Archives of neurology · 2009
Depletion of B lymphocytes from cerebral perivascular spaces by rituximab.
Клинический случайСтатьяПоддержка исследования: вне правительства СШАПоддержка правительства СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.
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.
Предметные рубрики MeSH
AgedAntibodies, MonoclonalAntibodies, Monoclonal, Murine-DerivedAntineoplastic AgentsB-LymphocytesBasal GangliaBrainCerebral VentriclesDominance, CerebralFemaleGastrointestinal NeoplasmsHumansLeukoencephalopathy, Progressive MultifocalLymphocyte CountLymphocyte DepletionLymphoma, Mantle-CellMagnetic Resonance ImagingMultiple Sclerosis, Relapsing-RemittingMyelin SheathNeurologic ExaminationRituximabSalvage Therapy