Search Results (133)

Background: Allergic rhinitis (AR) is a prevalent allergic disorder characterized by a complex pathogenesis. Drawing on traditional Chinese medicine theory and contemporary pharmacological principles, this study developed an inhalation-based herbal formulation, ZHW, to explore a novel non-invasive therapeutic approach. Objective: To investigate the therapeutic effects of ZHW on AR and elucidate its underlying mechanisms and potential targets through an integrated analysis of network pharmacology and proteomics. Materials and Methods: The volatile components of ZHW were analyzed by gas chromatography–mass spectrometry (GC-MS). The mouse model of AR was induced by OVA sensitization. The therapeutic efficacy of ZHW was assessed based on nasal symptom scores, histopathological examination, and inflammatory cytokine levels. Furthermore, the underlying mechanisms and potential targets of ZHW were investigated through integrated network pharmacology and proteomics analyses. Results: GC-MS analysis identified 39 bioactive compounds in ZHW. Inhalation treatment with ZHW demonstrated significant anti-allergic effects in OVA-sensitized mice, as evidenced by (1) reduced sneezing frequency and nasal rubbing behaviors; (2) decreased serum levels of IL-4, histamine, and OVA-specific IgE; (3) attenuated IL-4 concentrations in both nasal lavage fluid and lung tissue; (4) diminished nasal mucosal thickening; and (5) suppression of inflammatory cell infiltration. Integrated network pharmacology and proteomics analyses indicated that ZHW’s therapeutic effects were mediated through the modulation of multiple pathways, including the PI3K-Akt signaling pathway, the B cell receptor signaling pathway, oxidative phosphorylation, and the FcεRI signaling pathway. Key molecular targets involved Rac1, MAPK1, and SYK. Molecular docking simulations revealed strong binding affinities between ZHW’s primary bioactive constituents (linalool, levomenthol, linoleic acid, Linoelaidic acid, and n-Valeric acid cis-3-hexenyl ester) and these target proteins. Conclusions: The herbal formulation ZHW demonstrates significant efficacy in alleviating allergic rhinitis symptoms through multi-target modulation of key signaling pathways, including PI3K-Akt- and FcεRI-mediated inflammatory responses. These findings substantiate ZHW’s therapeutic potential as a novel, non-invasive treatment for AR and provide a strong basis for the development of new AR therapies. Future clinical development will require systematic safety evaluation to ensure optimal therapeutic outcomes. Full article

The aim of this systematic review was to evaluate the current evidence for the involvement of epithelial-derived extracellular vesicles (EVs) in Immunoglobulin E (IgE)-mediated allergic sensitisation. Original clinical and research studies specifically examining the effect of epithelial-derived EVs in IgE-mediated allergic sensitisation were included. Non-IgE mediated allergies, abstracts and review articles were excluded. A total of 18 publications were identified from three databases (EMBASE, Web of Science and PubMed) that indicate epithelial-derived EVs have the potential to promote tolerance or allergic sensitisation. For example, epithelial-derived EVs have the potential to promote IgE-mediated allergic sensitisation by delivering mRNAs that promote T helper 2 (Th2) polarisation and cytokine secretion, or promote tolerance through the induction of T regulatory (Treg) cells. The results also indicate that the potential role of epithelial-derived EVs in IgE-mediated allergic sensitisation may be dependent on the barrier, with all publications related to intestinal epithelium driving tolerance, but publications on nasal and bronchial/alveolar epithelia gaving mixed effects. No publications were found on cutaneous epithelia. Taken together, the literature suggests that epithelial-derived EVs play a key role in influencing IgE-mediated allergic sensitisation. Further research examining all epithelial barriers, using both robust human in vitro models that give more biologically relevant information, as well as clinical studies, are required to further characterise the role of epithelial-derived EVs in IgE-mediated allergic sensitisation. Full article

