Multiple sclerosis

Authors

  • David A. Hafler,

    Corresponding author
    1. Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
    2. The Broad Institute, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
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  • Jacqueline M. Slavik,

    1. Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
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  • David E. Anderson,

    1. Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
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  • Kevin C. O'Connor,

    1. Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
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  • Philip De Jager,

    1. Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
    2. The Broad Institute, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
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  • Clare Baecher-Allan

    1. Laboratory of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
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* Dr David A. Hafler, MD
Center for Neurologic Diseases
Harvard Medical School
77 Avenue Louis Pasteur
Boston, MA 02115
USA
Tel: 617 525 5330
Fax: 617 525 5333
E-mail: dhafler@rics.bwh.harvard.edu

Abstract

Summary:  Multiple sclerosis (MS) is a complex genetic disease associated with inflammation in the central nervous system (CNS) white matter and is thought to be mediated by autoimmune processes. Clonal expansion of B cells, their antibody products, and T cells, hallmarks of inflammation in the CNS, are found in MS. The association of the disease with major histocompatibility complex genes, the inflammatory white matter infiltrates, similarities with animal models, and the observation that MS can be treated with immunomodulatory and immunosuppressive therapies support the hypothesis that autoimmunity plays a major role in the disease pathology.

This review discusses the immunopathology of MS with particular focus given to regulatory T cells and the role of B cells and antibodies, immunomodulatory therapeutics, and finally new directions in MS research, particularly new methods to define the molecular pathology of human disease with high-throughput examination of germline DNA haplotypes, RNA expression, and protein structures that will allow the generation of a new series of hypotheses that can be tested to develop better understandings and therapies for this disease.

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