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PURPOSE OF REVIEW: The aim of this review is to highlight key published oral immunotherapy (OIT) protocols and post-desensitization strategies for the major food allergens and to cover important concepts to consider when evaluating OIT for food-allergic patients. Shared decision-making should help identify patient and family values which will help influence the type of evidence-based protocol and maintenance strategy to use. RECENT FINDINGS: With food OIT emerging as a treatment option, there is a pressing need for patients, physicians, and other providers to have a nuanced understanding of the management choices available to them. There are now randomized controlled trials (RCT) of OIT for peanut, egg, milk, and wheat, and reports of cohorts of patients who have undergone OIT for tree nuts and sesame clinically. The current published protocols contain significant diversity in terms of starting dose, build-up schedule, maintenance dose, and even the product used for desensitization. Emerging data can help direct the long-term maintenance strategy for patients on OIT. Based on patient and family values elicited through the shared decision-making process, an OIT protocol may be selected that balances the level of desensitization, potential side effects, frequency of clinic visits, and potential to induce sustained unresponsiveness, among other factors. Once maintenance dosing is reached, most patients will need to maintain regular exposure to the food allergen to remain desensitized. The option to transition to commercial food products with equivalent amounts of food protein as the OIT maintenance dose would simplify the dosing process and perhaps improve palatability as well. Less frequent or decreased OIT dosing can provide practical benefits but may affect the level of desensitization and safety for some patients.

Objective: Perfume (Parfum) or fragrance is a natural or synthetic cosmetic ingredient added to emit a pleasant aroma or to improve the odor of a cosmetic formula. It is a mixture of substances, not revealed by the manufacturer, which may contain ingredients with allergenic potential, endocrine disruptors, and other possible harmful effects on human health. This study aims to analyze children's cosmetics labels to assess the presence of Perfume. Methods: The researchers randomly visited points of sale in Curitiba, the capital of a southern Brazilian state; in order to catalog the largest possible number of children's cosmetics items. Results: 398 children's cosmetics were analyzed and found Parfum on 295 (74.1 %) of the labels, including 90.4 and 79,1 % of the shampoos and wet wipes, respectively. Conclusion: Exposure of children's skin to fragrances can lead to local side effects such as allergies, but also to systemic effects, and the lack of knowledge of the general population and health professionals about its possible deleterious effects emphasizes the importance of changes in the regulation of cosmetics aiming to reduce the use of this ingredient.

Resumen: El desarrollo y comercialización de los sensores de glucosa y las bombas de insulina han supuesto una revolución en el control de los pacientes diabéticos. En los últimos años se han detectado múltiples casos de dermatitis de contacto relacionados con estos dispositivos médicos, con el creciente interés sobre los alérgenos responsables de la sensibilización. Isobornil acrilato fue sin duda el alérgeno principal del dispositivo FreeStyle, motivando al fabricante a modificar la composición eliminando este alérgeno. Curiosamente, este alérgeno está presente en casi todos los sensores comercializados. La colofonia y derivados del ácido abiético desempeñan un papel relevante en cuanto al adhesivo. Recientemente aparecen nuevos componentes identificados como alérgenos, no comercializadas, como el dipropilene glicol diacrilato, la N,N-dimetilacrilamida, o el metacrilato de trietilenglicol, que están siendo foco de estudio. El impacto positivo que tiene el uso de estos dispositivos puede verse mermado por la sensibilización a uno de sus ingredientes, obligando en ocasiones a abandonar el dispositivo, y por ende, restando calidad de vida. El dermatólogo debe posicionarse respecto al estudio dirigido de estos pacientes, dando soporte a los servicios de endocrinología, con la finalidad de orientar tanto el cuidado de la piel como las alternativas posibles, especialmente con la colaboración de los fabricantes. Abstract: The development and commercialization of glucose sensors and insulin pumps has revolutionized the management of diabetes. These devices have been linked to multiple cases of contact dermatitis in recent years, however, giving rise to a growing interest in identifying the sensitizing allergens. Isobornyl acrylate was clearly identified as one of the main allergens responsible for contact dermatitis among users of the FreeStyle glucose sensor and was subsequently removed from the product ingredients. Remarkably, however, it is still used in most other sensors on the market. The common adhesive ingredients colophony and abietic acid derivatives have also been shown to be sensitizing agents. New components under study, such as dipropylene glycol diacrylate, N,N-dimethylacrylamide, and triethylene glycol methacrylate have recently been identified as allergens, though they are not commercially available for clinical testing. The benefits offered by glucose sensors and insulin pumps may be offset by sensitization to product ingredients, in some cases forcing discontinuation and diminishing quality of life. Dermatologists should play a role in this clinical and research scenario, offering case-by-case guidance to endocrinologists on skin care and possible alternatives for patients with glucose sensors and insulin pumps who develop contact dermatitis. They should also collaborate with the manufacturers developing these devices.

Background: Component‐resolved diagnosis allows detection of IgE sensitization having the advantage of reproducibility and standardization compared to crude extracts. The main disadvantage of the traditional allergen identification methods, 1‐ or 2‐dimensional western blotting and screening of expression cDNA libraries with patients' IgEs, is that the native structure of the protein is not necessarily maintained. Methods: We used a novel immunoprecipitation technique in combination with mass spectrometry to identify new allergens of Aspergillus fumigatus. Magnetic Dynabeads coupled with anti‐human IgE antibodies were used to purify human serum IgE and subsequently allergens from A. fumigatus protein extract. Results: Of the 184 proteins detected by subsequent mass peptide fingerprinting, a subset of 13 were recombinantly expressed and purified. In a panel of 52 A. fumigatus‐sensitized people with asthma, 23 non‐fungal‐sensitized asthmatics and 18 healthy individuals, only the former showed an IgE reaction by immunoblotting and/or ELISA. We discovered 11 proteins not yet described as A. fumigatus allergens, with fructose‐bisphosphate aldolase class II (FBA2) (33%), NAD‐dependent malate dehydrogenase (31%) and Cu/Zn superoxide dismutase (27%) being the most prevalent. With respect to these three allergens, native versus denatured protein assays indicated a better recognition of the native proteins. Seven of 11 allergens fulfilled the WHO/IUIS criteria and were accepted as new A. fumigatus allergens. Conclusion: In conclusion, we introduce a straightforward method of allergen identification from complex allergenic sources such as A. fumigatus by immunoprecipitation combined with mass spectrometry, which has the advantage over traditional methods of identifying allergens by maintaining the structure of the proteins. [ABSTRACT FROM AUTHOR]

Since the 1940s, patch tests in healthy volunteers (Human Predictive Patch Tests, HPPTs) have been used to identify chemicals that cause skin sensitization in humans. Recently, we reported the results of a major curation effort to support the development of OECD Guideline 497 on Defined Approaches (DAs) for skin sensitization (OECD in Guideline No. 497: Defined Approaches on Skin Sensitisation, 2021a. https://doi.org/10.1787/b92879a4-en). In the course of this work, we compiled and published a database of 2277 HPPT results for 1366 unique test substances (Strickland et al. in Arch Toxicol 97:2825–2837, 2023. https://doi.org/10.1007/s00204-023-03530-3). Here we report a detailed analysis of the value of HPPT data for classification of chemicals as skin sensitizers under the United Nations' Globally Harmonized System of Classification and Labelling of Chemicals (GHS). As a result, we propose the dose per skin area (DSA) used for classification by the GHS to be replaced by or complemented with a dose descriptor that may better reflect sensitization incidence [e.g., the DSA causing induction of sensitization in one individual (DSA1+) or the DSA leading to an incidence of induction in 5% of the tested individuals (DSA05)]. We also propose standardized concepts and workflows for assessing individual HPPT results, for integrating multiple HPPT results and for using them in concert with Local Lymph Node Assay (LLNA) data in a weight of evidence (WoE) assessment. Overall, our findings show that HPPT results are often not sufficient for deriving unambiguous classifications on their own. However, where they are, the resulting classifications are reliable and reproducible and can be integrated well with those from other skin sensitization data, such as the LLNA. [ABSTRACT FROM AUTHOR]