Background: Cow-milk-induced allergic proctocolitis (CMIAP) is a non-IgE-mediated food hypersensitivity that often resolves spontaneously but may predispose infants to IgE-mediated allergies and eosinophilic gastrointestinal disorders. Understanding its pathophysiology is crucial for microbiota-based interventions. Methods: We enrolled 32 exclusively breastfed infants—16 with confirmed cases of CMIAP and 16 age-matched healthy controls. The cohorts were sex-balanced (8 F/8 M), term-born (gestational age ± SD: 40 ± 1.2 vs. 39 ± 1.3 weeks), vaginally delivered, and sampled at a mean age of 2.0 ± 0.44 months (range 1.5–3.0) vs. 2.4 ± 0.66 months (range 1.5–3.5). Faecal samples underwent 16S rRNA gene sequencing on the Illumina NovaSeq platform, with diversity and differential abundance analyses. Results: The maternal dairy intake was similar (total dairy: 250 ± 80 vs. 240 ± 75 mL/day; yoghurt: 2.3 ± 1.0 vs. 2.5 ± 1.2 days/week; p = 0.72). Bray–Curtis dissimilarity assessments revealed distinct microbiota in infants with CMIAP. Infants with CMIAP had a lower abundance of Bifidobacterium (log₂FC−2.27; q = 0.022; ANCOM-BC), Collinsella (−29.35; padj < 0.0001; DESeq2), and Limosilactobacillus (−8.01; padj = 0.0285; DESeq2; q < 0.0001; ANCOM-BC) compared with controls. In contrast, Hungatella (+24.99; padj < 0.0001; DESeq2), Veillonella (+4.73; padj = 0.0221; DESeq2), Citrobacter (+10.44; padj = 0.0124; DESeq2), and Ruminococcus gnavus (+2.69; q < 0.0001; ANCOM–BC) were more abundant in the CMIAP group. Conclusions: Infants with CMIAP exhibit gut dysbiosis, which is characterised by the depletion of beneficial commensals and the enrichment of potential pathogens, independent of maternal dairy intake. Further studies should establish whether these microbiota alterations are causal or consequential in CMIAP. Full article

Background. Cow’s milk allergy (CMA) is one of the most common food allergies in infancy, with prevalence estimates of 0.5–7.5% in high-income countries. Data from low- and middle-income regions remain limited, and the predominant immune mechanism (IgE or non-IgE mediated) may vary across populations. Objective. We aimed to determine the prevalence and clinical characteristics of CMA in infants from an urban, low-income Chilean population. Methods. A prospective cohort study was conducted at Padre Hurtado Hospital in Santiago, Chile. Healthy term newborns were recruited and followed for up to 12 months. Sociodemographic, perinatal data and parental atopy were recorded. Parents were contacted monthly to screen for CMA symptoms. Infants with ≥two symptoms underwent clinical evaluation, a 4-week cow’s milk protein exclusion diet, and an open oral food challenge (OFC). Diagnosis followed international consensus guidelines. Results. Of 552 enrolled infants (48% male), 27 were diagnosed with CMA, yielding a prevalence of 4.9% (95% CI 3.1–7.0%). All cases exhibited non-IgE-mediated symptoms, including vomiting, dermatitis, colic, and perianal erythema. CMA was diagnosed before 6 months of age in 74% of cases. At 12 months, 40% had developed oral tolerance. Sociodemographic and perinatal characteristics were similar between groups, but some self-reported parental atopic traits were more frequent in CMA cases. Conclusions. CMA prevalence in this Chilean cohort was comparable to that reported in high-income countries, with a predominance of non-IgE-mediated forms. These findings support the need for standardized diagnostic protocols, including OFC, in diverse populations. Future studies should explore long-term outcomes and risk factors in non-IgE-mediated CMA. Full article

