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A model for lupus brain disease

Authors

  • Betty Diamond,

    1. Center for Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA.
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  • Bruce T. Volpe

    1. Laboratory of Functional Neuroanatomy, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA.
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Betty Diamond
Center for Autoimmune and Musculoskeletal Diseases
The Feinstein Institute for Medical Research
350 Community
Dr. Manhasset, NY 11030, USA
Tel.: +1 516 562 3830
Fax: +1 516 562 2921
e-mail: bdiamond@nshs.edu

Abstract

Summary:  Systemic lupus erythematosus is an autoimmune disease characterized by antibodies that bind target autoantigens in multiple organs in the body. In peripheral organs, immune complexes engage the complement cascade, recruiting blood-borne inflammatory cells and initiating tissue inflammation. Immune complex-mediated activation of Fc receptors on infiltrating blood-borne cells and tissue resident cells amplifies an inflammatory cascade with resulting damage to tissue function, ultimately leading to tissue destruction. This pathophysiology appears to explain tissue injury throughout the body, except in the central nervous system. This review addresses a paradigm we have developed for autoantibody-mediated brain damage. This paradigm suggests that antibody-mediated brain disease does not depend on immune complex formation but rather on antibody-mediated alterations in neuronal activation and survival. Moreover, antibodies only access brain tissue when blood-brain barrier integrity is impaired, leading to a lack of concurrence of brain disease and tissue injury in other organs. We discuss the implications of this model for lupus and for identifying other antibodies that may contribute to brain disease.

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