The global shrimp market holds substantial prominence within the food industry, registering a significant USD 24.7 billion in worldwide exportation in 2020. However, the production of a safe and high‐quality product requires consideration of various factors, including the potential for allergenic reactions, occurrences of foodborne outbreaks, and risks of spoilage. Additionally, the exploration of the recovery of bioactive compounds (e.g., astaxanthin [AX], polyunsaturated fatty acids, and polysaccharides) from shrimp waste demands focused attention. Within this framework, this review seeks to comprehend and assess the utilization of high‐intensity ultrasound (HIUS), both as a standalone method and combined with other technologies, within the shrimp industry. The objective is to evaluate its applications, limitations, and prospects, with a specific emphasis on delineating the impact of sonication parameters (e.g., power, time, and temperature) on various applications. This includes an examination of undesirable effects and identifying areas of interest for current and prospective research. HIUS has demonstrated promise in enhancing the extraction of bioactive compounds, such as AX, lipids, and chitin, while concurrently addressing concerns such as allergen reduction (e.g., tropomyosin), inactivation of pathogens (e.g., Vibrio parahaemolyticus), and quality improvement, manifesting in reduced melanosis scores and improved peelability. Nonetheless, potential impediments, particularly related to oxidation processes, especially those associated with lipids, pose a hindrance to its widespread implementation, potentially impacting texture properties. Consequently, further optimization studies remain imperative. Moreover, novel applications of sonication in shrimp processing, including brining, thawing, and drying, represent a promising avenue for expanding the utilization of HIUS in the shrimp industry. [ABSTRACT FROM AUTHOR]

Due to the widespread use of shellfish ingredients in food products, accurate food labelling is urgently needed for consumers with shellfish allergies. Most crustacean allergen detection systems target the immunorecognition of the allergenic protein tropomyosin. However, this mode of detection may be affected by an origin-dependent protein composition. This study determined if the geographic location of capture, or aquaculture, influenced the allergenic protein profiles of Black Tiger Shrimp (Penaeus monodon), one of the most farmed and consumed shrimp species worldwide. Protein composition was analysed in shrimp from nine different locations in the Asia–Pacific by SDS-PAGE, immunoblotting, and mass spectrometry. Ten of the twelve known shrimp allergens were detected, but with considerable differences between locations. Sarcoplasmic calcium-binding protein, myosin light chain, and tropomyosin were the most abundant allergens in all locations. Hemocyanin-specific antibodies could identify up to six different isoforms, depending on the location of origin. Similarly, tropomyosin abundance varied by up to 13 times between locations. These findings suggest that allergen abundance may be related to shrimp origin and, thus, shrimp origin might directly impact the readout of commercial crustacean allergen detection kits, most of which target tropomyosin, and this should be considered in food safety assessments. [ABSTRACT FROM AUTHOR]

Background: Interleukin (IL)-26 is produced by T helper type 17 (Type 17) cells and exerts immunomodulatory plus antimicrobial effects. Previous studies show that local IL-26 concentrations in the airways are higher in patients with uncontrolled than in those with controlled asthma, and that this intriguing cytokine bears biomarker potential. Here, we determined how systemic IL-26 relates to allergen sensitization, asthma severity, and to IL-17 A in children. Methods: Serum samples were obtained from children with (n = 60) and without (n = 17) sensitization to dog allergen, and IL-26 and IL-17 A protein concentrations were measured using ELISA. Self-reported history, including medication use and validated symptom-based questionnaire scores, was recorded. Results: The serum concentrations of IL-26 were enhanced in allergen-sensitized subjects and correlated with those of IL-17 A in a positive manner. However, the IL-26 concentrations did not markedly differ between allergen-sensitized subjects with and without asthma, eczema, allergic rhinitis, or a history of food allergy. Notably, IL-26 concentrations correlated with increasing Asthma Control Test (ACT) scores in a positive manner and with inhaled corticosteroid in a negative manner, amongst sensitized subjects with asthma. Moreover, subjects with asthma requiring ≥ 1 course of oral corticosteroids in the preceding 12 months had decreased IL-26 concentrations. Conclusion: This study forwards evidence that systemic IL-26, just like IL-17 A, is involved in allergen sensitization among children. The association of systemic IL-26 with improved asthma control is compatible with the cellular sources being recruited into the airways in severe asthma, which supports that this kinocidin bears potential as a biomarker and therapeutic target. [ABSTRACT FROM AUTHOR]

Sesame allergy is a serious public health problem and is mainly induced by IgE-mediated reactions, whose prevalence is distributed all over the world. Sesame has been included on the priority allergic food list in many countries. This review summarizes the mechanism and prevalence of sesame allergy. The characteristics, structures and epitopes of sesame allergens (Ses i 1 to Ses i 7) are included. Moreover, the detection methods for sesame allergens are evaluated, including nucleic-acid, immunoassays, mass spectrometry, and biosensors. Various processing techniques for reducing sesame allergenicity are discussed. Additionally, the potential cross-reactivity of sesame with other plant foods is assessed. It is found that the allergenicity of sesame is related to the structures and epitopes of sesame allergens. Immunoassays and mass spectrometry are the major analytical tools for detecting and quantifying sesame allergens in food. Limited technologies have been successfully used to reduce the antigenicity of sesame, involving microwave heating, high hydrostatic pressure, salt and pH treatment. More technologies for reducing the allergenicity of sesame should be widely investigated in future studies. The reduction of allergenicity in processed sesames should be ultimately confirmed by clinical studies. What's more, sesame may exhibit cross-reactivity with peanut and tree nuts. [ABSTRACT FROM AUTHOR]

In peanut allergy, Arachis hypogaea 2 (Ara h 2) and Arachis hypogaea 6 (Ara h 6) are two clinically relevant peanut allergens with known structural and sequence homology and demonstrated cross-reactivity. We have previously utilized X-ray crystallography and epitope binning to define the epitopes on Ara h 2. We aimed to quantitatively characterize the cross-reactivity between Ara h 2 and Ara h 6 on a molecular level using human monoclonal antibodies (mAbs) and structural characterization of allergenic epitopes. We utilized mAbs cloned from Ara h 2 positive single B cells isolated from peanut-allergic, oral immunotherapy–treated patients to quantitatively analyze cross-reactivity between recombinant Ara h 2 (rAra h 2) and Ara h 6 (rAra h 6) proteins using biolayer interferometry and indirect inhibitory ELISA. Molecular dynamics simulations assessed time-dependent motions and interactions in the antibody–antigen complexes. Three epitopes—conformational epitopes 1.1 and 3, and the sequential epitope KRELRNL/KRELMNL—are conserved between Ara h 2 and Ara h 6, while two more conformational and three sequential epitopes are not. Overall, mAb affinity was significantly lower to rAra h 6 than it was to rAra h 2. This difference in affinity was primarily due to increased dissociation of the antibodies from rAra h 6, a phenomenon explained by the higher conformational flexibility of the Ara h 6–antibody complexes in comparison to Ara h 2–antibody complexes. Our results further elucidate the cross-reactivity of peanut 2S albumins on a molecular level and support the clinical immunodominance of Ara h 2. We utilized monoclonal antibodies cloned from peanut-allergic, oral immunotherapy–treated patients to probe the cross-reactivity between clinically relevant peanut allergens Ara h 2 and Ara h 6 on a molecular level. Graphical Abstract [ABSTRACT FROM AUTHOR]

Background and Aim: Food/environmental allergens have been associated with eosinophilic esophagitis (EoE); however, the correlation between allergy profiles and disease responsiveness to proton pump inhibitor (PPI) therapy remains unclear. We aimed to assess the association between food/environmental allergies identified on allergen testing and histologic response to PPI in patients with treatment‐naive EoE. Methods: Adults with newly diagnosed EoE who underwent formal testing for food/environmental allergies at a tertiary center were included. All patients underwent twice‐daily PPI for 8 weeks with subsequent repeat endoscopy and biopsy to assess histologic response. Patients with <15 eosinophils/hpf on post‐PPI mucosal biopsies were classified as responders (PPI‐r‐EoE), while those with ≥15 eosinophils/hpf were nonresponders (PPI‐nr‐EoE). Results: Sixty‐one patients met inclusion criteria (21 PPI‐r‐EoE vs 40 PPI‐nr‐EoE). Demographic, clinical, and endoscopic finding variables were similar between groups. Positive food allergen test was more prevalent among PPI‐nr‐EoE patients (82.5% vs 42.9%, P = 0.003). On multivariable analysis, positive food allergen testing remained an independent predictor for PPI nonresponse (aOR 0.15, CI: 0.04–0.58, P = 0.0006). Positive environmental allergen testing was highly prevalent, with no significant differences between groups (77.5% vs 95.2%, P = 0.14). However, higher number of positive environmental allergens (23.3% [≥5 allergens] vs 73.3% [<5 allergens], P = 0.003) and specific aeroallergens correlated with PPI‐nr‐EoE. Conclusion: Positive food allergy testing and increased environmental allergens predicted lower likelihood of histologic response to PPI in EoE. Our findings support an allergic phenotype of EoE that may less likely respond to PPI therapy. Formal allergen testing may play a role in therapy selection and tailored management in EoE. [ABSTRACT FROM AUTHOR]