Background: The pathophysiology of non-IgE-mediated cow’s milk allergy is mostly unknown. Previous studies suggested a mechanism mediated by T cells, but this was not confirmed in subsequent studies. The aim of this study was to investigate the immunological mechanisms, especially the role of regulatory T cells (Tregs), in the pathophysiology of allergic proctocolitis (FPIAP). Methods: A prospective observational study was conducted on infants with FPIAP and a control group of healthy infants with similar ages. The main variables were lymphocyte populations, included Tregs, which were extracted from peripheral blood and processed immediately by flow cytometry at two time points: in the acute phase (“T0”) and after clinical resolution (“Tres”). Results: A total of 32 patients with FPIAP and 10 healthy infants were enrolled. There was a higher T-CD4 memory cell count, increased numbers of regulatory B cells and a higher percentage of Tregs (p < 0.01) in patients with acute FPIAP in contrast to the healthy group. The levels of granulocytes (mainly eosinophils), dendritic cells (mDC2) and NK16+56- cells were also significantly higher in the FPIAP group. NK16+56- cells and the number of granulocytes appeared to be the best markers for distinguishing between the healthy and FPIAP infants based on the ROC curves. Conclusions: FPIAP does not appear to have an immune mechanism mediated by T cells, but it may be associated with innate immunity responses characterized by an increase in NK16+56- cells, eosinophils and dendritic cells. These cells could be evaluated in future studies as possible markers of non-IgE-mediated cow’s milk protein allergy. Full article

Cow’s milk allergy is one of the most prevalent food allergies in infancy. Exclusive breastfeeding is the recommended source of nutrition for the first six months of life, but some infants may develop cow’s milk allergy due to the transfer of milk proteins such as β-lactoglobulin through breast milk. There are still many uncertainties about cow’s milk allergy in breastfed babies. The purpose of this review is to summarize the latest findings mainly focused on immunological mechanisms and challenges in diagnosis. We pointed out which clinical signs in breastfed infants are associated with immediate IgE responses and which are linked to delayed non-IgE mechanisms or mixed IgE/non-IgE-mediated reactions. Since standard IgE tests are often useless in non-IgE cases, diagnosis typically involves dietary elimination and cow’s milk challenge. This study addresses the controversial topic of maternal elimination diets, assessing the nutritional risks to both mothers and infants in relation to their possible benefits. It has also been discussed whether the microbiota signature could be a potential factor in both tolerance development and the risk of cow’s milk allergy in early life. Overall, accurate diagnosis and personalized treatment plans are vital to prevent overdiagnosis and ensure proper growth while maintaining the practice of breastfeeding. Full article

Background/Objectives: Food hypersensitivity remains an understudied and overlooked subject globally. It is characterized by adverse reactions to dietary substances, potentially triggered by various mechanisms. Food allergy, a subset of food hypersensitivity, denotes an immune response to food proteins categorized into immunoglobulin IgE-mediated or non-IgE-mediated reactions. Conversely, food intolerance, another facet of food hypersensitivity, refers to non-immunological reactions, in which the human body cannot properly digest certain foods or components, leading to gastrointestinal discomfort and other non-immune-related symptoms. The main objective of this study was to determine and differentiate the differences, characteristics, and types of food hypersensitivity. Methods: This study involved a comprehensive review of key research from 1990 onward, including review articles, prospective studies, nested case–control studies, and meta-analyses. Results: Recognizing these differences is essential for healthcare professionals to ensure accurate diagnosis, effective management, and improved patient outcomes, while also aiding dietitians in providing optimal nutritional and dietary guidance. Conclusions: there are big differences between the main characteristics, such as symptoms, complications, and treatments between allergies, and food intolerances. Commonly reported trigger foods include cow milk, gluten, eggs, nuts, and seafood. Full article

