Detecting IgE sensitizations in the serum of allergic dogs is commonly done using allergen extracts, but these are difficult to standardize. This article details the development and validation of the Pet Allergy Xplorer (PAX; Nextmune, Stockholm, Sweden), the first multiplex macroarray for the detection of IgE sensitization in dogs using allergen extracts and molecular components; the PAX is derived from the Allergy Xplorer (ALEX2; MacroArray Diagnostics, Vienna, Austria). The selection of allergens, cartridge processing, strategy for identifying and blocking IgE directed against cross-reactive carbohydrate determinants (CCD), and the method used for determining the positivity threshold are described. The validation of the PAX included evaluations of the specificity of its anti-IgE monoclonal antibody, specificity of IgE binding to target allergens, assay precision, and internal consistency. Additionally, the influence of possible confounding factors, such as sample type, the influence of hemolysis, lipemia, bilirubinemia, and elevated CCD-IgE, was tested. Finally, the sensitization rates of 23,858 European dogs to 145 environmental and Hymenoptera venom allergens were summarized. The PAX is accurate and reproducible and has a unique CCD-detection and blocking strategy; its molecular allergens offer a unique window on allergen cross-reactivity.

In vitro tests of cellular activity form part of the diagnostic algorithm of drug hypersensitivity reactions. Because of the wide range of pharmacological mechanisms, clinical symptoms, genetic components and laboratory tests, it is important to know how a particular test performs in the diagnostic procedure. We carried out the detailed retrospective analysis of more than 6,000 measurements of numerous drug compounds tested in the past 6 years. Our cell viability-based lymphocyte transformation had a coefficient of variation of 10% and showed similar performance over the whole range of tested ages. With an adequate number of parallel measurements, the test can identify modest increases in stimulation indices with high confidence. Similar percentages of analytically positive responses were observed for the three most frequently tested drug groups, namely antibiotics, non-steroid anti-inflammatory agents and anesthetics. These results confirm that cell viability tests are suitable alternatives of proliferation assays in drug allergy testing.

IgE-mediated wheat allergy is a gluten-related disorder. Wheat is one of the five most common food allergens in children. However, the natural history of IgE-mediated wheat allergy has seldom been described in the research literature. This study presents the current state of knowledge about the IgE-mediated wheat allergy in children.

In this review, special emphasis will be placed on red grape polyphenols for their anti-oxidant and anti-inflammatory activities. Therefore, their capacity to inhibit major pathways responsible for activation of oxidative systems and expression and release of pro-inflammatory cytokines and chemokines will be discussed. Furthermore, regulation of immune cells by polyphenols will be illustrated with special reference to the activation of T regulatory cells which support a tolerogenic pathway at intestinal level. Furthermore, the effects of red grape polyphenols will be analyzed in obesity, as a low grade systemic inflammation. Also, possible modifications of inflammatory bowel disease biomarkers and clinical course have been studied upon polyphenol administration, either in animal models or in clinical trials. Moreover, the ability of polyphenols to cross the blood-brain barrier has been exploited to investigate their neuroprotective properties. In cancer, polyphenols seem to exert several beneficial effects, even if conflicting data are reported about their influence on T regulatory cells. Finally, the effects of polyphenols have been evaluated in experimental models of allergy and autoimmune diseases. Conclusively, red grape polyphenols are endowed with a great anti-oxidant and anti-inflammatory potential but some issues, such as polyphenol bioavailability, activity of metabolites and interaction with microbiota, deserve deeper studies.

Seafood is a vital source of nutrients, and its consumption has grown globally. Shellfish is a major cause of food allergy and anaphylaxis worldwide, affecting an estimated 0.5-2.5% of the general population. Most basic and clinical research has traditionally focused on crustaceans, leaving the characteristics of mollusk allergy poorly understood. In the Canary Islands, limpets (sea gastropod) are commonly consumed as part of the local cuisine. While some cases of limpet allergy have been reported, there are no published studies featuring large series or detailed clinical analyses of this specific food allergy. A cohort of patients with sensitization to limpet were studied: 66 were monosensitized to limpets (group A), while 64 were also sensitized to other shellfish (group B). Limpet ingestion caused delayed and severe symptoms. In group A, only 11,5% of patients showed positive shellfish allergen detection, compared to 67,9% in group B. The presence of protein bands in the 25-40 and 50-200 kDa range in monosensitized patients distinguishes our study from another researchs. Our study presents the largest reported series of patients with limpet allergy to date. The aim is to analyze the clinical and immunological characteristics of a local sample of limpet-allergic patients, contributing to a better understanding of this emerging condition.