Background: Allergen immunotherapy (AIT)‐associated adverse events (AEs) limit its usage in the management of allergic diseases. The monoclonal anti‐IgE antibody (omalizumab) and AIT have complementary actions. However, no consensus has been reached on whether their combination could exert superior efficacy and safety. Objective: To evaluate whether the combination of AIT with omalizumab is superior to AIT alone in treating allergic diseases. Methods: The MEDLINE/PubMed, Embase, Scopus and Cochrane Library databases were searched to identify randomized control trials (RCTs) reporting the outcomes of omalizumab combined with AIT (omalizumab + AIT) versus AIT alone. A random‐effect model was established to estimate outcomes with a 95% confidence interval (CI). Results: A total of 11 eligible RCTs (involving 901 patients) were screened out for the meta‐analysis. According to a pooled analysis, omalizumab + AIT significantly increased the number of patients achieving the target maintenance dose (TMD) and sustained unresponsiveness (SU) to allergens (odds ratio [OR] = 2.43; 95% CI: 1.33–4.44; p = 0.004; I2 = 35%, and OR = 6.77; 95% CI: 2.10–21.80; p = 0.001; I2 = 36%, respectively). Similarly, individuals receiving the combination therapy reported significantly fewer episodes of severe systemic AEs than AIT alone (OR = 0.32; 95% CI: 0.18–0.59; p = 0.0003; I2 = 0%). Meanwhile, the improvements in symptom severity score (mean difference [MD] = −0.26), rescue medication daily means score (MD = −0.14), and number of patients consuming epinephrine in AIT (OR = 0.20) were all more evident than those in AIT alone. Conclusion: Omalizumab + AIT can significantly enhance the efficacy and safety of AIT by increasing TMD and SU to allergens, while decreasing severe systemic AEs. [ABSTRACT FROM AUTHOR]

Allergic rhinitis affects approximately 40% of children. This study aimed at determining the prevalence, sociodemographic features, comorbid illnesses, complications and quality of life in children referred to the outpatient clinic of "Allergic Rhinitis" in Penteli Children Hospital, Athens, Greece. We analyzed 590 pediatric patients referred to the outpatient clinic of "Allergic Rhinitis" in Penteli Children Hospital, Athens, Greece from 26/01/2012 to 20/11/2022. Allergic rhinitis was recorded as the one and only allergic disease in 59% of the children diagnosed with allergic rhinitis, concomitant asthma in 16% of them, atopic dermatitis in 8% and allergic conjunctivitis in 5%. 54% of asthmatic children was diagnosed allergic rhinitis, while 16% of allergic rhinitis children was diagnosed asthma. Skin tests were important diagnostic tools, not being necessary the measurement of total IgE in plasma. Eosinophils from nasal secretions were increased in 19% of the children with non-diagnostic cases and the diagnosis was local allergic rhinitis (LAR). Clinical presentations of allergic rhinitis were mainly nasal blockage, runny nose, recurrent sneezing and nasal itching. The most common complication was acute or chronic sinusitis 35%. Major associated comorbid illnesses among were tonsils hypertrophy, adenoid hypertrophy and inferior turbinate hypertrophy. Allergic rhinitis was reported in 78% of studied children and was frequently characterized by significant morbidity. Allergic rhinitis affected all paediatric age group and was peaked at age group 11–14 years and 5–7 years. There were associated epidemiological features, clinical manifestations, comorbid illnesses, complications and affectation of the quality of life in children. [ABSTRACT FROM AUTHOR]

Meniere's Disease is a rare ear disorder that can cause severe morbidity to the patient and has no definitive treatment to date. Endolymphatic hydrops is the critical event. Though symptomatology is well understood, the exact etiology of Endolymphatic hydrops attack is still unclear. Twenty-five consecutive patients of Meniere's Disease diagnosed in the Vertigo clinic aged 12 to 70 years were included. Their allergic status was evaluated using a skin prick test. Allergic and non-allergic patients were then identified. Comparison between the two groups was made to identify the effect of allergy on the severity of symptoms using vertigo scales, Functional level scale, Dizziness handicap index, and Pure tone average staging. The prevalence of allergy among Meniere's Disease patients was 56%. The most common allergen found in our study was tyrophagus(n = 8). Polysensitization was more common(n = 12). Airborne allergens were more common than food allergens. There was no significant relationship between the severity scales and the allergen positivity status (p > 0.05). The prevalence of allergy is more among patients with Meniere's Disease. The Endolymphatic sac is allergy prone. The occurrence of endolymphatic hydrops may be due to a cross-reaction of allergen-induced IgE antibodies to self-antigen. Management of the specific allergen may help decrease symptomatology in these patients. Allergen-specific therapies have a promising role in the treatment of allergic conditions and provide a long-term symptom-free period in affected individuals. This can be applied in patients with Meniere's Disease having associated allergic features based on their skin prick test results. [ABSTRACT FROM AUTHOR]

This article discusses the development of a potential treatment for shrimp allergy using hypoallergenic chimeric virus-like particles (VLPs). The VLPs were designed to display the major shrimp allergen, Pen m 1, and were shown to elicit blocking IgG antibody responses. The VLPs exhibited reduced allergenicity compared to the soluble form of Pen m 1 and induced a Th1-biased immune response in mice. Further research is needed to investigate the reactogenicity and therapeutic capacity of the VLPs in animal models of shrimp allergy. The study was funded by various organizations and the authors declare no conflict of interest. [Extracted from the article]

Cosmetic products are chemical substances or mixtures used on the skin, hair, nails, teeth, and the mucous membranes of the oral cavity, whose use is intended to clean, protect, correct body odor, perfume, keep in good condition, or change appearance. The analysis of cosmetic ingredients is often challenging because of their huge complexity and their adulteration. Among various analytical tools, mass spectrometry (MS) has been largely used for compound detection, ingredient screening, quality control, detection of product authenticity, and health risk evaluation. This work is focused on the MS applications in detecting and quantification of some common cosmetic ingredients, i.e., preservatives, dyes, heavy metals, allergens, and bioconjugates in various matrices (leave-on or rinse-off cosmetic products). As a global view, MS-based analysis of bioconjugates is a narrow field, and LC- and GC/GC×GC-MS are widely used for the investigation of preservatives, dyes, and fragrances, while inductively coupled plasma (ICP)-MS is ideal for comprehensive analysis of heavy metals. Ambient ionization approaches and advanced separation methods (i.e., convergence chromatography (UPC2)) coupled to MS have been proven to be an excellent choice for the analysis of scented allergens. At the same time, the current paper explores the challenges of MS-based analysis for cosmetic safety studies. [ABSTRACT FROM AUTHOR]

Atopic dermatitis, or eczema, is the most common chronic skin disorder, characterized by red and pruritic lesions. Its etiology is multifaceted, involving an interplay of factors, such as the allergic immune response, skin barrier dysfunction, and dysbiosis of the skin microbiota. Recent studies have explored the role of extracellular vesicles (EVs), which are lipid bilayer-delimitated particles released by all cells, in atopic dermatitis. Examination of the available literature identified that most studies investigated EVs released by Staphylococcus aureus, which were found to impact the skin barrier and promote the release of cytokines that contribute to atopic dermatitis development. In addition, EVs released by the skin fungus, Malassezia sympodialis, were found to contain allergens, suggesting a potential contribution to allergic sensitization via the skin. The final major finding was the role of EVs released by mast cells, which were capable of activating various immune cells and attenuating the allergic response. While research in this area is still in its infancy, the studies examined in this review provide encouraging insights into how EVs released from a variety of cells play a role in both contributing to and protecting against atopic dermatitis. [ABSTRACT FROM AUTHOR]