Peanut allergies, driven by sensitization to key allergens Ara h1, Ara h2, and Ara h3, present significant health risks, particularly in food processing and consumer settings where accidental exposure is frequent. To mitigate this risk, we developed AYA22AR321, a novel aptamer with selective, high-affinity binding to these allergens (Kd values: 0.5 nM for Ara h1, 14.5 nM for Ara h2, and 6.6 nM for crude peanut extract). Functional assays using RBL-2H3 (rat basophilic leukemia cell line) cells showed that AYA22AR321 significantly reduces IgE-mediated degranulation, indicating its potential to attenuate allergic responses. To translate these findings into practical use, we formulated an allergen-neutralizing spray, FISTOQ, containing AYA22AR321, which effectively neutralized peanut allergens on peanut-butter-contaminated surfaces. Stability tests confirmed that FISTOQ, comprising eco-friendly surfactant and preservative, maintains its allergen-neutralizing efficacy over time. Comprehensive safety assessments, including immunogenicity, cytotoxicity in human PBMCs, and mutagenicity via the Ames test, demonstrated that AYA22AR321 is non-immunogenic, non-cytotoxic, and non-mutagenic. This study establishes AYA22AR321 as a promising, targeted strategy for allergen control, providing a significant advancement in allergen mitigation and food safety for high-risk environments. Full article

Background: Food allergies are a growing global health concern, particularly among children, with no widely approved curative treatment beyond strict allergen avoidance. Oral immunotherapy (OIT) has emerged as a promising strategy to induce desensitization, yet its implementation is limited due to high rates of allergic reactions and patient non-compliance. Omalizumab, a monoclonal anti-IgE antibody, has been proposed as an adjunct to OIT to enhance safety and efficacy. Objective: This systematic review and meta-analysis aim to evaluate the efficacy and safety of omalizumab in combination with OIT for IgE-mediated food allergy in children. Methods: A systematic literature search was conducted in PubMed/MEDLINE and Cochrane Central databases to identify randomized controlled trials (RCTs), controlled clinical trials (CCTs), and observational studies assessing omalizumab as an adjunct to OIT in pediatric food allergy. Studies were evaluated for desensitization rates, immunological changes, adverse events, and quality-of-life improvements. Results: OIT combined with omalizumab led to significantly higher rates of desensitization, allowing patients to tolerate higher doses of allergens in a shorter timeframe compared to OIT alone. Omalizumab was associated with a reduction in adverse reactions, including anaphylaxis, and improved treatment adherence. However, the long-term sustainability of tolerance post-omalizumab discontinuation remains uncertain. Conclusions: Omalizumab facilitates rapid and effective desensitization in pediatric food allergy, enhancing the safety of OIT. Further research is needed to determine optimal treatment duration, long-term outcomes, and cost-effectiveness before widespread clinical adoption. Full article

Background/Objectives: Pediatric patients with non-IgE-mediated gastrointestinal food allergies (non-IgE-GIFAs) may experience alterations of nutritional status. This non-randomized, prospective intervention study investigated the impact of dietary counseling on nutritional status in pediatric patients with non-IgE-GIFAs. Methods: Patients of both sexes aged 0–14 years newly diagnosed with non-IgE-GIFAs received dietary counseling provided by certified pediatric dietitians immediately after diagnosis. Nutritional status parameters were assessed to identify nutritional status alterations at baseline and after 12 months of intervention (T12). Results: The study included 100 patients (58% male, mean age 8.5 ± 8.8 months). Non-IgE-GIFAs phenotypes included food protein-induced enteropathy (FPE, 44%), food protein-induced enterocolitis syndrome (FPIES, 11%), food protein-induced allergic proctocolitis (FPIAP, 17%), and food protein-induced motility disorders (FPIMD, 28%). At diagnosis, 1% was affected by obesity (1 FPIAP), 5% were affected by overweight (2 FPE, 1 FPIAP, and 2 FPIMD), 7% were moderately underweight (5 FPE and 2 FPIMD), 1% was severely underweight (1 FPE), 7% were moderately stunted (4 FPE, 1 FPIAP, and 2 FPIMD), 16% were moderately wasted (11 FPE, 1 FPIES, 1 FPIAP, and 3 FPIMD), and 4% were severely wasted (2 FPE and 2 FPIMD). At T12, improvements in anthropometric parameters were observed, along with a reduction in the prevalence of malnutrition by excess (6% at diagnosis vs. 2% at T12) and a reduction in the undernutrition subtypes rate, including underweight, stunting, and wasting (26% at diagnosis vs. 3% at T12, p < 0.001). Conclusions: Non-IgE-GIFAs can negatively impact the nutritional status of pediatric patients. Thus, dietary counseling could be an effective strategy for preventing and managing nutritional alterations in these patients. Full article

