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A model for lupus brain disease
Author(s) -
Diamond Betty,
Volpe Bruce T.
Publication year - 2012
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.2012.01137.x
Subject(s) - immune system , antibody , immunology , autoantibody , inflammation , systemic lupus erythematosus , biology , complement system , autoimmune disease , blood–brain barrier , disease , central nervous system , pathology , medicine , neuroscience
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.