The hazel allergen Cor a 1 is a PR-10 protein, closely related to the major birch pollen allergen Bet v 1. Hazel allergies are caused by cross-reactive IgE antibodies originally directed against Bet v 1. Despite the importance of PR-10 proteins in allergy development, their function and localization in the plant remain largely elusive. Therefore, the presence of Cor a 1 mRNA and proteins was investigated in different tissues, i.e., the female flower, immature and mature nuts, catkins, and pollen. Four yet unknown Cor a 1 isoallergens, i.e., Cor a 1.0501–1.0801, and one new Cor a 1.03 variant were discovered and characterized. Depending on the isoallergen, the occurrence and level of mRNA expression varied in different tissues, suggesting different functions. Interestingly, Cor a 1.04 previously thought to be only present in nuts, was also detected in catkins and pollen. The corresponding Cor a 1 genes were expressed in Escherichia coli. The purified proteins were analysed by CD and NMR spectroscopy. Immunoblots and ELISAs to determine their allergenic potential showed that the new proteins reacted positively with sera from patients allergic to birch, hazel and elder pollen and were recognized as novel isoallergens/variants by the WHO/IUIS Allergen Nomenclature Sub-Committee. [ABSTRACT FROM AUTHOR]

Asthma is one of the most common non-communicable diseases, and its prevalence and morbidity are influenced by a wide array of factors that are only partially understood. In addition to individual predisposition linked to genetic background and early life infections, environmental factors are crucial in determining the impact of asthma both on an individual patient and on a population level. Several studies have examined the role of the environment where asthmatic subjects live in the pathogenesis of asthma. This review aims to investigate the differences in the prevalence and characteristics of asthma between the pediatric population residing at higher altitudes and children living at lower altitudes, trying to define factors that potentially determine such differences. For this purpose, we reviewed articles from the literature concerning observational studies assessing the prevalence of pediatric asthma in these populations and its characteristics, such as spirometric and laboratory parameters and associated sensitization to aeroallergens. Despite the heterogeneity of the environments examined, the hypothesis of a beneficial effect of residing at a higher altitude on the prevalence of pediatric asthma could be confirmed, as well as a good profile on airway inflammation in asthmatic children. However, the possibility of a higher hospitalization risk for asthma in children living at higher altitudes was demonstrated. Moreover, a positive association between residing at a higher altitude and sensitization to pollens and between lower altitude and sensitization to house dust mites could be confirmed in some pediatric patients, even if the results are not homogeneous, probably due to the different geographical and climatic regions considered. Nonetheless, further studies, e.g., extensive and international works, need to be conducted to better understand the complex interplay between different environmental factors, such as altitude, and the pathogenesis of asthma and how its prevalence and characteristics could vary due to climate change. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Anti‐IgE immunotherapy with monoclonal antibodies represents a breakthrough in treatment of severe allergic diseases. However, drawbacks such as short half‐life and high price are not negligible. Our objective is to develop an anti‐IgE vaccine based on virus‐like particles (VLPs) which can induce long‐lasting neutralizing IgG anti‐IgE antibodies reducing allergic responses without causing intrinsic mast cell activation due to IgE cross‐linking.The vaccines were made by chemically coupling three synthetic mouse IgE‐Fc fragments to plant‐derived immunologically optimized CuMVTT VLPs. The immunogenicity of the vaccines was tested by immunizing naive or allergic mice either with the coupled vaccines or the VLP control followed by systemic or local allergen challenge.Mice immunized with the vaccines exhibited high titers of anti‐IgE antibodies in the sera and high levels of anti‐IgE secreting plasma cells in lymphoid organs. Moreover, free IgE in serum were reduced by the induced anti‐IgE antibodies; therefore, less IgE was bound to FcεRI on the surface of basophils. In line with these reduced IgE levels on effector cells after vaccination, immunized mice were protected from challenge with allergens. Importantly, despite presence of anti‐IgE antibodies, no signs of acute or chronic allergic response were seen in immunized allergic mice.The generated vaccines can effectively induce anti‐IgE antibodies that did not cause allergic responses in sensitized mice but were able to decrease the level of free and cell bound IgE and protected sensitized animals from allergic responses upon allergen challenge. [ABSTRACT FROM AUTHOR]

Imported allergens are involved in many allergic reactions, with unexpected and unusual implications. They can be involved in developing asthma, allergic rhinoconjunctivitis, Hymenoptera venom allergies and food allergies. Imported allergens can be implied in respiratory allergies attributable to commercial practices and accidental diffusion through air currents that have introduced non-native species in new geographical contexts. Ambrosia artemisiifolia L., a plant native to North America and currently in the western part of Lombardy, represents an example. Moreover, a variation in the pollen concentration in the Northwest Tuscany area and Trentino Alto-Adige was observed. Cannabis sativa is another imported allergen used frequently by adolescents. Regarding potential imported food allergens, there is no validated list. Imported food allergens derive from ethnic foods, referring to Mexican/Latin American, Chinese/Japanese, Southeast Asian, Arab/Middle Eastern and African cuisine. Four insect flours were recently introduced to the European and Italian markets (Acheta domesticus, Alphitobius diaperinus, Tenebrio molitor and Locusta migratoria). The association between the accidental introduction through commercial traffic, climate change, and the absence of natural enemies in the destination ecosystem is related to the introduction of a specific Hymenoptera, Vespa velutina, in Italy and Europe. External events attributable to human activities, such as climate change and the introduction of non-native plants, foods and Hymenoptera through trade, have contributed to the issue of imported allergens. Making the correct diagnosis and guiding the diagnostic and therapeutic path in this particular context represent the concerns of the pediatric allergist. [ABSTRACT FROM AUTHOR]

