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Evidence of kinetic proofreading through allergen specific IgE at the human mast cell IgE receptor
  • +5
  • Hans Jürgen Hoffmann,
  • Charlotte Hjort,
  • Jesper Just,
  • Lars I. Andersson,
  • Craig Wheelock,
  • Sven-Erik Dahlén,
  • Peter Adler Würtzen,
  • Lars Christensen
Hans Jürgen Hoffmann
Aarhus Universitet Faculty of Health

Corresponding Author:hjh@clin.au.dk

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Charlotte Hjort
Aarhus Universitet Faculty of Health
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Jesper Just
Aarhus Universitet Faculty of Health
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Lars I. Andersson
Karolinska Institutet
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Craig Wheelock
Karolinska Institutet
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Sven-Erik Dahlén
Karolinska Institutet
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Peter Adler Würtzen
Alk-Abello A/S
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Lars Christensen
Alk-Abello A/S
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Abstract

Background Activation of mast cells through IgE results in secretion and shedding of mast cell proteins and in vivo models suggest that these processes are governed by IgE antibody affinity. Methods We passively sensitized cultured primary human mast cells with recombinant human IgE clones with either high or low affinity for Der p 2, with a 200-fold affinity difference, and activated them with recombinant allergen. Activation was assessed by CD63 upregulation and PGD 2 secretion. Supernatants collected from mast cells activated for 0, 3, 6 and 24 hours were assessed for PGD 2 and inflammatory mediators on the OLINK platform at repeated time points. Results CD63 upregulation and PGD 2 synthesis scaled with affinity, as did secretion of cytokines like IL-8 and IL-13. Secretion of chemokines like CCL3 and CCL4 appeared to depend less on affinity, whereas shedding of surface markers CD40, SLAMF4 and CD5, and secretion of intracellular markers SIRT2 and CASP-8, were elevated by stimulation through low affinity IgE compared with high affinity IgE, illustrating differential responses dependent on the affinity of IgE. Conclusion Cytokine secretion and shedding of surface receptors of sensitized, cultured primary human mast cells is differentially regulated depending on the affinity of IgE for the Der p 2 allergen and may shape the chronic response to repeated allergic activation.
19 Jun 2023Submitted to Allergy
21 Jun 2023Submission Checks Completed
21 Jun 2023Assigned to Editor
21 Jun 2023Review(s) Completed, Editorial Evaluation Pending
24 Jun 2023Reviewer(s) Assigned
12 Jul 2023Editorial Decision: Revise Minor
19 Nov 20231st Revision Received
19 Nov 2023Submission Checks Completed
19 Nov 2023Assigned to Editor
19 Nov 2023Review(s) Completed, Editorial Evaluation Pending
19 Nov 2023Reviewer(s) Assigned