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Food allergies are defined as adverse immune responses to food proteins that result in typical clinical symptoms involving the dermatologic, respiratory, gastrointestinal, cardiovascular, and/or neurologic systems. IgE-mediated food-allergic disease differs from non-IgE-mediated disease because the pathophysiology results from activation of the imm...
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Basophil activation test (BAT) or the mast cell activation test (MAT) are two in vitro tests that are currently being studied in food allergy as diagnostic tools as an alternative to oral food challenges (OFCs). We conducted a meta‐analysis on BAT and MAT, assessing their specificity and sensitivity in diagnosing peanut allergy. Six databases were...
Citations
... Food allergy causes clinical symptoms systemically and/or locally in cutaneous, respiratory, ocular and gastrointestinal tissues. [1][2][3] Allergic enteritis (AE) is a clinical manifestation of gastrointestinal food allergy. 4 AE mimics in mice some traits observed in patients with food allergy-associated intestinal inflammation characterized by thicker basal layer, crypt elongation, villous atrophy and granulocyte infiltration. ...
Background
The pathological mechanism of the gastrointestinal forms of food allergies is less understood in comparison to other clinical phenotypes, such as asthma and anaphylaxis Importantly, high‐IgE levels are a poor prognostic factor in gastrointestinal allergies.
Methods
This study investigated how high‐IgE levels influence the development of intestinal inflammation and the metabolome in allergic enteritis (AE), using IgE knock‐in (IgEki) mice expressing high levels of IgE. In addition, correlation of the altered metabolome with gut microbiome was analysed.
Results
Ovalbumin‐sensitized and egg‐white diet‐fed (OVA/EW) BALB/c WT mice developed moderate AE, whereas OVA/EW IgEki mice induced more aggravated intestinal inflammation with enhanced eosinophil accumulation. Untargeted metabolomics detected the increased levels of N‐tau‐methylhistamine and 2,3‐butanediol, and reduced levels of butyric acid in faeces and/or sera of OVA/EW IgEki mice, which was accompanied with reduced Clostridium and increased Lactobacillus at the genus level. Non‐sensitized and egg‐white diet‐fed (NC/EW) WT mice did not exhibit any signs of AE, whereas NC/EW IgEki mice developed marginal degrees of AE. Compared to NC/EW WT mice, enhanced levels of lysophospholipids, sphinganine and sphingosine were detected in serum and faecal samples of NC/EW IgEki mice. In addition, several associations of altered metabolome with gut microbiome—for example Akkermansia with lysophosphatidylserine—were detected.
Conclusions
Our results suggest that high‐IgE levels alter intestinal and systemic levels of endogenous and microbiota‐associated metabolites in experimental AE. This study contributes to deepening the knowledge of molecular mechanisms for the development of AE and provides clues to advance diagnostic and therapeutic strategies of allergic diseases.
... The most frequent allergic reactions, known as IgE-mediate reactions, are brought on by the binding of allergen-specific IgE antibodies to basophils and mast cells. This causes the release of histamine and other inflammatory mediators, which lead to the manifestation of allergy symptoms [6,7]. Current medications and treatments used to manage persistent allergies often show limited effectiveness [8,9]. ...
Background
Allergic disorders, prevalent global health concerns, afflict a substantial portion of the world’s population. These maladies result from an exaggerated immune system response to ordinarily innocuous substances, such as pollen, dust mites, and specific dietary components. Clinical manifestations of this heightened immune response include itching, swelling, and respiratory impairment, often accompanied by releasing mediators like histamine. The pathophysiological mechanisms of allergy disorders are intricate, arising from a complex interplay between genetic and environmental factors. While clinical presentations may vary, all allergy conditions share a common foundation in the dysregulated immune response to allergens.
