Immune surveillance in multiple sclerosis patients treated with natalizumab

Authors

  • Olaf Stüve MD,

    Corresponding author
    1. Neurology Section, VA North Texas Health Care System, Medical Service, Dallas, TX
    2. Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX
    3. Department of Neurology, the Heinrich Heine University, Düsseldorf, Germany
    • Department of Neurology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9036
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  • Christina M. Marra MD,

    1. Department of Neurology, University of Washington, Seattle, WA
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  • Keith R. Jerome MD, PhD,

    1. Department of Laboratory Medicine, University of Washington, Seattle, WA
    2. Fred Hutchinson Cancer Research Center, Seattle, WA
    3. Department of Neurology, Heinrich Heine University, Düsseldorf, Germany
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  • Linda Cook PhD,

    1. Department of Laboratory Medicine, University of Washington, Seattle, WA
    2. Fred Hutchinson Cancer Research Center, Seattle, WA
    3. Department of Neurology, Heinrich Heine University, Düsseldorf, Germany
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  • Petra D. Cravens PhD,

    1. Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX
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  • Sabine Cepok PhD,

    1. Department of Neurology, the Heinrich Heine University, Düsseldorf, Germany
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  • Elliot M. Frohman MD, PhD,

    1. Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX
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  • J. Theodore Phillips MD, PhD,

    1. Multiple Sclerosis Center at Texas Neurology, Dallas, TX
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  • Gabriele Arendt MD,

    1. Department of Neurology, the Heinrich Heine University, Düsseldorf, Germany
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  • Bernhard Hemmer MD,

    1. Department of Neurology, the Heinrich Heine University, Düsseldorf, Germany
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  • Nancy L. Monson PhD,

    1. Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX
    2. Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX
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  • Michael K. Racke MD

    1. Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX
    2. Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX
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Abstract

Objective

Our objective was to test whether natalizumab, an antibody against very late activating antigen (VLA)-4, interferes with central nervous system immune surveillance as assessed by leukocyte cell numbers and cellular phenotypes in cerebrospinal fluid (CSF) and peripheral blood.

Methods

Cell numbers and cellular phenotypes in CSF and peripheral blood were analyzed in multiple sclerosis (MS) patients treated with natalizumab, untreated MS patients, and patients with other neurological disease (OND). JC virus DNA in the CSF and peripheral blood was quantified by kinetic polymerase chain reaction.

Results

CSF leukocyte counts, CD4+ and CD8+ T cells, CD19+ B cells, and CD138+ plasma cells were significantly lower in natalizumab-treated MS patients compared with OND patients and untreated MS patients. JC virus DNA was not detected in CSF or peripheral blood from natalizumab-treated patients. Six months after cessation of natalizumab therapy, low lymphocyte counts in the CSF persisted. The patient with the highest total leukocyte and CD4+ and CD8+T-cell counts in the CSF experienced a clinical relapse.

Interpretation

These data suggest that natalizumab treatment results in a prolonged decrease of lymphocytes in the CSF and are consistent with the hypothesis that natalizumab impairs immune surveillance of the central nervous system. Ann Neurol 2006;59:743–747

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