Pathogenic mechanisms of IgE-mediated inflammation in self-destructive autoimmune responses.
Autoantibodies of the IgG subclass are pathogenic in a number of autoimmune disorders such as systemic lupus erythomatosus. The presence of circulating IgE autoantibodies in autoimmune patients has also been known for almost 40 years. Despite their role in allergies, IgE autoantibodies are not associated with a higher rate of atopy in these patients. However, recently they have been recognized as active drivers of autoimmunity through mechanisms involving the secretion of Type I interferons by plasmacytoid dendritic cells (pDC), the recruitment of basophils to lymph nodes, and the activation of adaptive immune responses through B and T cells. Here, we will review the formation, prevalence, affinity, and roles of the IgE autoantibodies that have been described in autoimmunity. We also present novel evidence supporting that triggering of IgE receptors in pDC induces LC3-associated phagocytosis, a cellular process also known as LAP that is associated with interferon responses. The activation of pDC with immune complexes formed by DNA-specific IgE antibodies also induce potent B-cell differentiation and plasma cell formation, which further define IgE's role in autoimmune humoral responses.
a Department of Respiratory , Inflammation & Autoimmunity, MedImmune LLC , Gaithersburg , MD , USA.
Rachel
R
Ettinger
a Department of Respiratory , Inflammation & Autoimmunity, MedImmune LLC , Gaithersburg , MD , USA.
Jodi L
JL
Karnell
a Department of Respiratory , Inflammation & Autoimmunity, MedImmune LLC , Gaithersburg , MD , USA.
Jill
J
Henault
a Department of Respiratory , Inflammation & Autoimmunity, MedImmune LLC , Gaithersburg , MD , USA.
Santosh K
SK
Panda
a Department of Respiratory , Inflammation & Autoimmunity, MedImmune LLC , Gaithersburg , MD , USA.
Jeffrey M
JM
Riggs
a Department of Respiratory , Inflammation & Autoimmunity, MedImmune LLC , Gaithersburg , MD , USA.
Roland
R
Kolbeck
a Department of Respiratory , Inflammation & Autoimmunity, MedImmune LLC , Gaithersburg , MD , USA.
Miguel A
MA
Sanjuan
D000818:Animals; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004198:Disease Susceptibility; D015322:Gene Rearrangement, B-Lymphocyte; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; D007073:Immunoglobulin E
Atopic dermatitis; B cells; IgE; autoimmunity; basophil; chronic spontaneous urticaria; class switch recombination; interferon; pemphigus bullous; plasmacytoid dendritic cells; systemic lupus erythematosus