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Food Allergy: Molecular Mechanisms, Clinical Challenges, and Future Directions

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 20 June 2026 | Viewed by 5392

Special Issue Editor

Special Issue Information

Dear Colleagues,

Food allergy is an increasingly prevalent immunological disorder that affects individuals of all ages and significantly impacts public health worldwide. It is characterized by adverse immune responses to specific dietary antigens and can manifest in a wide spectrum of clinical symptoms, ranging from mild cutaneous reactions to life-threatening anaphylaxis. Over the past decades, the incidence of food allergies has risen dramatically, particularly in industrialized countries, yet the underlying molecular and environmental drivers of this trend remain poorly understood.

The pathophysiology of food allergy involves complex interactions between genetic predisposition, environmental exposures, epithelial barrier dysfunction, and dysregulation of the immune system, particularly Th2-skewed responses and IgE-mediated mechanisms. Emerging evidence also highlights the potential role of the gut microbiome, epigenetic modifications, and non-IgE-mediated pathways in disease development and progression. Understanding these molecular mechanisms is critical for identifying novel biomarkers, improving diagnostics, and developing targeted therapeutic strategies.

Despite important advances in research, food allergy remains a major unmet clinical need. Current treatment options are limited, and management primarily relies on allergen avoidance and emergency interventions. There is an urgent need for innovative approaches to prevention, early diagnosis, and personalized treatment.

This Special Issue provides an excellent opportunity for scientists and clinicians working across immunology, molecular biology, allergy, and translational medicine to share their findings and contribute to advancing this critical area of research. I invite researchers and clinicians to contribute original research articles, reviews, and perspectives that deepen our understanding of the molecular and cellular bases of food allergy. Submissions addressing immunological pathways, genetic and epigenetic factors, novel diagnostic tools, therapeutic innovations, and translational research are especially welcome. By fostering interdisciplinary collaboration and disseminating high-quality research, we aim to accelerate scientific progress and improve outcomes for individuals affected by food allergies.

Dr. Sylwia Smolińska
Guest Editor

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Keywords

  • food allergy
  • allergen
  • environmental exposures
  • gut microbiome
  • non-IgE-mediated pathways

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Published Papers (4 papers)

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Research

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17 pages, 1873 KB  
Article
Extracellular Vesicles from Monocyte-Derived Dendritic Cells Modulate Lymphocyte and Eosinophil Responses in Cow’s Milk Allergy
by Antonio Serrano-Santiago, Daniel Rodríguez-González, Gema Guillén-Sánchez, Álvaro Arranz-Fragua, Rebeca López-Gómez, Ana Ladrón-Guevara, Rosa María Luz-Romero, Raquel Mirasierra-Pérez, Genoveva del Río Camacho, Victoria del Pozo and José Antonio Cañas
Int. J. Mol. Sci. 2026, 27(4), 1977; https://doi.org/10.3390/ijms27041977 - 19 Feb 2026
Cited by 1 | Viewed by 436
Abstract
Cow’s milk allergy (CMA) is characterized by an exaggerated immune response where dendritic cells (DCs) play a crucial role. Additionally, extracellular vesicles (EVs) can be released by immune cells, modulating this allergic response. Moreover, eosinophils also contribute to tissue damage and perpetuate inflammation [...] Read more.
Cow’s milk allergy (CMA) is characterized by an exaggerated immune response where dendritic cells (DCs) play a crucial role. Additionally, extracellular vesicles (EVs) can be released by immune cells, modulating this allergic response. Moreover, eosinophils also contribute to tissue damage and perpetuate inflammation in allergic reactions. Therefore, the aim of this work was to study the role of EVs from monocyte-derived dendritic cells (moDCs) on eosinophil and lymphocytes in CMA. Sixteen infants with IgE-mediated cow’s milk allergy (CMAIE) and three non-allergic controls were recruited. Peripheral blood monocytes were purified and differentiated to moDCs. EVs were obtained from the culture supernatant by ultracentrifugation and characterized by nanoparticle tracking analysis and Western blot. Interaction among EVs, eosinophils and peripheral blood mononuclear cells (PBMCs) were analyzed with confocal microscopy. Additionally, these cells were incubated with EVs to assess lymphocyte proliferation, as well as eosinophil migration and reactive oxygen species (ROS) production by flow cytometry. Moreover, multiplex analysis was performed to evaluate the cytokines released by PBMCs following stimulation with EVs. Proteins characteristic of EVs were identified (CD9, CD63, CD81 and Alix). Furthermore, the size of the nanovesicles was ~185 nm, which is consistent with previously published reports. Confocal microscopy revealed that EVs internalized and localized in the cytoplasm of eosinophils, while in PBMCs, EVs were located in the perinuclear region. A proliferation assay revealed an increase in the proliferation of Th1 and Th2 lymphocytes, with higher levels of IL-4. Moreover, EVs were able to significantly increase eosinophil ROS production and migration. However, these effects were not observed after stimulation with EVs from non-allergic controls. This exploratory study shows that EVs from the moDCs of children with CMAIE could induce chemotactic and stimulatory functions on eosinophils and lymphocytes, which could perpetuate inflammation and contribute to tissue damage in this type of allergy. Full article
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Review