Result
The current aim of this study was to identify innovative anti-allergic agents capable of inhibiting histamine and effectively mitigating allergic reactions by utilizing the computer-aided drug design approach by discovery studio (DS) 2022 v 23.1.1 package. The overarching aim was identifying potential drug candidates targeting the active site within the histamine H1 receptor complex; therefore, a collection of 4000 small druggable compounds was curated from ZINC, PubChem, and DRUG BANK databases sources. Four compounds appeared as promising candidates after assessing docking scores and binding energies. Notably, Compound ID 34154, recognized as tymazoline, showed the highest affinity for the H1 receptor of 3RZE, suggesting it may be the most promising choice for more research. Further chemoinformatic and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analyses were conducted to assess the drug-like qualities of this chosen molecule. In addition, bioisosteric substitution techniques were employed to enhance tymazoline’s ADMET characteristics.
Conclusion
Tymazoline shows strong binding affinity with 3RZE and verified all the drug-likeness criteria to inhibit the allergic disorders. Furthermore, molecular dynamics (MD) studies corroborated tymazoline’s potential as an anti-allergic agent, demonstrating contact between the ligand and the receptor that is well defined and stable.
... T-regs encourage the maintenance of tolerance through the expression of CTLA-4, which inhibits Th2 T cells, and the release of the cytokines TGF-β and IL-10. TGF-β and IL-10 suppress mast cells, eosinophils, and basophils (the effector cells that promote allergic symptoms), promote the keeping of IgA in the intestinal lumen and the production of IgG4, and reduce the production of IgE by B cells [58]. The impairment of oral tolerance mechanisms can trigger the development of FA [59]. ...
... Sensitization is defined as the condition in which food-specific IgE is detectable in the serum, becoming a possible trigger factor for clinical manifestations of FA. This phase occurs when a food allergen crosses a compromised epithelial barrier and is captured by dendritic cells in a context of inflammatory cytokines such as thymic stromal lymphopoietin (TSLP), IL-25, and IL-33, thereby inducing a Th2-type response [58,[60][61][62]. Differentiated Th2 cells can migrate from draining lymph nodes into the intestinal lamina propria and secrete pro-inflammatory cytokines, such as IL-5 and IL-13, to further promote the differentiation of effector cells such as eosinophils and basophils [58,63,64]. ...
... This phase occurs when a food allergen crosses a compromised epithelial barrier and is captured by dendritic cells in a context of inflammatory cytokines such as thymic stromal lymphopoietin (TSLP), IL-25, and IL-33, thereby inducing a Th2-type response [58,[60][61][62]. Differentiated Th2 cells can migrate from draining lymph nodes into the intestinal lamina propria and secrete pro-inflammatory cytokines, such as IL-5 and IL-13, to further promote the differentiation of effector cells such as eosinophils and basophils [58,63,64]. In addition, innate lymphoid cells type 2 (ICL2) also play an important role in the onset of FA through the secretion of cytokines such as IL-4 and IL-13 [65]. ...
Food allergy (FA) has shown an increasing prevalence in the last decades, becoming a major public health problem. However, data on the prevalence of FA across the world are heterogeneous because they are influenced by several factors. Among IgE-mediated FA, an important role is played by FA related to plant-derived food which can result from the sensitization to a single protein (specific FA) or to homologous proteins present in different foods (cross-reactive FA) including non-specific lipid transfer proteins (nsLTPs), profilins, and pathogenesis-related class 10 (PR-10). In addition, the clinical presentation of FA is widely heterogeneous ranging from mild symptoms to severe reactions up to anaphylaxis, most frequently associated with nsLTP-related FA (LTP syndrome). Considering the potential life-threatening nature of nsLTP-related FA, the patient’s geographical setting should always be taken into account; thereby, it is highly recommended to build a personalized approach for managing FA across the world in the precision medicine era. For this reason, in this review, we aim to provide an overview of the prevalence of nsLTP-mediated allergies in the Mediterranean area and to point out the potential reasons for the different geographical significance of LTP-driven allergies with a particular focus on the allergenic properties of food allergens and their cross reactivity.
... In contrast to non-IgE mediational allergy, which has a delayed onset, IgE mediational allergy triggers the release of histamine and other mediators, leading to a rapid onset of symptoms [68]. Symptoms of IgE-mediated CMA symptoms include eczema and urticaria. ...
