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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.
Afiliación
  • Martin Mdel P; Department of Neurology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
Arch Neurol ; 66(8): 1016-20, 2009 Aug.
Article en En | MEDLINE | ID: mdl-19667224
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Linfocitos B / Leucoencefalopatía Multifocal Progresiva / Depleción Linfocítica / Linfoma de Células del Manto / Esclerosis Múltiple Recurrente-Remitente / Neoplasias Gastrointestinales / Anticuerpos Monoclonales / Vaina de Mielina / Antineoplásicos Tipo de estudio: Clinical_trials Límite: Aged / Female / Humans Idioma: En Revista: Arch Neurol Año: 2009 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Linfocitos B / Leucoencefalopatía Multifocal Progresiva / Depleción Linfocítica / Linfoma de Células del Manto / Esclerosis Múltiple Recurrente-Remitente / Neoplasias Gastrointestinales / Anticuerpos Monoclonales / Vaina de Mielina / Antineoplásicos Tipo de estudio: Clinical_trials Límite: Aged / Female / Humans Idioma: En Revista: Arch Neurol Año: 2009 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos