The Effect of Natalizumab Therapy On Immune Surveillance of the Central Nervous System in Multiple Sclerosis Patients

Stüve, Olaf; Marra, Christina M.; Jerome, Keith R.; Cook, Linda; Cravens, Petra D.; Cepok, Sabine; Frohman, Elliot M.; Phillips, T. J.; Arendt, Gabriele; Hemmer, Bernhard; Monson, Nancy; Racke, Michael

doi:10.1016/j.clim.2006.04.421

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“…1 The result is a pronounced and sustained reduction of immune cell numbers in the CSF. 2 Less knowledge exists about natalizumab interfering with intrathecal humoral immune activities. Recently, disappearance of oligoclonal bands (OCB) during natalizumab therapy in 4 out of 6 patients was reported from von Glehn et al 3 This is very interesting and substantiates the importance of investigating intrathecal antibody production in response to natalizumab treatment because, in contrast to other CNS diseases including neuromyelitis optica 4 , CSF-restricted OCB have been reported to persist in MS. 5,6 Since CSF data from patients during natalizumab therapy is scarce, we collected CSF data from several specialized MS centers to obtain an appropriate sample size for determining significant changes in CNS-restricted humoral immune activity attributable to natalizumab therapy.…”

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confidence: 99%

Cerebrospinal fluid parameters of B cell-related activity in patients with active disease during natalizumab therapy

et al. 2012

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Recently, the disappearance of oligoclonal bands (OCBs) from the cerebrospinal fluid (CSF) of a few natalizumab-treated patients with multiple sclerosis (MS) has been reported. This is interesting since CSF-restricted OCB are believed to persist in MS. We pooled CSF data from 14 MS centers to obtain an adequate sample size for investigating the suspected changes in central nervous system (CNS)-restricted humoral immune activities in the context of natalizumab therapy. In a retrospective chart analysis, CSF parameters of blood-CSF barrier integrity and intrathecal IgG production from 73 natalizumab-treated MS patients requiring a diagnostic puncture for exclusion of progressive multifocal leukoencephalopathy were compared with CSF data obtained earlier in the course of disease before natalizumab therapy. At the time of repeat lumbar puncture, local IgG production (according to Reibergram) was significantly reduced (p < 0.0001) and OCB had disappeared in 16% of the patients. We therefore conclude that natalizumab therapy interferes with intrathecal antibody production at least in a significant number of patients. Recently, disappearance of oligoclonal bands (OCB) from the CSF of a few natalizumab-treated patients with MS has been reported. This is interesting since CSF-restricted OCB are considered to persists in MS.Since lumbar punctures during natalizumab therapy are infrequent we pooled CSF data from fourteen MS centers to obtain a suitable patient cohort for furhter investigations about the suspected impact of natalizumab on CNS-restricted humoral immune activities.In a retrospective chart analysis CSF parameters of blood-CSF barrier integrity and intrathecal IgG production from 73 natalizumab-treated MS patients requiring a diagnostic puncture for exclusion of progressive multifocal leukoencephalopathy were compared with CSF data obtained earlier in the course of disease before natalizumab therapy.

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