Abstract
Autoimmunity is the break of tolerance to self-antigens that leads to
organ-specific or systemic diseases characterized by the presence of
pathogenic autoreactive antibodies (AAb) produced by plasmablast and/or
plasma cells. AAb are prevalent in the general population and not
systematically associated with clinical symptoms. In contrast, in some
individuals, these AAb are pathogenic and drive the development of signs
and symptoms of antibody-mediated autoimmune diseases (AbAID). AAb
production, isotype profiles, and glycosylations are promoted by
pro-inflammatory triggers linked to genetic, environmental, and hormonal
parameters. Recent evidence supports a role for pathogenic AAb of the
IgE isotype in a number of AbAID. Autoreactive IgE can drive the
activation of mast cells, basophils and other types of FcεRI-bearing
cells and may play a role in promoting autoantibody production and other
pro-inflammatory pathways. In this review, we discuss the current
knowledge on the pathogenicity of autoreactive IgE in AbAID and their
status as therapeutic targets. We also highlight unresolved issues
including the need for assays that reproducibly quantify IgE AAbs, to
validate their diagnostic and prognostic value, and to further study
their pathophysiological contributions to AbAID.