Peanut allergies affect millions of people worldwide, often causing life-threatening reactions and necessitating strict avoidance. Recent advancements in oral immunotherapy, such as Palforzia™, and IgE-mediated treatments (e.g., Xolair), have improved care options; however, their high costs limit accessibility and widespread utility. To address these challenges, researchers are employing conventional breeding and advanced molecular tools, such as CRISPR editing, to develop peanut lines with reduced levels of major allergenic proteins (Ara h1, Ara h2, Ara h3, and Ara h6). These reduced-immunogenicity genotypes retain their agronomic viability, flavor, and nutritional quality to some extent, offering the potential for cost-effective oral immunotherapy and safe food options for use in public spaces by non-allergic individuals. Rigorous evaluation, including immunological assays and human feeding trials, is essential to confirm their effectiveness in reducing allergic reactions. Adoption will depend on the establishment of clear regulatory guidelines, stakeholder education, and transparent communication of the benefits and risks. With sustained research, public trust, and supportive policies, reduced-immunogenicity peanuts could substantially lower the global burden of peanut allergies. This communication examined the impact of peanut allergies worldwide and explored strategies to develop peanut genotypes with reduced allergen content, including conventional breeding and advanced genetic engineering. It also addressed the challenges associated with these approaches, such as policy and regulatory hurdles, and outlined key requirements for their successful adoption by farmers and consumers. Full article

High-affinity IgE receptors (FcεRI) are expressed on human blood eosinophils and may be upregulated on eosinophils at sites of allergic inflammation including atopic dermatitis and allergic asthma. FcεRI engagement, however, fails to elicit “effector” responses from eosinophils. Thus, a functional role for FcεRI on eosinophils has been uncertain. We evaluated the role of FcεRI in enhancing eosinophil antigen presentation in vivo by using humanized FcεRI α chain (hFcεRIα) transgenic mice. Eosinophils from hFcεRIα transgenic mice expressed humanized FcεRIα, with higher levels of eosinophils from the bronchoalveolar lavage of experimental asthma than those from polymyxin-elicited peritoneal lavage. The hFcεRIα-bearing eosinophils instilled intratracheally (i.t.) into recipient wild-type mice migrated from airways into paratracheal lymph nodes (pLNs) and spleens. Eosinophils, pretreated in vitro with nitrophenyl-ovalbumin ((NP)-OVA) and anti-NP human IgE complexes and instilled i.t., presented NP antigen via hFcεRIα to T cells more effectively than those pretreated with NP-OVA only, as assessed by pLN cell proliferation. IgE/FcεRIα-facilitated eosinophil antigen presentation resulted in increased IL-4 but not INF-γ production by pLN cells, with a bias towards Th2 cytokine production. Furthermore, cross-linking hFcεRIα on eosinophils increased eosinophil expressions of T cell costimulatory proteins CD40, CD80, and CD86. Humanized FcεRIα on murine eosinophils functions to enhance eosinophil antigen presentation capacities by mediating IgE-facilitated antigen presentation and upregulating expression of requisite T cell costimulatory proteins. Thus, a functional, non-“effector” role for FcεRI on eosinophils is revealed through identifying a means by which IgE may act on eosinophils to mediate their immunomodulatory, enhanced antigen presentation capabilities. Full article