Background: Facial contact dermatitis is an emerging skin disorder due to the use of a large array of materials over the face. It leads to psychological distress in patients, impacting their quality of life. Most of the allergens applied over the face vary as per cosmetic or herbal products' availability, usage, or religious practices. Identifying and discontinuing the implicated allergens will lead to a better prognosis and reduced morbidity in clinical practice. Objectives: To determine the frequency of different allergens responsible for causing facial contact dermatitis, in an urban part of central India, using patch test with the help of Indian standard and cosmetic series. Materials and Methods: All suspected patients (>18 years) of facial contact dermatitis visiting the outpatient department of dermatology were patch tested with both Indian standard and cosmetic series. Results: Out of 38/58 patch-test-positive patients, 71.06% were females, and 28.94% were males. Most patch-test-positive females were housewives. The most common allergens implicated were thiomersal (17.24%), followed by fragrance mix (15.51%), and paraphenylene diamine (12.06%). Conclusion: In our study, forehead and malar areas were most commonly involved indicating fairness creams and perfumes as the important contributors to facial contact dermatitis. Antigen batteries need to be updated with changing social and cultural trends, as many with a consistent history of aggravation with some products tested negative in patch tests. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of 6‐phytase produced by the genetically modified strain Aspergillus oryzae DSM 33737 (HiPhorius™ 10, 40, 20L and 50L) as a zootechnical feed additive for all poultry, all Suidae and all fin fish. The FEEDAP Panel concluded that the genetic modification of the production strain does not give rise to safety concerns. Based on the no observed adverse effect level identified in a subchronic oral toxicity study in rats, the additive was considered safe for all poultry, all Suidae and all fin fish at the proposed conditions of use. The Panel also concluded that the use of the product as a feed additive is of no concern for the consumers and the environment. The liquid formulations of the additive are not skin or eye irritants. The two solid ones are not skin irritants but are eye irritants. Owing to the lack of data, the Panel cannot conclude on the skin sensitisation of the final formulations of the additive. Due to the proteinaceous nature of the active substance (6‐phytase), the additive is considered a respiratory sensitiser. The Panel concludes that the additive is efficacious when included in the diet of poultry for fattening or reared for laying/breeding, reproductive Suidae, and all fin fish. Due to the lack of sufficient data, the Panel could not conclude on the efficacy for laying and reproductive poultry and growing Suidae. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on Bacillus velezensis ATCC PTA‐6737 as a zootechnical additive (functional group: gut‐flora stabiliser) in the context of the renewal of the authorisation for turkeys for fattening and turkeys reared for breeding. The applicant is also requesting to modify the target species in the current authorisations to 'all growing poultry', the increase of the recommended use level in chickens for fattening, chickens reared for laying and minor poultry species except minor poultry for laying from 1 × 107 to 1 × 108 CFU/kg complete feed and the compatibility of the additive with halofuginone. The applicant provided evidence that the additive currently in the market complies with the conditions of the authorisation. There was no new evidence that would lead to reconsider previous conclusions. Therefore, the FEEDAP Panel concluded that the additive remains safe for all poultry species for fattening and reared for laying/breeding, the consumers and the environment under the current authorised conditions of use. The additive is not irritant to the skin and eyes, but it should be considered a respiratory sensitiser. The Panel could not conclude on the skin sensitisation potential of the additive. The Panel concluded that the additive has a potential to be efficacious as a zootechnical additive for poultry for fattening and reared for laying/breeding under the proposed conditions of use. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of authorisation of sodium bisulphate (SBS) as a feed additive for all terrestrial animal species (category: technological additive; functional group: preservative), and for all terrestrial animal species other than cats, mink, pets and other non‐food‐producing animals (category: technological additive; functional group: acidity regulator). EFSA has also been asked to assess the new use of the product as an acidity regulator and flavouring compound in all pets and other non‐food‐producing animals except aquatic animals. The applicant provided evidence that the additive currently in the market complies with the existing conditions of authorisation. There is no evidence that would lead the FEEDAP Panel to reconsider its previous conclusions. Thus, the Panel concluded that the additive remains safe for all terrestrial animal species, consumer and the environment under the authorised conditions of use. The FEEDAP Panel considers that the proposed new use would not introduce risks not already considered in the previous assessment and therefore the same conclusions on all terrestrial animal species, consumers of products from animals fed the additive and the environment would apply. Regarding user safety, the additive is irritant to the skin, eyes and the respiratory tract, and should be considered a skin and respiratory sensitiser. There is no need to assess the efficacy of the additive in the context of the renewal of the authorisation. The Panel considers that the additive has the potential to be efficacious as an acidity regulator and sensory additive (flavouring compound) in feed for pet and non‐food‐producing animals (except aquatic animals). [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of Huvezym® neXo 100 G/L, a product containing endo‐1,4‐β‐xylanase, endo‐1,4‐β‐glucanase and xyloglucan‐specific‐endo‐β‐1,4‐glucanase activities produced by a non‐genetically modified strain of Trichoderma citrinoviride (DSM 33578), as a zootechnical additive for all Suidae. The applicant provided information confirming the taxonomic identification of the production strain. The batches used for the characterisation of the final formulations showed compliance with the minimum specifications of the additive in terms of enzyme activities (> 15,000 EPU, > 1000 CU, > 1000 XGU per g) but not for the ratio of the enzymes, which is lower (ca. 7:1:1) than the ones specified (15:1:1). The Panel could not conclude on the representativeness of the test item used in the toxicological and tolerance studies with respect to the final formulations. Therefore, the conclusions are limited to the product with a minimum enzyme activity of 15,000 EPU, 1000 CU, 1000 XGU per g and a xylanase:glucanase:xyloglucanase ratio of 15:1:1. The Panel concluded that the additive is safe for the target species, consumers and the environment. Huvezym® neXo 100 G is not an irritant to the skin and eyes but should be considered a skin sensitiser. Huvezym® neXo 100 L is neither an irritant to the skin and eyes nor a skin sensitiser. Due to the proteinaceous nature of the active substances, the additive is considered a respiratory sensitiser. The additive has the potential to be efficacious in all reproductive Suidae at the minimum proposed use level. Owing to the lack of sufficient data, the Panel could not conclude on the efficacy of the additive for Suidae for fattening or reared for reproduction. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of monensin sodium (Coxidin®) as a coccidiostat for chickens for fattening, chickens reared for laying, turkeys for fattening and turkeys reared for breeding. The additive currently on the market complies with the existing conditions of authorisation. The FEEDAP Panel concluded that Coxidin® remains safe for turkeys for fattening (up to 16 weeks) and extends this conclusion to turkeys reared for breeding (up to 16 weeks). The Panel was not in the position to confirm that the current maximum authorised level of 125 mg monensin sodium/kg complete feed remains safe for chickens for fattening and chickens reared for laying. The use of monensin sodium from Coxidin® at the corresponding maximum authorised/proposed use levels in the target species is safe for the consumer. The existing maximum residue levels (MRLs) for poultry tissues ensure consumer safety. No withdrawal time is necessary. Both formulations of Coxidin® pose a risk by inhalation. The formulation with wheat bran as a carrier was neither irritant to the skin nor a skin sensitiser but it was irritant to the eyes. In the absence of data, no conclusions could be made on the potential of the formulation containing calcium carbonate to be irritant to skin and eyes and to be a skin sensitiser. The use of monensin sodium from Coxidin® in complete feed for the target species poses no risk for the terrestrial compartments and for sediment. No risk for groundwater is expected. For chickens for fattening the risk for aquatic compartment cannot be excluded, but no risks are expected for the other animal categories. There is no risk of secondary poisoning. Coxidin® is efficacious in controlling coccidiosis at a level of 100 mg/kg complete feed for chickens for fattening and at 60 mg/kg complete feed for turkeys for fattening. These conclusions are extended to chickens reared for laying and turkeys reared for breeding. The Panel noted that there are signs of development of resistance of Eimeria spp. to monensin sodium. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of the authorisation of Cylactin® as a zootechnical feed additive for cats and dogs. The active agent of the additive is Enterococcus lactis NCIMB 10415 and the micro‐encapsulated formulation, Cylactin® LBC ME5 PET, was assessed. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. The Panel concluded that the additive remains safe for cats and dogs. Regarding user safety, the additive was not shown to be skin and eye irritant, but it should be considered a respiratory sensitiser. No conclusions can be drawn on the skin sensitisation. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of Enterococcus lactis DSM 22502 as a technological feed additive for all animal species. The applicant provided evidence that the additive currently on the market complies with the existing conditions of authorisation. There is no new evidence that would lead the FEEDAP Panel to reconsider its previous conclusions regarding the safety and efficacy of the additive. The FEEDAP Panel concluded that E. lactis remains safe for all animal species, consumers and environment under the authorised conditions of use. Regarding the user safety, the Panel concluded that the additive is not irritating to the skin or eyes. No conclusions can be drawn on the potential of the additive to cause skin sensitisation, but it is considered to be a respiratory sensitiser. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation. [ABSTRACT FROM AUTHOR]

Much evidence supports that the early introduction of allergenic foods in weaning is useful to prevent food allergies later in life. Real life is often different, with factors related to mothers and infants. Our study aimed to deepen the timing of introducing the foods responsible for most allergic reactions during the weaning and why parents delay their introduction. 110 mothers participated in the study, compiling a questionnaire. Exclusive breastfeeding was associated with a delayed introduction of allergenic foods at 4 months (r = 0.433, p < 0.01) and 1 year (r = 0.486, p < 0.01). Large-for-gestational age at birth was inversely associated with a delayed introduction of allergenic foods (r=-0.204, p < 0.05). This study demonstrates that introducing many allergens is delayed during the weaning. Parents with infants fed with exclusive breastfeeding could need more information about the correct time of introduction of potential allergens in the weaning. [ABSTRACT FROM AUTHOR]

Up to a third of the world's population suffers from allergies, yet the effectiveness of available preventative measures remains, at large, poor. Consequently, the development of successful prophylactic strategies for the induction of tolerance against allergens is crucial. In proof-of-concept studies, our laboratory has previously shown that the transfer of autologous hematopoietic stem cells (HSC) or autologous B cells expressing a major grass pollen allergen, Phl p 5, induces robust tolerance in mice. However, eventual clinical translation would require safe allergen expression without the need for retroviral transduction. Therefore, we aimed to chemically couple Phl p 5 to the surface of leukocytes and tested their ability to induce tolerance. Phl p 5 was coupled by two separate techniques, either by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) or by linkage via a lipophilic anchor, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol)-maleimide (DSPE-PEG-Mal). The effectiveness was assessed in fresh and cultured Phl p 5-coupled cells by flow cytometry, image cytometry, and immunofluorescence microscopy. Chemical coupling of Phl p 5 using EDC was robust but was followed by rapid apoptosis. DSPE-PEG-Mal-mediated linkage was also strong, but antigen levels declined due to antigen internalization. Cells coupled with Phl p 5 by either method were transferred into autologous mice. While administration of EDC-coupled splenocytes together with short course immunosuppression initially reduced Phl p 5-specific antibody levels to a moderate degree, both methods did not induce sustained tolerance towards Phl p 5 upon several subcutaneous immunizations with the allergen. Overall, our results demonstrate the successful chemical linkage of an allergen to leukocytes using two separate techniques, eliminating the risks of genetic modifications. More durable surface expression still needs to be achieved for use in prophylactic cell therapy protocols. [ABSTRACT FROM AUTHOR]

