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Mult Scler. 2015 Jul;21(8):1036-44. doi: 10.1177/1352458514556296. Epub 2014 Nov 12.

Natalizumab exerts a suppressive effect on surrogates of B cell function in blood and CSF.

Author information

1
Department of Neurology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany clemens.warnke@med.uni-duesseldorf.de.
2
Department of Neurology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.
3
Department of Neurology, University of Ulm, Ulm, Germany.
4
National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA.
5
Department of Neurology, Ruhr University, Bochum, Germany.
6
Institute of Clinical Neuroimmunology, Ludwig Maximilian University and Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
7
Department of Neurology, Caritas Hospital, Bad Mergentheim, Germany.
8
Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hanover Medical School, Hanover, Germany.
9
Department of Neurology, Johannes Wesling Hospital Minden, Minden, Germany.
10
Department of Neurology, Merheim Hospital, Cologne, Germany.
11
Department of Neurology, Marienhospital Hamburg, Hamburg, Germany.
12
Department of Neurology, University Hospital Wuerzburg, Wuerzburg, Germany.
13
MS Center Amsterdam and Department of Radiology, Nuclear Medicine & PET Research, VU University Medical Center, Amsterdam, the Netherlands.
14
Department of Pharmacology and Clinical Neuroscience, Umea University Hospital, Umea, Sweden.
15
Department of Neurology, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
16
Institute for Clinical Chemistry and Laboratory Diagnostics, University Hospital Duesseldorf, Germany.
17
Institute for Virology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.

Abstract

BACKGROUND:

Natalizumab for multiple sclerosis (MS) increases the risk of progressive multifocal leukoencephalopathy (PML).

OBJECTIVE:

We aimed to assess the effect of natalizumab on cellular composition and functional B cell parameters including patients with natalizumab-associated PML (n=37).

METHODS:

Cellular composition by flow cytometry, levels of immunoglobulin (Ig)G/IgM by immunonephelometry, and oligoclonal bands by isoelectric focusing were studied in blood and cerebrospinal fluid.

RESULTS:

In MS patients treated with natalizumab without PML (n=59) the proportion of CD19+ B cells was higher in blood, but lower in cerebrospinal fluid compared with MS patients not treated with natalizumab (n=17). The CD4/CD8-ratio in cerebrospinal fluid was lower, and IgG and IgM levels as well as the IgG index dropped in longitudinal samples during natalizumab therapy. Oligoclonal bands persisted, but the total amount of the intrathecally produced IgG fraction, and the polyclonal intrathecal IgG reactivity to measles, rubella, and zoster declined. At the time of diagnosis of PML patients with natalizumab-associated PML had low total IgG levels in blood and cerebrospinal fluid.

CONCLUSIONS:

Natalizumab impacts B and T cell distribution and exerts an inhibitory effect on surrogates of B cell function in periphery and in cerebrospinal fluid, potentially contributing to the increased risk of developing PML.

KEYWORDS:

JC virus; Progressive multifocal leukoencephalopathy; Tysabri; disease-modifying therapies; immunosuppression; multiple sclerosis; natalizumab

PMID:
25392339
DOI:
10.1177/1352458514556296
[Indexed for MEDLINE]

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