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26 pages, 2090 KB  
Review
Wheat Allergy in the Era of Precision Medicine: From Novel Molecular Markers to New Therapeutic Perspectives
by Solomiya Pukalyak, Weronika Gromek, Aleksandra Tomczak, Ewa Markut-Miotła, Maja Woźniak, Mariusz Wysokiński, Sylwia Smolinska and Emilia Majsiak
Int. J. Mol. Sci. 2026, 27(4), 1717; https://doi.org/10.3390/ijms27041717 - 10 Feb 2026
Cited by 1 | Viewed by 962
Abstract
Wheat allergy (WA) poses a diagnostic challenge due to its diverse clinical phenotypes—ranging from classic food allergy and wheat-dependent exercise-induced anaphylaxis (WDEIA) to baker’s asthma. An additional diagnostic aspect is serological cross-reactivity with grass pollen. Undoubtedly, the transition from extract-based diagnostics to precise [...] Read more.
Wheat allergy (WA) poses a diagnostic challenge due to its diverse clinical phenotypes—ranging from classic food allergy and wheat-dependent exercise-induced anaphylaxis (WDEIA) to baker’s asthma. An additional diagnostic aspect is serological cross-reactivity with grass pollen. Undoubtedly, the transition from extract-based diagnostics to precise component-based diagnostics (CRDs) facilitates the management of wheat allergy. It has significantly improved the diagnostic accuracy for WDEIA ω-5-gliadin (Tri a 19), although considering new knowledge about wheat proteins, it seems necessary to include them in the diagnostic scheme, especially where Tri a 19 remains negative despite clinical symptoms. Therefore, in this review, we evaluate the clinical utility of new wheat molecules with a high risk of anaphylaxis. We pay particular attention to Tri a 37 (α-purothionin), a thermally stable allergen associated with a 4-fold increase in the risk of severe anaphylaxis, and Tri a 36 (LMW glutenin), which shows higher sensitivity than Tri a 19 in specific pediatric cohorts. In addition, we emphasize the role of Tri a 14 (nsLTP) in distinguishing true wheat sensitization from pollen-related cross-reactivity caused by profilins (Tri a 12) or carbohydrate determinants (CCDs). Beyond diagnostics, the review discusses dynamic changes in sensitization profiles in relation to the allergic march and the phenomenon of spontaneous remission in children. New management strategies are also discussed, including the potential of omalizumab (based on the data from the OUtMATCH study) in facilitating the reintroduction of allergens into the diet. Full article
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14 pages, 1717 KB  
Review
Linear Epitope-Mediated Immunological Cross-Reactivity in Livestock Product Allergens
by Pengmei An and Yanjun Cong
Int. J. Mol. Sci. 2026, 27(4), 1628; https://doi.org/10.3390/ijms27041628 - 7 Feb 2026
Viewed by 445
Abstract
Linear epitopes, comprising continuous amino acid sequences, are critically implicated in the immunological cross-reactivity of livestock products owing to their stability during food processing. This paper aims to comprehensively review linear epitope-mediated cross-allergic reactions in major livestock products, including milk, eggs, and meat. [...] Read more.
Linear epitopes, comprising continuous amino acid sequences, are critically implicated in the immunological cross-reactivity of livestock products owing to their stability during food processing. This paper aims to comprehensively review linear epitope-mediated cross-allergic reactions in major livestock products, including milk, eggs, and meat. Furthermore, this review systematically delineates the pathophysiological mechanisms underlying classical cross-allergic reactions, including α-Gal syndrome and avian egg syndrome, while addressing novel cross-reactive allergens, such as the thermostable poultry meat allergen Gal d 7 and the egg–milk cross-reactive protein α-vitellin, alongside their respective linear B-cell epitope profiles. Finally, this study summarizes the roles of these cross-reactive allergens in precise diagnosis and targeted therapy, providing a theoretical basis for future in-depth research on food cross-allergenic mechanisms. Full article
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28 pages, 546 KB  
Review
Basophil Activation Test (BAT) for Diagnosing LTP Food Allergy: Where Do We Stand Now? A Systematic Review
by Bernadetta Kosztulska, Magdalena Grześk-Kaczyńska, Magdalena Rydzyńska, Zbigniew Bartuzi and Natalia Ukleja-Sokołowska
Int. J. Mol. Sci. 2025, 26(21), 10401; https://doi.org/10.3390/ijms262110401 - 26 Oct 2025
Cited by 2 | Viewed by 2767
Abstract
LTP allergy and its accurate diagnosis remain a challenge in modern allergology. Patients sensitized to lipid transfer proteins (LTPs) present a wide range of symptoms, from mild manifestations—such as oral allergy syndrome, urticaria, and angioedema—to severe systemic reactions, including anaphylaxis. Oral food challenges [...] Read more.
LTP allergy and its accurate diagnosis remain a challenge in modern allergology. Patients sensitized to lipid transfer proteins (LTPs) present a wide range of symptoms, from mild manifestations—such as oral allergy syndrome, urticaria, and angioedema—to severe systemic reactions, including anaphylaxis. Oral food challenges (OFCs), the gold standard in food allergy diagnostics, are problematic in this group of patients due to the high risk of life-threatening reactions during the procedure. The basophil activation test (BAT), a functional assay based on flow cytometry, is a promising diagnostic tool that may benefit many food-allergic patients by reducing the need for OFCs. In 2023, BAT was incorporated into selected diagnostic pathways for food sensitization in the guidelines issued by the European Academy of Allergy and Clinical Immunology (EAACI). While many studies have investigated BAT in the context of peanut allergy, evidence regarding its application in LTP allergy remains limited. In this systematic review, we analyzed the currently available studies on the use of BAT in the diagnosis of LTP sensitization and evaluated its potential to supplement or even replace OFCs in specific clinical scenarios. Full article
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