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

Abstract

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.

Keywords

Natalizumab multiple sclerosis oligoclonal bands intrathecal IgG cerebrospinal fluid

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References

Polman

O’Connor

Havrdova

. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354: 899–910.

Stüve

Marra

Jerome

. Immune surveillance in multiple sclerosis patients treated with natalizumab. Ann Neurol 2006; 59: 743–747.

von Glehn

Farias

de Oliveira

. Disappearance of cerebrospinal fluid oligoclonal bands after natalizumab treatment of multiple sclerosis patients. Mult Scler 2012; 18: 1038–1041.

Jarius

Paul

Franciotta

. Cerebrospinal fluid findings in aquaporin-4 antibody positive neuromyelitis optica: Results from 211 lumbar punctures. J Neurol Sci 2011; 306: 82–90.

Petereit

Reske

. Expansion of antibody reactivity in the cerebrospinal fluid of multiple sclerosis patients — follow-up and clinical implications. Cerebrospinal Fluid Res 2005; 2: 3.

Reiber

. Cerebrospinal fluid — physiology, analysis and interpretation of protein patterns for diagnosis of neurological diseases. Mult Scler 1998; 4: 99–107.

Reiber

. Flow rate of cerebrospinal fluid (CSF) — a concept common to normal blood-CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci 1994; 122: 189–203.

Kowarik

Pellkofer

Cepok

. Differential effects of fingolimod (FTY720) on immune cells in the CSF and blood of patients with MS. Neurology 2011; 76: 1214–1221.

Piccio

Naismith

Trinkaus

. Changes in B- and T-lymphocyte and chemokine levels with rituximab treatment in multiple sclerosis. Arch Neurol 2010; 67: 707–714.

10.

von Budingen

Bar-Or

Zamvil

. B cells in multiple sclerosis: Connecting the dots. Curr Opin Immunol 2011; 23: 713–720.