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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Molecular Innate Immunity

This article is part of the Research TopicHarnessing Omic Sciences to Unravel Mechanisms and Therapeutic Targets in Allergic DiseasesView all 4 articles

Differential DNA methylation in infants with IgE- and non-IgE-mediated cow’s milk allergy and its association with acquired tolerance

Provisionally accepted
Rebeca  López-GómezRebeca López-Gómez1Marta  Gil-MartínezMarta Gil-Martínez2Ana  Ladrón-GuevaraAna Ladrón-Guevara1Jose  Manuel Rodrigo-MuñozJose Manuel Rodrigo-Muñoz2Clara  Lorente-SorollaClara Lorente-Sorolla1Daniel  Rodríguez-GonzálezDaniel Rodríguez-González2,3Zahara  García De CastroZahara García De Castro2Gema  Guillén-SánchezGema Guillén-Sánchez2Antonio  SerranoAntonio Serrano2Raquel  Mirasierra-PérezRaquel Mirasierra-Pérez1José  Antonio CañasJosé Antonio Cañas2,3*Genoveva  Del Río CamachoGenoveva Del Río Camacho1VICTORIA  DEL POZOVICTORIA DEL POZO2,3,4
  • 1University Hospital Fundación Jiménez Díaz, Madrid, Madrid, Spain
  • 2Department of Immunology, Health Research Institute Foundation Jimenez Diaz (IIS-FJD), Madrid, Asturias, Spain
  • 3CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Asturias, Spain
  • 4Autonomous University of Madrid, Madrid, Madrid, Spain

The final, formatted version of the article will be published soon.

Background: Cow's milk allergy (CMA) is one of the most common food allergies (FA) in childhood. This condition can be IgE-mediated, non-IgE-mediated, or a combination of both. Diagnosis involves clinical history in conjunction with sensitization tests. However, these tests have limited predictive value, making the oral food challenge (OFC) the gold standard for diagnosis. Recent research has focused on identifying biomarkers, including DNA methylation patterns, for FA diagnosis. The aim of this study is to investigate the differences in DNA methylation associated with distinct patterns of CMA, to identify new diagnostic biomarkers. Methods: Genome-wide DNA methylation profiling was performed on blood samples from infants with IgE-mediated CMA (CMAIE), non-IgE-mediated CMA (CMANIE), and non-allergic controls, at baseline and after 6 months of an exclusion diet in CMA groups. These results were then correlated with tolerance acquisition following the restrictive diet. Results: A total of 19 infants were enrolled (10 CMAIE, 6 CMANIE, and 3 controls). Significant differentially methylated regions (DMRs) annotated to both genes and promoters were identified in all groups, and a clear separation of the samples into their respective groups was observed. Furthermore, DMRs in promoters and genes were identified in tolerant CMAIE children after the exclusion diet, being associated to tolerance. Discussion: Differential DNA methylation in CMA children is a useful diagnostic biomarker, and it could also be valuable in predicting the resolution of such pathologies.

Keywords: food allergy, cow's milk allergy, epigenetic, Methylation, IgE-mediated, exclusiondiet, tolerance

Received: 06 Feb 2025; Accepted: 14 Nov 2025.

Copyright: © 2025 López-Gómez, Gil-Martínez, Ladrón-Guevara, Rodrigo-Muñoz, Lorente-Sorolla, Rodríguez-González, García De Castro, Guillén-Sánchez, Serrano, Mirasierra-Pérez, Cañas, Del Río Camacho and DEL POZO. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: José Antonio Cañas, toniosego@msn.com

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