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Elevated serum and cerebrospinal fluid levels of soluble human herpesvirus type 6 cellular receptor, membrane cofactor protein, in patients with multiple sclerosis

Authors

  • Samantha S. Soldan MS,

    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
    2. Institute for Biomedical Sciences/Department of Genetics, George Washington University, Washington, DC
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  • Anna Fogdell-Hahn PhD,

    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • Meghan B. Brennan BA,

    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • Barbara B. Mittleman MD,

    1. National Institute of Arthritis, Musculoskeletal Skin Diseases, National Institutes of Health, Bethesda, MD
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  • Clara Ballerini PhD,

    1. Department of Neurology and Psychiatry, University of Florence, Florence, Italy
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  • Luca Massacesi MD,

    1. Department of Neurology and Psychiatry, University of Florence, Florence, Italy
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  • Tsukasa Seya MD, PhD,

    1. Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka Sijinbyo Center, Osaka, Japan
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  • Henry F. McFarland MD,

    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
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  • Steven Jacobson PhD

    Corresponding author
    1. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD
    • Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 9000 Rockville Pike, Building 10, Room 5B-16 Bethesda, MD 20892
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Abstract

Membrane cofactor protein (CD46) is a member of a family of glycoproteins that are regulators of complement and prevent activation of complement on autologous cells. Recently, CD46 has been identified as the cellular receptor for human herpesvirus Type 6 (HHV-6). Elevated levels of soluble CD46 have been described in several autoimmune disorders and may be implicated in the pathogenesis of these diseases. As several reports have supported an association of HHV-6 and multiple sclerosis, it was of interest to compare levels of soluble CD46 in the sera of MS patients to that of healthy controls, other neurological disease controls, and other inflammatory disease controls. Using an immunoaffinity column comprised of immobilized monoclonal antibodies to CD46, serum levels of soluble CD46 were found to be significantly elevated in multiple sclerosis patients compared with healthy and other neurological disease controls. Moreover, multiple sclerosis patients who tested positive for HHV-6 DNA in serum had significantly elevated levels of soluble CD46 in their serum compared with those who were negative for HHV-6 DNA. A significant increase in soluble CD46 was also found in the serum of other inflammatory disease controls tested compared with healthy controls. Additionally, a significant correlation was demonstrated between levels of soluble CD46 in the serum and cerebrospinal fluid of multiple sclerosis patients. Collectively, these data suggest that elevated levels of soluble CD46 may contribute to the pathogenesis of inflammatory diseases, including MS.

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