Bovine milk is an essential supplement due to its rich energy- and nutrient-rich qualities. Caseins constitute the vast majority of the proteins in milk. Among these, β-casein comprises around 37% of all caseins, and it is an important type of casein with several different variants. The A1 and A2 variants of β-casein are the most researched genotypes due to the changes in their composition. It is accepted that the A2 variant is ancestral, while a point mutation in the 67th amino acid created the A1 variant. The digestion derived of both A1 and A2 milk is BCM-7. Digestion of A2 milk in the human intestine also forms BCM-9 peptide molecule. The opioid-like characteristics of BCM-7 are highlighted for their potential triggering effect on several diseases. Most research has been focused on gastrointestinal-related diseases; however other metabolic and nervous system-based diseases are also potentially triggered. By manipulating the mechanisms of these diseases, BCM-7 can induce certain situations, such as conformational changes, reduction in protein activity, and the creation of undesired activity in the biological system. Furthermore, the genotype of casein can also play a role in bone health, such as altering fracture rates, and calcium contents can change the characteristics of dietary products. The context between opioid molecules and BCM-7 points to a potential triggering mechanism for the central nervous system and other metabolic diseases discussed.
... WAO systemic allergic reaction grading system[3]. ...
Food allergy (FA) has become a common global public health issue, with a growing prevalence in the modern world and a significant impact on the lives of patients, their families, and caregivers. It affects every area of life and is associated with elevated costs. Food allergy is an adverse immune reaction that occurs in response to a given food. The symptoms vary from mild to severe and can lead to anaphylaxis. This is why it is important to focus on the factors influencing the occurrence of food allergies, specific diagnostic methods, effective therapies, and especially prevention. Recently, many guidelines have emphasized the impact of introducing specific foods into a child’s diet at an early age in order to prevent food allergies. Childhood allergies vary with age. In infants, the most common allergy is to cow’s milk. Later in life, peanut allergy is more frequently diagnosed. Numerous common childhood allergies can be outgrown by adulthood. Adults can also develop new IgE-mediated FA. The gold standard for diagnosis is the oral provocation test. Skin prick tests, specific IgE measurements, and component-resolved diagnostic techniques are helpful in the diagnosis. Multiple different approaches are being tried as possible treatments, such as immunotherapy or monoclonal antibodies. This article focuses on the prevention and quality of life of allergic patients. This article aims to systematize the latest knowledge and highlight the differences between food allergies in pediatric and adult populations.
... In addition to environmental pollution, immunologic interactions with allergenic proteins, such as food and potentially insect bites, can trigger IgE-mediated allergic reactions. These interactions are potential contributors to the increasing incidence of this allergic airway disease [3,4]. ...
Background
Allergic rhinitis is a chronic respiratory disorder that significantly impacts patients’ quality of life (QoL) and work performance. Pharmacists are recognized as suitable professionals to provide patient education and pharmaceutical care for managing allergic rhinitis patients. However, local clinical practice guidelines, particularly regarding pharmaceutical care in public healthcare institutions, are lacking. This study protocol outlines a randomized controlled trial (RCT) designed to evaluate the effectiveness of a pharmacist-led educational model (AR-PRISE Model) in managing allergic rhinitis in adult patients compared to standard pharmaceutical care. The AR-PRISE model delivers patient educational material and a pharmaceutical care algorithm.
Method
This is a 6-month, single-center, prospective, randomized, two-arm, and parallel-group controlled trial. The trial recruits patients attending the otorhinolaryngology clinics of a tertiary referral hospital. Participants are randomized into control or intervention groups in a 1:1 ratio using permuted block randomization. The total number of participants estimated is 154, with each group requiring 77 participants. The control group receives standard pharmaceutical care, while the intervention group receives pharmacist-led education according to the AR-PRISE model. Both groups are assessed for middle turbinate endoscopy findings, disease severity, knowledge level, symptom control, medication adherence, and QoL at baseline and the end-of-study follow-up (day 180 ± 7). Depending on feasibility, intermediate follow-ups are conducted on days 60 ± 7 and 120 ± 7, either virtually or face-to-face. During intermediate follow-ups, participants are assessed for symptom control, medication adherence, and QoL. The intention-to-treat analysis includes all participants assigned to each group. An independent T-test compares the mean difference in knowledge level between the two groups. A two-way repeated measures ANOVA analysis is employed to determine between-group differences for scores of symptom control, adherence rate, and QoL. A P-value < 0.05 is considered statistically significant.
