters, BK, Montine, TJ, Hemmer, B, Marra, CM & Stüve, 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

APA

Martin, M. D. P., Cravens, P. D., Winger, R., Kieseier, B. C., Cepok, S., Eagar, T. N., ... Stüve, 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

Vancouver

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 1;66(8):1016-1020. https://doi.org/10.1001/archneurol.2009.157

Author

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 M. ; Kleinschmidt-DeMasters, Betty K. ; Montine, Thomas J. ; Hemmer, Bernhard ; Marra, Christina M. ; Stüve, Olaf. / Depletion of B lymphocytes from cerebral perivascular spaces by rituximab. In: Archives of neurology. 2009 ; Vol. 66, No. 8. pp. 1016-1020.

BibTeX

@article{fc50be6a6fc9463eb3da65e09650e131,
title = "Depletion of B lymphocytes from cerebral perivascular spaces by rituximab",
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.",
author = "Martin, {Maria Del Pilar} and Cravens, {Petra D.} and Ryan Winger and Kieseier, {Bernd C.} and Sabine Cepok and Eagar, {Todd N.} and Zamvil, {Scott S.} and Weber, {Martin S.} and Frohman, {Elliot M.} and Kleinschmidt-DeMasters, {Betty K.} and Montine, {Thomas J.} and Bernhard Hemmer and Marra, {Christina M.} and Olaf St{\"u}ve",
year = "2009",
month = "8",
day = "1",
doi = "10.1001/archneurol.2009.157",
language = "English (US)",
volume = "66",
pages = "1016--1020",
journal = "Archives of Neurology",
issn = "0003-9942",
publisher = "American Medical Association",
number = "8",

}

RIS

TY - JOUR

T1 - Depletion of B lymphocytes from cerebral perivascular spaces by rituximab

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 M.

AU - Kleinschmidt-DeMasters, Betty K.

AU - Montine, Thomas J.

AU - Hemmer, Bernhard

AU - Marra, Christina M.

AU - Stüve, Olaf

PY - 2009/8/1

Y1 - 2009/8/1

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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=68549083770&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68549083770&partnerID=8YFLogxK

U2 - 10.1001/archneurol.2009.157

DO - 10.1001/archneurol.2009.157

M3 - Article

VL - 66

SP - 1016

EP - 1020

JO - Archives of Neurology

T2 - Archives of Neurology

JF - Archives of Neurology

SN - 0003-9942

IS - 8

ER -

ID: 16797313