The present study aimed to separate, identify, and characterise the degradation products formed when mavacamten is exposed to stress degradation as well as the stability of the drug in various environments and also to understand its degradation chemistry. Prediction of in silico toxicity and mutagenicity was aimed at the observed degradation products. Stress degradation along with stability studies and degradation kinetics were performed on mavacamten, and separation of degradation products was carried out by high‐performance liquid chromatography. Tandem mass spectrometry studies were executed to characterise the structures of degradation products using product ion fragments. Orthogonally, nuclear magnetic resonance experiments were conducted to elucidate the structures having ambiguity in characterising them. Deductive Estimation of Risk from Existing Knowledge and Structure Activity Relationship Analysis using Hypotheses software were used to establish in silico toxicity and mutagenic profiles of mavacamten and its degradation products. Two degradation products of mavacamten found in acidic hydrolytic stress conditions were separated, identified, characterised, and proposed as 1‐isopropylpyrimidine‐2,4,6(1H,3H,5H)‐trione and 1‐phenylethanamine. Mavacamten was found to be stable under different pH and gastrointestinal conditions. The degradation kinetics of mavacamten under 1 N acidic condition followed zero‐order kinetics, and it was degraded completely within 6 h. In silico toxicity and mutagenicity studies revealed that 1‐phenylethanamine can be a skin sensitiser. A high‐performance liquid chromatography method was developed for the separation of degradation products of mavacamten and characterised by liquid chromatography–tandem mass spectrometry and nuclear magnetic resonance. During the manufacturing and storage of drug product, precautions need to be taken when dealing with acidic solutions as the drug is prone to hydrolysis in acidic conditions. The formation of 1‐phenylethanamine under these conditions is to be monitored as it is a skin sensitiser. [ABSTRACT FROM AUTHOR]

Background Pigmented contact dermatitis (PCD) is a noneczematous form of allergic contact dermatitis characterized by dermal hyperpigmentation. Allergen avoidance is the cornerstone of therapy, but it is difficult to achieve. The use of immunosuppressives seems rational, but data are lacking. Objectives To compare outcomes with azathioprine (AZA), leflunomide and allergen avoidance (AA) in patients with PCD. Methods A comparative study was conducted on 28 patients with patch test-positive PCD who were randomly allocated to one of three treatment groups: AZA 2 mg kg–1 daily for 24 weeks + AA (n = 10); leflunomide (LEF) 20 mg daily for 24 weeks + -AA (n = 8); AA alone (n = 10). Patients were followed up for an additional 24 weeks. The Dermal Pigmentation Area and Severity Index (DPASI) score and Hindi Melasma Quality of Life scale (MELASQOL) were used to assess hyperpigmentation and quality of life (QoL). respectively. Results Hair colorants (n = 12) and paraphenylenediamine (n = 8) were the most common allergens. Mean (SD) DPASI score decreased from 30.97 (3.69), 32.35 (3.90) and 31.86 (3.47) to 13.78 (4.25), 21.67 (2.99) and 20.64 (3.82) at 48 weeks in the three groups, respectively (P < 0.001); the maximum percentage decline was seen with AZA (56%). Mean (SD) MELASQOL score was reduced in the three treatment groups from 48.0 (6.46), 46.75 (3.69) and 46.6 (4.65) to 19.6 (6.98), 24.5 (5.80) and 24.0 (5.49), respectively, at 48 weeks (P < 0.001). Reductions in DPASI and Hindi MELASQOL scores were significantly correlated. The most frequent adverse event was transaminitis in both the AZA and LEF groups. Conclusions Patients on AZA achieved a statistically significantly greater reduction in DPASI and MELASQOL score; therefore, AZA may fulfil an unmet need in PCD treatment. An objective reduction in hyperpigmentation was paralleled by an improvement in QoL score, reiterating the need for active management of this disease. [ABSTRACT FROM AUTHOR]

Background: Monitoring of adverse events induced by cosmetics performed by health authorities, known as cosmetovigilance, has been relied on the collection of case notifications. Objectives: We aimed to show how a contact dermatitis registry can contribute to the cosmetovigilance of emerging allergens. We used the example of phenylethyl resorcinol, an infrequent allergen with only 6 previous cases reported in Europe and Japan since 2013. Methods: A systematic search in the Spanish Registry of Contact Dermatitis and Cutaneous Allergy (REIDAC) database was performed to identify patients with positive patch test to phenylethyl resorcinol or cosmetics that contains it between June 2018 and January 2023. We collected the main clinical features of these patients and compared them with those of patients recorded in the registry with similar epidemiological features. Results: Thirteen patients with positive patch test to phenylethyl resorcinol were identified. All the patients were women with a mean age of 42 years (range 32–59) and their lesions were mainly in the face. Conclusion: Assessing the importance of infrequent allergens based solely on a case series is difficult. Multicentre registries facilitate the collection of cases and provide appropriate background information for new allergens. [ABSTRACT FROM AUTHOR]

While oral desensitization is capable of alleviating peanut allergen anaphylaxis, long-term immune tolerance is the sought-after goal. We developed a liver-targeting lipid nanoparticle (LNP) platform to deliver mRNA-encoded peanut allergen epitopes to liver sinusoidal endothelial cells (LSECs), which function as robust tolerogenic antigen-presenting cells that induce FoxP3+ regulatory T-cells (Tregs). The mRNA strand was constructed by including nucleotide sequences encoding for nonallergenic MHC-II binding T-cell epitopes, identified in the dominant peanut allergen, Ara h2. These epitopes were inserted in the mRNA strand downstream of an MHC-II targeting sequence, further endowed in vitro with 5 and 3 capping sequences, a PolyA tail, and uridine substitution. Codon-optimized mRNA was used for microfluidics synthesis of LNPs with an ionizable cationic lipid, also decorated with a lipid-anchored mannose ligand for LSEC targeting. Biodistribution to the liver was confirmed by in vivo imaging, while ELISpot assays demonstrated an increase in IL-10-producing Tregs in the spleen. Prophylactic administration of tandem-repeat or a combination of encapsulated Ara h2 epitopes induced robust tolerogenic effects in C3H/HeJ mice, sensitized to and subsequently challenged with crude peanut allergen extract. In addition to alleviating physical manifestations of anaphylaxis, there was suppression of Th2-mediated cytokine production, IgE synthesis, and mast cell release, accompanied by increased IL-10 and TGF-β production in the peritoneum. Similar efficacy was demonstrated during LNP administration postsensitization. While nondecorated particles had lesser but significant effects, PolyA/LNP-Man lacked protective effects. These results demonstrate an exciting application of mRNA/LNP for treatment of food allergen anaphylaxis, with the promise to be widely applicable to the allergy field.

Allergens are substances that cause abnormal immune responses and can originate from various sources. IgE-mediated allergies are one of the most common and severe types of allergies, affecting more than 20% of the population in Western countries. Allergens can be subdivided into a limited number of families based on their structure, but this does not necessarily indicate the origin or the route of administration of the allergen, nor is the molecular basis of allergenicity clearly understood. This review examines how understanding the allergenicity of proteins involves their structural characterization and elucidates the study of conformational diversity by nuclear magnetic resonance spectroscopy. This article also discusses allergen cross-reactivity and the mechanisms by which IgE antibodies recognize and bind to allergens based on their conformational and linear epitopes. In addition, we outline how the pH, the proteolytic susceptibility and the endosomal degradation affect the outcome of allergic reactions, and how this is correlated with conformational changes and secondary structure rearrangement events. We want to emphasize the importance of considering structural diversity and dynamics, proteolytic susceptibility and pH-dependent factors to fully comprehend allergenicity.