Discussion
This study protocol will provide a framework for conducting a randomized controlled trial (RCT) to evaluate the effectiveness of pharmacist-led education intervention in managing allergic rhinitis within public healthcare settings. The parameters measured in this trial will quantify outcomes associated with improvements in symptoms and QoL. By systematically assessing these outcomes, we aim to contribute valuable insights into the role of pharmacist-led interventions in enhancing the management of allergic rhinitis in public healthcare settings.
Trial registration
ClinicalTrials.gov NCT06027736. Registered on 9 July 2023—retrospectively registered.
... life-threatening allergic reaction. 2,3 More than 160 foods may cause FA, with varying prevalence rates by specific food and population affected. 4 Peanut allergy (PA) is one of the most common IgE-mediated FA in childhood. ...
Peanut allergy affects about 1%–3% of the pediatric population in the world, with an important increase in the last decades. Nowadays, international guidelines recommend the early introduction of peanuts in the infant diet, with poor information about the quantity and the frequency of the intake. Allergen immunotherapy may represent the only therapeutic strategy able to modify the natural history of peanut allergy. In particular, oral immunotherapy showed the most promising results in terms of efficacy, but with significant rates of adverse reactions, mostly gastrointestinal. In 2020, the Food and Drug Administration and the European Medicines Agency approved Palforzia®, an oral drug for patients aged 4–17 years. Several studies are ongoing to improve the tolerability of oral immunotherapy and standardize the desensitization protocols. Sublingual immunotherapy permits to offer much lower doses than oral immunotherapy, but fewer adverse events are shown. Subcutaneous immunotherapy is associated with the greatest systemic adverse effects. Epicutaneous immunotherapy, for which Viaskin® patch was approved, has the highest safety profile. Innovative studies are evaluating the use of biological drugs, such as omalizumab or dupilumab, and probiotics, such as Lactobacillus rhamnosus, in monotherapy or associated with oral immunotherapy. Therapy for peanut allergy is constantly evolving, and new perspectives are ongoing to develop. image
... These allergic mediators, such as histamine, tryptase, and serotonin, trigger FA attacks [5]. In general, the immune responses are tightly regulated by the immune regulatory system [6]. ...
The pathogenesis of food allergy (FA) is still not fully understood. Telomerases are involved in the regulation of immune responses. The aim of this study is to understand the contribution of telomerase reverse transcriptase (TERT) to the pathogenesis of FA. A murine FA model was established with ovalbumin as the specific antigen. This murine model was used to test the role of TERT in the regulation of dendritic cell (DC) immune tolerogenic functions. We observed that the Tert promoter was at demethylation status and the Tert expression was elevated in DCs of FA mice. The FA response was positively correlated with the Tert expression in DCs. Induction of Il10 expression in DCs was hindered by TERT. TERT hindered the immune tolerogenic functions of DCs. The immune tolerogenic functions of DC were restored by CpG by boosting the Tert promoter methylation. Administration of CpG promoted the therapeutic effects of allergen specific immunotherapy in FA mice. In conclusion, low levels of Il10 expression and high levels of Tert expression were observed in intestinal DCs of FA mice. CpG exposure restored the expression of Il10 and increased the therapeutic benefits of allergen-specific immunotherapy.
... IgE-mediated food allergy is a global health problem that affects millions of persons and affects every aspect of life for the patients. 46 A promising approach to treat food allergies is the use of oral immunotherapy (OIT). OIT consist in a gradual exposure to increasing amounts of allergen can lead to many subjects tolerating doses of food sufficient to prevent reaction on accidental exposure. ...