Hazelnut is a widespread nut species, especially in Europe, that can be consumed raw or roasted, due to its pleasant taste and nutritional properties. Despite the renowned beneficial properties, hazelnuts contain several proteins capable of inducing food allergy in sensitized individuals such as Cor a 2 (profilin), Cor a 8 (lipid transfer protein), Cor a 9 (11S seed storage globulin, legumin-like) and Cor a 11 (7S seed storage globulin, vicilin-like). In the present paper we investigated the effectiveness of autoclave based treatments in decreasing the allergic potential of hazelnut as also assessed by submitting the treated material to in vivo skin prick test and to in vitro immunoblot analysis with sera of allergic individuals exposed to the treated food material. This preliminary analysis shows that autoclave treatment, preceded by hydration and/or followed by drying, seems to be a promising approach and appears to be effective in reducing the allergenicity of hazelnut in most patients, probably due to the denaturation of most major and minor allergenic proteins. This work will open to the opportunity to produce, in perspective, hypoallergenic hazelnut derivatives tolerated by the allergic subjects.

All allergic responses to food indicate failure of immunological tolerance but it is unclear why cow’s milk and egg (CME) allergies resolve more readily than reactivity to peanuts (PN). We sought to identify differences between PN and CME allergies through constitutive immune status and responses to cognate and non-cognate food antigens. Children with confirmed allergy to CME (n=6), PN (n=18) non-allergic (NA) (n=8) controls were studied. Constitutive secretion of cytokines was tested in plasma and unstimulated mononuclear cell (PBMNC) cultures. Blood dendritic cell (DC) subsets were analyzed alongside changes in phenotypes and soluble molecules in allergen stimulated MNC cultures with or without cytokine neutralization. We observed that in allergic children constitutively high plasma levels IL-1β, IL-2, IL-4, IL-5 and IL-10 but less IL-12p70 than in non-allergic children was accompanied by spontaneous secretion of sCD23, IL-1β, IL-2 IL-4, IL-5, IL-10, IL-12p70, IFN- and TNF- in MNC cultures. Furthermore, blood DC subset counts differed in food allergy. Antigen-presenting cell phenotypic abnormalities were accompanied by higher B and T cell percentages with more Bcl-2 within CD69+ subsets. Cells were generally refractory to antigenic stimulation in vitro but IL-4 neutralization led to CD152 downregulation by CD4+ T cells from PN allergic children responding to PN allergens. Canonical discriminant analyses segregated non-allergic and allergic children by their cytokine secretion patterns, revealing differences and areas of overlap between PN and CME allergies. Despite an absence of recent allergen exposure, indication of in vivo activation, in vitro responses independent of challenging antigen and the presence of unusual costimulatory molecules suggest dysregulated immunity in food allergy. Most important, higher Bcl-2 content within key effector cells implies survival advantage with potential to mount abnormal responses that may give rise to the manifestations of allergy. Here, we put forward the hypothesis that the lack of apoptosis of key immune cell types might be central to the development of food allergic reactions.

Most fungal species are commensals, not pathogenic for plants, humans, or animals. However, several species from genera Alternaria, Aspergillus, Trichophyton and Microsporum are common causes of disease, even for immunocompetent individuals, contributing to skin barrier impairment. A total of 68 allergic dogs were selected from a veterinary dermatology and allergy outpatient consultation, for conditions related to Malassezia overgrowth or other fungal complications. Allergy diagnosis was made through anamnestic and clinical criteria and allergy-implicated species were identified by intradermal testing (IDT) and serum determination of specific immunoglobulin E (sIgE). Dermatophagoides farinae, Dactylis glomerata and Malassezia pachydermatis showed as the higher sensitization species from each group. Significant correlations at p<0.05 were found between Dactylis glomerata and Phleum pratense grass pollens, Dermatophagoides farinae and Dermatophagoides pteronyssinus, Acarus siro, Tyrophagus putrescentiae and Lepidoglyphus destructor dust/storage mites, and between fungi like Aspergillus mix and Penicillium or Alternaria alternata. A significant correlation was also found between sensitization to Aspergillus mix and D. farinae, D. pteronyssinus or A. siro. Rather severe dermatitis was observed where positive IDT to Malassezia pachydermatis was found, regardless of the presence of circulating sIgE, allowing us to perceive the usefulness of both sIgE and IDT for allergy diagnosis to fungi.

Several animal food allergens assembly into amyloids under gastric-like environments. These aggregated structures provide Gad m 1 with an enhanced IgE interaction due to the amyloid assembly of the epitope regions. However, whether these properties are unique of Gad m 1 or common to other food allergens has not yet been addressed. Using Bos d 5, Bos d 12 and Gal d 2 as food allergen models and Gad m 1 as control, aggregation reactions and the sera of milk, egg and fish allergic patients we have analyzed the IgE interaction of the distinct amyloids. We found that amyloids formed by Bos d 12 and Gal d 2 full-length and truncated chains are recognized by the IgEs of milk and egg allergic patient sera. As with Gad m 1, in most cases amyloid recognition is higher than that of the precursor structure. Bos d 5 was not recognized under any fold by the IgE of the sera studied. These results support that formation of IgE-binding amyloids might be a common feature to animal food allergen.

