Endotyping of IgE-Mediated Polyethylene Glycol and/or Polysorbate 80 Allergy.

Autor:	Ieven T; KU Leuven Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium; Department of General Internal Medicine, Division of Allergy and Clinical Immunology, University Hospitals Leuven, Leuven, Belgium., Coorevits L; KU Leuven Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium; Department of General Internal Medicine, Division of Allergy and Clinical Immunology, University Hospitals Leuven, Leuven, Belgium., Vandebotermet M; Department of General Internal Medicine, Division of Allergy and Clinical Immunology, University Hospitals Leuven, Leuven, Belgium; Department of Pulmonology, AZ Groeninge Hospital, Kortrijk, Belgium., Tuyls S; Department of General Internal Medicine, Division of Allergy and Clinical Immunology, University Hospitals Leuven, Leuven, Belgium; Department of Pulmonology, GZA St-Augustinus Hospital, Wilrijk, Belgium., Vanneste H; Department of General Internal Medicine, Division of Allergy and Clinical Immunology, University Hospitals Leuven, Leuven, Belgium; Department of Pulmonology, AZ Vesalius, Tongeren, Belgium., Santy L; Department of General Internal Medicine, Division of Allergy and Clinical Immunology, University Hospitals Leuven, Leuven, Belgium; Department of Internal Medicine, Division of Pulmonology, St-Jozefskliniek, Izegem, Belgium., Wets D; Department of General Internal Medicine, Division of Allergy and Clinical Immunology, University Hospitals Leuven, Leuven, Belgium., Proost P; KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Molecular Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium., Frans G; Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium., Devolder D; Pharmacy Department, University Hospitals Leuven, Leuven, Belgium., Breynaert C; KU Leuven Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium; Department of General Internal Medicine, Division of Allergy and Clinical Immunology, University Hospitals Leuven, Leuven, Belgium., Bullens DMA; KU Leuven Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium; Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium., Schrijvers R; KU Leuven Department of Microbiology, Immunology and Transplantation, Allergy and Clinical Immunology Research Group, KU Leuven, Leuven, Belgium; Department of General Internal Medicine, Division of Allergy and Clinical Immunology, University Hospitals Leuven, Leuven, Belgium. Electronic address: rik.schrijvers@uzleuven.be.
Jazyk:	angličtina
Zdroj:	The journal of allergy and clinical immunology. In practice [J Allergy Clin Immunol Pract] 2023 Oct; Vol. 11 (10), pp. 3146-3160. Date of Electronic Publication: 2023 Jun 26.
DOI:	10.1016/j.jaip.2023.06.031
Abstrakt:	Background: Polyethylene glycol (PEG) and polysorbate 80 (PS80) allergy preclude from SARS-CoV-2 vaccination. The mechanism(s) governing cross-reactivity and PEG molecular weight dependence remain unclear. Objectives: To evaluate PEGylated lipid nanoparticle (LNP) vaccine (BNT162b2) tolerance and explore the mechanism of reactivity in PEG and/or PS80 allergic patients. Methods: PEG/PS80 dual- (n = 3), PEG mono- (n = 7), and PS80 mono-allergic patients (n = 2) were included. Tolerability of graded vaccine challenges was assessed. Basophil activation testing on whole blood (wb-BAT) or passively sensitized donor basophils (allo-BAT) was performed using PEG, PS80, BNT162b2, and PEGylated lipids (ALC-0159). Serum PEG-specific IgE was measured in patients (n = 10) and controls (n = 15). Results: Graded BNT162b2 challenge in dual- and PEG mono-allergic patients (n = 3/group) was well tolerated and induced anti-spike IgG seroconversion. PS80 mono-allergic patients (n = 2/2) tolerated single-dose BNT162b2 vaccination. Wb-BAT reactivity to PEG-containing antigens was observed in dual- (n = 3/3) and PEG mono- (n = 2/3), but absent in PS80 mono-allergic patients (n = 0/2). BNT162b2 elicited the highest in vitro reactivity. BNT162b2 reactivity was IgE mediated, complement independent, and inhibited in allo-BAT by preincubation with short PEG motifs, or detergent-induced LNP degradation. PEG-specific IgE was only detectable in dual-allergic (n = 3/3) and PEG mono-allergic (n = 1/6) serum. Conclusion: PEG and PS80 cross-reactivity is determined by IgE recognizing short PEG motifs, whereas PS80 mono-allergy is PEG-independent. PS80 skin test positivity in PEG allergics was associated with a severe and persistent phenotype, higher serum PEG-specific IgE levels, and enhanced BAT reactivity. Spherical PEG exposure via LNP enhances BAT sensitivity through increased avidity. All PEG and/or PS80 excipient allergic patients can safely receive SARS-CoV-2 vaccines. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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