Rapid IgE desensitization is antigen specific and impairs early and late mast cell responses targeting FcεRI internalization

Authors

  • Maria del Carmen Sancho-Serra,

    1. Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
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  • Maria Simarro,

    1. Unidad de Investigacion, Hospital Clinico Universitario de Valladolid, Valladolid, Spain
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  • Mariana Castells

    Corresponding author
    1. Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
    • Brigham and Women's Hospital- Smith Building, Room 626D 1 Jimmy Fund Way Boston, MA 02115, USA Fax: +1-617-525-1310
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Abstract

Rapid IgE desensitization provides temporary tolerization for patients who have presented severe hypersensitivity reactions to food and drugs, protecting them from anaphylaxis, but the underlying mechanisms are still incompletely understood. Thus, here we develop an effective and reproducible in vitro model of rapid IgE desensitization for mouse BM-derived mast cells (BMMCs) under physiologic calcium conditions, and we characterize its antigen specificity and primary events. BMMCs were challenged with DNP-human serum albumin conjugated (DNP-HSA) and/or OVA antigens, delivered either as a single dose (activation) or as increasing sequential doses (desensitization). Compared to activated cells, desensitized BMMCs had impaired degranulation, calcium flux, secretion of arachidonic acid products, early and late TNF-α production, IL-6 production, and phosphorylation of STAT6 and p38 mitogen-activated protein kinase (p38 MAPK). OVA-desensitized cells responded to DNP and DNP-desensitized cells responded to OVA, proving specificity. Internalization of specific antigen, IgE and high-affinity receptor for IgE (FcεRI) were impaired in desensitized BMMCs. Our results demonstrate that rapid IgE desensitization is antigen specific and inhibits early and late mast cell activation responses and internalization of the antigen/IgE/FcεRI complexes.

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