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Lookup NU author(s): Dr Louise MichaelisORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025 Hendrickx et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Immunoglobulin E (IgE)-mediated cow’s milk allergy (CMA) is an immune-mediated reaction to cow’s milk (CM). Non-IgE-mediated CMA resolves in most children in the first years of life, whereas IgE-mediated CMA outgrowth is often later or not at all. The exact mechanisms underlying resolution of IgE-mediated CMA are not fully understood. We aim to gain insight in the immunological mechanisms underlying resolution of IgE-mediated CMA by analyzing unique saliva samples of allergic infants using the Olink® Target 96 Inflammation panel. Twenty-four children who outgrew their CMA after 12 months were compared to 15 with persistent CMA. Persistent CMA was accompanied by an increase in interleukin-15 receptor subunit alpha in the first 6 months, followed by a decrease, hinting towards an initial increased T cell response. At the same time caspase-8 was increased and interleukin-7 was decreased in persistent CMA. For CMA resolution, we found elevated levels of delta and notch-like epidermal growth factor-related receptor. Furthermore, adenosine deaminase (ADA) increased significantly between 0 and 12 months in resolved CMA, but not in persistent CMA. KEGG pathway analysis suggests mainly the TNF signaling pathway to be important in the resolution of CM allergy. Our findings show that Olink® Target 96 Inflammation panel analysis of saliva samples can reveal potential immunological markers and mechanisms involved in CMA resolution.
Author(s): Hendrickx DM, Long M, Wopereis H, van der Molen RG, Belzer C, Chatchatee P, Nowak-Wegrzyn A, Lange L, Benjaponpitak S, Chong KW, Sangsupawanich P, van Ampting MTJ, Oude Nijhuis MM, Harthoorn LF, Langford JE, Knol J, Knipping K, Garssen J, Trendelenburg V, Pesek R, Davis CM, Muraro A, Erlewyn-Lajeunesse M, Fox AT, Michaelis LJ, Beyer K, Noimark L, Stiefel G, Schauer U, Hamelmann E, Peroni D, Boner A
Publication type: Article
Publication status: Published
Journal: PLoS ONE
Year: 2025
Volume: 20
Issue: 9
Online publication date: 10/09/2025
Acceptance date: 16/08/2025
Date deposited: 30/09/2025
ISSN (electronic): 1932-6203
Publisher: Public Library of Science
URL: https://doi.org/10.1371/journal.pone.0331462
DOI: 10.1371/journal.pone.0331462
Data Access Statement: The Olink Target 96 Inflammation panel data and R code have been deposited in Gitlab (https://git.wur.nl/afsg-microbiology/publication-supplementary-materials/2024-hendrickx-et-al-earlyfit-presto-immune-study). The clinical study data supporting the findings of this study are available on request from Danone Research & Innovation (Uppsalalaan 12, 3584 CT Utrecht, The Netherlands, https://www.danoneresearch.com/ ); understanding that there could be reasonable caveats for such requests. Researchers that meet the criteria for access to confidential clinical study data must be compliant with the Danone Research & Innovation Clinical Trial Dataset Sharing policy. Danone conducts clinical studies according to the ICH-GCP guidelines, the Declaration of Helsinki, and the WHO code. In addition, the quality management system of Danone for clinical research has been ISO 9001 certified since 2007 and has been recertified every three years. [See article for the full Data Availability Statement.]
PubMed id: 40929127
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