Background and Aim: Considering the need to perform a food challenge test in suspected food allergy cases, the purpose of this study was to investigate the results of the open oral food challenge (OFC) test in children with allergies and compare its results with their skin prick test (SPT). Materials and Methods: In this descriptive, cross-sectional, retrospective study, we reviewed the records of 63 allergic children with a positive SPT to cow milk, egg, or wheat, who had referred to the allergy and immunology subspecialty clinic in Kashan, Iran. The patients with positive SPT for the studied allergens, received complete allergen restriction diet for 3 months. After 3 months, open OFC test was performed according to the protocol. Data were analyzed using descriptive statistics and inferential statistics (Chi-square test to investigate the relationship between the response type in OFC and qualitative variables). Results: The mean age of the children was 6.46±3.14 years and more than half of them were girls. Most children were allergic to cow milk (54%). 25.4% of allergic children responded negatively to the open OFC test. 26.5%, 29.4%, and 16.7% of the children who were allergic to cow milk, egg, or wheat, respectively, responded negatively to the open OFC test, and these differences were not statistically significant. In all three food allergen groups, skin-mucosal symptoms were the most common finding which was indicative of a positive response to the open OFC test. Conclusion: The open OFC test results in children with a positive SPT to cow milk, egg or wheat indicated a relatively high failure rate of the test in the children. We recommend attention to food sensitivities in the evaluation of these patients. After confirmation of food sensitivities by existing methods; it is necessary to prevent consumption of these allergens and observe safety tips when dealing with these allergens

Asthma is a common chronic respiratory disease exacerbated by multiple environmental factors. Acute ozone exposure has previously been implicated in airway inflammation, airway hyperreactivity, and other characteristics of asthma, which may be attributable to altered sphingolipid metabolism. This study tested the hypothesis that acute ozone exposure alters sphingolipid metabolism within the lung, which contributes to exacerbations in characteristics of asthma in allergen-sensitized mice. Adult male and female BALB/c mice were sensitized intranasally to house dust mite (HDM) allergen on days 1, 3, and 5 and challenged on days 12-14. Mice were exposed to ozone following each HDM challenge for 6 h/day. Bronchoalveolar lavage, lung lobes, and microdissected lung airways were collected for metabolomics analysis (N = 8/sex/group). Another subset of mice underwent methacholine challenge using a forced oscillation technique to measure airway resistance (N = 6/sex/group). Combined HDM and ozone exposure in male mice synergistically increased airway hyperreactivity that was not observed in females and was accompanied by increased airway inflammation and eosinophilia relative to control mice. Importantly, glycosphingolipids were significantly increased following combined HDM and ozone exposure relative to controls in both male and female airways, which was also associated with both airway resistance and eosinophilia. However, 15 glycosphingolipid species were increased in females compared with only 6 in males, which was concomitant with significant associations between glycosphingolipids and airway resistance that ranged from R2 = 0.33-0.51 for females and R2 = 0.20-0.34 in male mice. These observed sex differences demonstrate that glycosphingolipids potentially serve to mitigate exacerbations in characteristics of allergic asthma.

Mast cells originate from the CD34+/CD117+ hematopoietic progenitors in the bone marrow, migrate into circulation, and ultimately mature and reside in peripheral tissues. Microbiota/metabolites and certain immune cells (e.g., Treg cells) play a key role in maintaining immune tolerance. Cross-linking of allergen-specific IgE on mast cells activates the high-affinity membrane-bound receptor FcεRI, thereby initiating an intracellular signal cascade, leading to degranulation and release of pro-inflammatory mediators. The intracellular signal transduction is intricately regulated by various kinases, transcription factors, and cytokines. Importantly, multiple signal components in the FcεRI-mast cell-mediated allergic cascade can be targeted for therapeutic purposes. Pharmacological interventions that include therapeutic antibodies against IgE, FcεRI, and cytokines as well as inhibitors/activators of several key intracellular signaling molecues have been used to inhibit allergic reactions. Other factors that are not part of the signal pathway but can enhance an individuals susceptibility to allergen stimulation are referred to as cofactors. Herein, we provide a mechanistic overview of the FcεRI-mast cell-mediated allergic signaling. This will broaden our scope and visions on specific preventive and therapeutic strategies for the clinical management of mast cell-associated hypersensitivity reactions.

Introduction: Raising the numbers of patch testing in suspected children increases the rate of diagnosis of allergic contact dermatitis and the identification of clinically relevant allergens. Objective: The aim of this study to identify the most frequently observed allergens among Turkish children and adolescents patch tested in 2013-2023. Methods: The patch test results of 160 patients (age ≤18) were analyzed retrospectively. The frequency of contact allergens and distribution of positive results in terms of gender, age group (children and adolescents), and the presence of atopic dermatitis (AD) were identified. Results: Forty-nine patients (30.6%), 34 girls and 15 boys, exhibited positive patch test reactions to a minimum of one allergen, and contact sensitivity was statistically significant higher in girls (P=0.034). The 5 most frequent allergens were nickel sulfate (10.6%), methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) (8.1%), cobalt chloride (5.6%), p-phenylenediamine (PPD) (5%), and MI (3.5%). No significant association was observed between patch test positivity and age groups (p>.05). Nickel sulfate sensitivity was significantly higher in girls than boys (P=.043). A positive reaction was detected in 31.3% of patients with AD and in 33.7% of those without (P>.05) and a significant relationship was observed between contact sensitivity to fragrance allergens and AD (P=.046). Conclusion: Metals and preservatives represent the most frequent allergens in Turkish children and adolescents. Metal sensitivity is expected to decrease as legislation is enforced. Regulatory measures are now required to reduce MI and MCI/MI contact allergy in Turkey.

Anaphylaxis is a rare but well-known cause of sudden unexpected death, although data from forensic autopsies in anaphylactic deaths are limited. Herein, a retrospective study of a series of allergic deaths from 2009 through 2019 in Shanghai, China, was conducted to investigate the demographic, medical, and forensic pathological characteristics of fatal anaphylaxis to improve medicolegal understanding on anaphylactic death. Sixty-two autopsy cases of anaphylactic death were registered in this study. Males dominated the cases (74.2%) against females (25.8%), with an average age of 38.8 years. Medications (98.4%), particularly antibiotics (72.6%), were the most frequent cause of anaphylaxis, and 44 cases (71.0%) occurred in clinics administered illegally by unlicensed clinicians. The anaphylactic symptoms began within a few minutes to less than 1 h in 53 cases, with dyspnea (56.5%) and sudden shock (46.8%) being the most common clinical signs. Thirty cases (48.4%) of anaphylaxis resulted in death within 1 h. Laryngeal edema and multiple tissue eosinophil infiltration (85.5%) were the most prevalent autopsy findings, followed by pulmonary edema and congestion (24.2%), which were considered to be non-specific but suggestive. The comorbidities were mainly cardiovascular disease (33.9%), pneumonia (8.1%) and asthma (8.1%). Serum IgE were measured in 11 of 62 cases, ranging from 43.3 to 591 IU/ml, severed as a helpful marker. Therefore, we suggested a thorough analysis of allergen exposure, clinical history and autopsy findings is required for the diagnosis of anaphylactic death currently.

Allergens originated from Salsola kali (Russian thistle) pollen grains are one of the most important sources of aeroallergens causing pollinosis in desert and semi-desert regions. T-cell epitope-based vaccines (TEV) are more effective among different therapeutic approaches developed to alleviate allergic diseases. The physicochemical properties, and B as well as T cell epitopes of Sal k 1 (a major allergen of S. kali) were predicted using immunoinformatic tools. A TEV was constructed using the linkers EAAAK, GPGPG and the most suitable CD4+ T cell epitopes. RS04 adjuvant was added as a TLR4 agonist to the amino (N) and carboxyl (C) terminus of the TEV protein. The secondary and tertiary structures, solubility, allergenicity, toxicity, stability, physicochemical properties, docking with immune receptors, BLASTp against the human and microbiota proteomes, and in silico cloning of the designed TEV were assessed using immunoinformatic analyses. Two CD4+ T cell epitopes of Sal k1 that had high affinity with different alleles of MHC-II were selected and used in the TEV. The molecular docking of the TEV with HLADRB1, and TLR4 showed TEV strong interactions and stable binding pose to these receptors. Moreover, the codon optimized TEV sequence was cloned between NcoI and XhoI restriction sites of pET-28a(+) expression plasmid. The designed TEV can be used as a promising candidate in allergen-specific immunotherapy against S. kali. Nonetheless, effectiveness of this vaccine should be validated through immunological bioassays. [ABSTRACT FROM AUTHOR]