Eosinophilic esophagitis is a chronic, antigen-driven, immune-mediated disease characterized by esophageal dysfunction and significant eosinophilic infiltration. Its rising incidence and prevalence over recent decades reflect both increased clinical awareness and the influence of environmental factors such as dietary patterns and allergen exposure. Among food allergens, cow’s milk proteins are the most commonly implicated triggers, contributing to esophageal inflammation through complex immunological pathways involving both IgE-mediated and non-IgE-mediated mechanisms. Dietary elimination of cow’s milk has been shown to induce histologic remission in over 60% of pediatric patients, underscoring its pivotal role in eosinophilic esophagitis management. Despite these promising results, challenges persist, including variability in individual responses, the burden of adherence to restrictive diets, and gaps in understanding the molecular mechanisms driving cow’s milk-induced esophageal inflammation. This review examines the complex relationship between eosinophilic esophagitis and cow’s milk, focusing on its role in disease pathogenesis and management, offering insights into its therapeutic implications. Understanding the interplay between eosinophilic esophagitis and dietary allergens, particularly cow’s milk, may inform the development of targeted interventions and improve clinical outcomes for affected patients. Full article

Cow’s milk allergy (CMA) is the most common food allergy among children. An oral food challenge (OFC) remains a mainstay of the diagnosis of CMA, especially for the non-IgE-mediated type; however, this test can be risky and time-consuming. Hence, there is a need to identify biomarkers. Fecal calprotectin (FC) showed variable results, with good reliability and reproducibility in CMA patients. In this prospective study, we enrolled 76 children (aged 5–18 months) with CMA-related gastrointestinal and cutaneous symptoms following guidelines from the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. Clinical assessments included history, physical examination, skin prick tests, and IgE assays. FC levels and the Cow’s Milk Related Symptom Score (CoMiSS) were measured in 51 patients pre (T1) and post-diet (T2), with a subgroup analysis of 15 patients with elevated baseline FC (>50 mg/kg). The results showed that FC levels significantly decreased after the elimination diet (median: 30 mg/kg at T1, 16 mg/kg at T2; p < 0.01). In the subgroup with higher FC levels, median values dropped from 90 mg/kg to 33 mg/kg (p < 0.01). CoMiSS also improved (median: 8.50 at T1, 3.00 at T2; p < 0.01). Linear regression analysis showed no correlation between FC values and the CoMiSS at T1 and T2. In conclusion, the reduction in FC value after an elimination diet suggests that it could be considered a possible biomarker of bowel inflammation in CMA patients. Further studies are necessary to confirm these data and to evaluate and standardize the use of FC for diagnosis and follow-up of CMA. Full article

Background/Objectives: Food protein-induced allergic proctocolitis (FPIAP) is a non-IgE-mediated food allergy, usually presenting as bloody stools in breastfed, well-appearing, and regularly growing infants. The aim of our study was to describe the clinical features of Italian infants affected by FPIAP and their management and natural history in a real-life setting. Methods: A retrospective, observational study was performed at two tertiary pediatric hospitals (Florence and Trieste), including FPIAP-diagnosed infants between 2012 and 2022. Results: Most of the 100 enrolled patients were breastfed (68.0%), and the majority of those who underwent diagnostic tests (n = 51) showed normal hemoglobin and total IgE levels. A maternal elimination diet was performed in 69.0%, mostly for milk only, but 40.6% underwent multiple elimination diets. The remission rate was high both in breastfed infants (76.8%) and in those who received extensively hydrolyzed formula (81.8%). Nine subjects were left on a free diet, but six were lost at follow-up. The median time of complete remission was 30 days (IQR 14–60). Culprit food reintroduction was tolerated at a median age of 8 months (IQR 6–11), in ladder modality (for hen’s egg and cow’s milk) in 61.7%. Nine patients relapsed (14.3%) upon reintroduction with no associated variables identified at the regression analysis. The relapse rate was slightly higher when trigger food reintroduction was attempted > 12 months (16.7%) versus <12 months (13.0%). Conclusions: In our population, FPIAP had, as expected, a benign evolution. The early reintroduction of the suspect food in a gradual manner for cow’s milk and hen’s egg leads to good tolerance within the first year in most patients, avoiding unnecessary elimination diets. Full article