Immunotherapy, also known as biologic therapy or biotherapy, is a medical treatment that utilizes the immune system to combat diseases, including cancer. Over the past few decades, immunotherapy has emerged as an integral part of cancer treatment, with various approaches being explored. This article provides an overview of immunotherapy, its mechanisms of action, and the different types of immunomodulators involved. Activation immunotherapies aim to enhance the immune response, such as cancer vaccines and cellular therapies, while suppression immunotherapies work to reduce or suppress immune activity. The article also discusses the different types of immunotherapies, including cell-based immunotherapies, immunomodulators, vaccines, antibody-based targeted therapies, and oncolytic viruses. Additionally, it highlights the characteristics of an ideal immunomodulator and the limitations associated with these therapies. Monoclonal antibodies, both naked and conjugated, are explored as a specific type of immunotherapy, with examples of their use in treating various cancers. Furthermore, the article touches upon the classification and uses of immunosuppressive agents, particularly in organ transplantation, along with their adverse effects. Overall, this article provides a comprehensive overview of immunotherapy and its diverse applications in disease treatment.
... It can be categorized into three types: immunoglobulin E (IgE) mediated, non-IgE mediated, or mixed (6). IgE-mediated food allergy is typically characterized by exposure to very small amounts of allergic foods triggering clinical symptoms within minutes to hours after ingestion (5,7). In contrast, non-IgE mediated food allergy has a delayed onset of symptoms, often presenting chronically, making the association with the specific allergens obscure and challenging to diagnose (7). ...
... IgE-mediated food allergy is typically characterized by exposure to very small amounts of allergic foods triggering clinical symptoms within minutes to hours after ingestion (5,7). In contrast, non-IgE mediated food allergy has a delayed onset of symptoms, often presenting chronically, making the association with the specific allergens obscure and challenging to diagnose (7). Manifestations primarily include skin reactions (such as AD, contact dermatitis, and herpetiformis), respiratory reactions (such as Heinner syndrome), or gastrointestinal reactions such as eosinophilic esophagitis (EOE) (8). ...
Allergic diseases in children are major public health concerns due to their widespread and rising prevalence. Food-specific immunoglobulin G4(FS-IgG4) has been detected in patients with allergic diseases, but its clinical significance is still debated. In the present study, 407 children with allergic diseases were recruited and categorized into three groups according to the different systems involved: the respiratory system group, the skin system group, and a multiple system group, with the collection of clinical symptoms and serum antibodies, including total immunoglobulin E (IgE), house dust mite (HDM) IgE, food-specific IgE (FS-IgE), and FS-IgG4. Part of these patients were followed up with the intervention of FS-IgG4-guided diet elimination with or without add-on probiotics supplement. The analysis at baseline revealed distinct serum levels of different antibodies. The positive rate of FS-IgG4 in all groups was more than 80%, and the proportion of total IgE and FS-IgG4 both positive in the multi-system group was the highest (p=0.039). Egg and milk were the foods with the highest positive rate of FS-IgG4 in all groups. After diet elimination for more than 3 months, serum FS-IgG4 in children significantly decreased (P<0.05) along with the improvement of clinical symptoms, regardless of the add-on of probiotics. However, the intervention did not impact the serum levels of total IgE, FS-IgE, and HDM IgE. There was no further decrease of serum FS-IgG4 level in children followed up for more than 1 year, which may be related to noncompliance with diet elimination. Multivariate regression analysis revealed that the decline of serum FS-IgG4 was an independent predictable factor for the improvement of clinical symptoms (adjusted OR:1.412,95%CI 1.017–1.96, p=0.039). The add-on of probiotics showed less efficiency in reducing the FS-IgG4 level in more patients with relief of clinical symptoms. Our results confirmed the correlation between FS-IgG4 and allergic diseases, and the decreased FS-IgG4 could be a useful predictor for the improvement of allergic symptoms. FS-IgG4-guided diet elimination is an efficient treatment for allergic diseases. Our study adds solid data to the clinical significance of FS-IgG4 in allergic diseases.