This study is nationwide multicenter epidemiological research, aimed at investigating the distribution changes and seasonal patterns of various airborne allergens among preschool children with allergic rhinitis (AR) in different regions of China, and analyzing the clinical correlation between sensitization to various airborne allergens and AR symptoms in children. Information on children was collected through standard questionnaires, and total IgE (tIgE) and specific IgE (sIgE) for 11 inhalant allergens were tested. The results showed that dust mites are the primary allergens for preschool AR children (39%). Among pollen allergens, Amb a had the highest positivity rate (8.1%), followed by Art v (7.8%). The sensitization rates for two mites peaked in May (46.9% and 40.6%). Art v peaked in August (21.5%), while Amb a had peaks in May (12.7%) and August (17.8%). The sensitization peaks for various tree pollens mainly occurred in August. In the Eastern monsoon region, the sensitization rate to mites was significantly higher than in the Northwest arid and semi-arid regions; whereas, for pollen allergens, the sensitization rates to Amb a, Pla a, Pin a, Pop d, and Bet v were significantly higher in the Northwest arid and semi-arid regions than in the Eastern monsoon region. The correlation among various tree pollens, specifically between Pla a, Pin r, Pop d, and Bet v was strong (0.63 ~ 0.79), with a cross-overlapping percentage of 53.9%. Children with multiple pollen sensitizations had higher cumulative nasal symptom scores than those negative for pollen (P < 0.01). Children with only pollen sensitization had higher cumulative rhinitis symptom scores than the all-negative group (P < 0.0001) and the mite-only sensitization group [P < 0.05], while the mite-only sensitization group also had higher scores than the all-negative group [P < 0.05], and the group sensitized to both pollen and mites had lower scores than the pollen-only group [P < 0.05]. This study indicates that sensitization to mites and grass pollens exhibits significant regional differences, with grass pollen allergies primarily occurring in autumn, sensitization to pollens in general exhibits a pronounced seasonal pattern. Moreover, pollen sensitization aggravates nasal and ocular symptoms in AR children. [ABSTRACT FROM AUTHOR]

Many baby cleansers are promoted as hypoallergic products; however, these claims are not typically validated. This study assessed the 50 best‐selling baby cleansers from online retailer Amazon for potential allergens. We found that the presence of most marketing claims, including “hypoallergenic” or “allergy‐tested,” did not correlate with the number of potential allergens in a cleanser. Furthermore, the total number of marketing claims of a cleanser was positively correlated with the number of allergens, highlighting the discordance between marketing claims and allergen content in baby cleansers. [ABSTRACT FROM AUTHOR]

Importance: An estimated 7.6% of children and 10.8% of adults have IgE-mediated food-protein allergies in the US. IgE-mediated food allergies may cause anaphylaxis and death. A delayed, IgE-mediated allergic response to the food-carbohydrate galactose-α-1,3-galactose (alpha-gal) in mammalian meat affects an estimated 96 000 to 450 000 individuals in the US and is currently a leading cause of food-related anaphylaxis in adults. Observations: In the US, 9 foods account for more than 90% of IgE-mediated food allergies—crustacean shellfish, dairy, peanut, tree nuts, fin fish, egg, wheat, soy, and sesame. Peanut is the leading food-related cause of fatal and near-fatal anaphylaxis in the US, followed by tree nuts and shellfish. The fatality rate from anaphylaxis due to food in the US is estimated to be 0.04 per million per year. Alpha-gal syndrome, which is associated with tick bites, is a rising cause of IgE-mediated food anaphylaxis. The seroprevalence of sensitization to alpha-gal ranges from 20% to 31% in the southeastern US. Self-injectable epinephrine is the first-line treatment for food-related anaphylaxis. The cornerstone of IgE-food allergy management is avoidance of the culprit food allergen. There are emerging immunotherapies to desensitize to one or more foods, with one current US Food and Drug Administration–approved oral immunotherapy product for treatment of peanut allergy. Conclusions and Relevance: IgE-mediated food allergies, including delayed IgE-mediated allergic responses to red meat in alpha-gal syndrome, are common in the US, and may cause anaphylaxis and rarely, death. IgE-mediated anaphylaxis to food requires prompt treatment with epinephrine injection. Both food-protein allergy and alpha-gal syndrome management require avoiding allergenic foods, whereas alpha-gal syndrome also requires avoiding tick bites. This clinical review summarizes the epidemiology, pathophysiology, clinical presentation, prevention, diagnosis, and management of IgE-mediated food allergy and anaphylaxis to food proteins and food glycans. [ABSTRACT FROM AUTHOR]

Background: Tropical pulmonary eosinophilia (TPE) is a chronic respiratory syndrome associated with Lymphatic Filariasis (LF), a tropical parasitic infection of the human, transmitted by mosquitoes. The larval form of LF (microfilariae) are trapped in the lungs of TPE subjects have a major role in initiating the TPE syndrome. To date, there are no reports on the potential allergen that is responsible for generating parasite-specific IgE in TPE. Methodology/Principal findings: In this project, we screened a cDNA expression library of the microfilarial stages of Wuchereria bancrofti with monoclonal IgE antibodies prepared from subjects with clinical filarial infections. Our studies identified a novel molecule that showed significant sequence similarity to an allergen. A blast analysis showed the presence of similar proteins in a number of nematodes parasites. Thus, we named this molecule as Nematode Pan Allergen (NPA). Subsequent functional analysis showed that NPA is a potent allergen that can cause release of histamine from mast cells, induce secretion of proinflammatory cytokines from alveolar macrophages and promote accumulation of eosinophils in the tissue, all of which occur in TPE lungs. Conclusions/Significance: Based on our results, we conclude that the NPA protein secreted by the microfilariae of W. bancrofti may play a significant role in the pathology of TPE syndrome in LF infected individuals. Further studies on this molecule can help design an approach to neutralize the NPA in an attempt to reduce the pathology associated with TPE in LF infected subjects. Author summary: Lymphatic filariasis, commonly called as elephantiasis is a gruesome disfiguring disease caused by parasitic worms. Some of the infected individuals develop asthma like hypersensitivity reaction called Tropical Pulmonary Eosinophilia (TPE), which can be fatal. TPE is believed to be caused by allergens released by the larval (microfilariae) stages of the lymphatic filarial worms in the lung blood vessels. However, no potential allergen have been described to date that is responsible for causing the TPE symptoms. In this study we screened a phage display cDNA expression library of the microfilariae stages of the lymphatic filarial parasite with IgE monoclonal antibodies prepared from subjects with lymphatic filarial infections, some of these individuals also exhibited TPE clinical symptoms. This approach identified a novel nematode specific pan allergen (NPA). When tested in the laboratory, NPA showed that it can trigger histamine release from mast cells, trigger inflammatory responses in lung cells and can cause accumulation of eosinophils in the tissue. All these are typical clinical symptoms of TPE. Thus, we conclude in this study that targeting the NPA can be a potential treatment option for alleviating the allergy and hypersensitivity reactions such as in TPE during parasitic infections. [ABSTRACT FROM AUTHOR]

Objective •This study aims to assess the correlation between allergic conjunctivitis (AC) and allergic rhinitis (AR). Methods • A total of 462 patients diagnosed with either allergic conjunctivitis or allergic rhinitis and treated at our hospital from January 2018 to December 2020 were included. Patients were categorized into two groups, the AC group and the AR group, based on their initial department of consultation. The AC group comprised 232 patients diagnosed with allergic conjunctivitis in the ophthalmology department, while the AR group consisted of 230 patients diagnosed with allergic rhinitis in the ENT department. Allergen analysis was conducted on patients presenting with both AC and AR and conjunctival and nasal mucosal scrapings were performed to examine eosinophil presence. The study analyzed the association between allergic AC and AR. Results • In the AC group, 174 patients (75.00%) had concurrent AR, while in the AR group, 169 patients (73.48%) had concurrent AC. Inhalant allergen testing among patients with concurrent AC and AR revealed that the primary inhalant allergens were dust mites, house dust, and fungi, with specific immunoglobulin E (IgE) positivity of 91.23%. Testing for food allergens identified fish, shrimp, and crab as ingestive allergens, with a specific IgE positivity of 58.58%. Eosinophil presence was assessed through conjunctival and nasal mucosal scrapings in patients with concurrent AC and AR. Eosinophils were detected in 188 cases (54.81%) through conjunctival scraping and 197 cases (57.43%) through nasal mucosal scraping, with no significant differences observed (P > .05). Conclusions • AC and AR share a common pathophysiological process and allergen profile, with the conjunctiva and nasal mucosa serving as sites of allergic reactions. This study suggests the integration of AC prevention and treatment into AR prevention strategies. [ABSTRACT FROM AUTHOR]