title: Self-reactive IgE exacerbates interferon responses associated with autoimmunity.
abstract: Canonically, immunoglobulin E (IgE) mediates allergic immune responses by triggering mast cells and basophils to release histamine and type 2 helper cytokines. Here we found that in human systemic lupus erythematosus (SLE), IgE antibodies specific for double-stranded DNA (dsDNA) activated plasmacytoid dendritic cells (pDCs), a type of cell of the immune system linked to viral defense, which led to the secretion of substantial amounts of interferon-α (IFN-α). The concentration of dsDNA-specific IgE found in patient serum correlated with disease severity and greatly potentiated pDC function by triggering phagocytosis via the high-affinity FcɛRI receptor for IgE, followed by Toll-like receptor 9 (TLR9)-mediated sensing of DNA in phagosomes. Our findings expand the known pathogenic mechanisms of IgE-mediated inflammation beyond those found in allergy and demonstrate that IgE can trigger interferon responses capable of exacerbating self-destructive autoimmune responses.
authors.affiliation: Research Department, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Henault
authors.affiliation: Research Department, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Riggs
authors.affiliation: Research Department, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Jodi L
authors.initials: JL
authors.lastname: Karnell
authors.affiliation: Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois, USA.
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Liarski
authors.affiliation: Research Department, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Li
authors.affiliation: Antibody Discovery and Protein Engineering Department, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Lena
authors.initials: L
authors.lastname: Shirinian
authors.affiliation: Antibody Discovery and Protein Engineering Department, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Xu
authors.affiliation: Research Department, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Casey
authors.affiliation: Research Department, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Smith
authors.affiliation: Research Department, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Deepak B
authors.initials: DB
authors.lastname: Khatry
authors.affiliation: Research Department, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Liat
authors.initials: L
authors.lastname: Izhak
authors.affiliation: Antibody Discovery and Protein Engineering Department, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Clarke
authors.affiliation: Research Department, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Herbst
authors.affiliation: Research Department, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Ettinger
authors.affiliation: Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Petri
authors.affiliation: Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois, USA.
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Clark
authors.affiliation: Research Department, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Tomas
authors.initials: T
authors.lastname: Mustelin
authors.affiliation: Research Department, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Roland
authors.initials: R
authors.lastname: Kolbeck
authors.affiliation: Research Department, MedImmune, Gaithersburg, Maryland, USA.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanjuan
mesh_terms: D000974:Antibodies, Antinuclear / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007372:Interferons / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology / Q000378:metabolism; D008181:Lupus Nephritis / Q000276:immunology / Q000473:pathology; D008297:Male; D010587:Phagocytosis / Q000276:immunology; D010588:Phagosomes / Q000378:metabolism; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism
chemical_list: D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D016207:Cytokines; D007074:Immunoglobulin G; D051217:Toll-Like Receptor 9; D007073:Immunoglobulin E; D007372:Interferons