Allergic diseases are becoming a major healthcare issue in many developed nations, where living environment and lifestyle are most predominantly distinct. Such differences include urbanized, industrialized living environments, overused hygiene products, antibiotics, stationary lifestyle, and fast-food based diets tend to reduce microbial diversity and lead to impared immune protection, which further increase the development of allergic diseases. In the same time, studies also showed that modulating microbiomes can ameliorate allergic symptoms. Therefore, in this paper, we aimed to review recent findings on the potential role of the human microbiome in the gastrointestinal tract, surface of skin and respiratory tract for the development of allergic diseases. Furthermore, we addressed a potential therapeutic or even preventive strategy for such allergic diseases by modulating the human microbial composition.

This study evaluated the anti-inflammatory effects, protection of gut barrier integrity, and stimulation of phagocytosis in peripheral cells of a nutritional supplement based on a synergistic combination of yeast-based ingredients with a unique 1,3/1,6-glucan complex and a consortium of postbiotic Saccharomyces cerevisiae rich in selenium and zinc. The anti-inflammatory effect in Caco-2 cells in the presence and absence of a pro-inflammatory challenge (tumour necrosis factor alpha [TNF-α]/interferon gamma [IFN-ɣ]) showed statistically significant reductions of IFN-ɣ induced protein-10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) levels vs. controls (p &lt; 0.001). Disruption of the gut integrity in the presence or absence of Escherichia coli (ETEC H10407) showed transepithelial electrical resistance (TEER) values higher in the ABB C1® group after 6 hours of testing. Spontaneous build-up of the gut epithelium monolayer over 22 days was also greater in the ABB C1® condition vs. a negative control. ABB C1® showed a significantly higher capacity to stimulate phagocytosis as compared with controls of algae β-1,3-glucan and yeast β-1,3/1,6 glucan (p &lt; 0.001). This study supports the mechanism of action by which ABB C1® may improve the immune response and be useful to prevent infection and allergy in clinical practice.

Food allergy (FA) affects approximately 6–8% of children worldwide causing a significant impact on the quality of life of children and their families. In the years, the possible role of weaning in the development of FA has been studied. According to recent studies, the role of weaning in its development is still controversial and influenced by several factors, such as the type of food, the age at food introduction and family history. In this narrative review, we aimed to collected the most recent evidence about weaning and its role in FA development, organizing the gathered data based on both the type of study and the food.

Extremely sensitive food-allergic patients may react to very small amounts of allergenic foods. Precautionary allergen labelling (PAL) warns from possible allergenic contaminations. We explored the ability of proteomic methods to identify minute amounts of milk/egg allergens in a brand of PAL-labelled milk- and egg-free biscuits. We evaluated the reactivity of children with severe milk and egg allergy, by oral food challenge. Traces of milk and/or egg allergens in biscuits were measured by two different liquid-chromatography-mass spectrometry methods. The binding of patient's serum with egg/milk proteins was assessed at immunoblotting. None of the patients reacted to biscuits. Egg and milk proteins were found under the limit of detection of 0.6 µg/g for milk and egg (method A), and of 0.1 and 0.3 µg /g for milk and egg, respectively (method B). The immunoblots did not show milk/egg proteins in the studied biscuits. Our biscuits did not contain allergens of clinical significance. Their milk/egg content is far lower than 4 µg of milk or egg protein per gram of product, the minimal doses considered theoretically capable of causing reactions. With high sensitivity, proteomic assessments predict the harmlessness of very small amount of allergenic foods and can be used to avoid unnecessary PAL.

Food allergies are a growing public health concern worldwide, especially in children and young adults. Allergen-specific IgE plays a central role in the pathogenesis of food allergies, but their titers poorly correlate with allergy development. Host immune systems yield allergen-specific immunoglobulin (Ig)A, IgE and IgG subclasses with low or high affinities and differential Fc N-glycosylation patterns that can affect the allergic reaction to food in multiple ways. High affinity IgE is required to induce strong mast cell activation eventually leading to allergic anaphylaxis while low affinity IgE can even inhibit the development of clinically relevant allergic symptoms. IgA and IgG antibodies can inhibit IgE-mediated mast cell activation through various mechanisms, thereby protecting IgE-positive individuals from allergy development. The production of IgE and IgG with differential allergenic potential seems to be affected by the signaling strength of individual B cell receptors, and by cytokines from T cells. This review provides an overview of the diversity of the B cell response and the diverse roles of antibodies in food allergy.

Same-day desensitization (SDD) is a procedure in which desensitization to the drug suspected of causing the hypersensitivity reaction (HR) is performed on the same day as the patient's reaction. In rapid drug desensitization (RDD), desensitization to the suspected drug is performed after an allergological study. The aim of the study was to analyze the diagnostic capacity of the allergist in Oncology Day Hospital (ODH) to establish the phenotype of the HR, in the context of SDD, based exclusively on clinical biomarkers. This is a study of patients treated with desensitization on the same day they had a HR. Later an allergological study (clinical history, skin test, risk assessment, serological biomarkers, drug provocation test if applicable) was performed prior to the following administrations. A total of 35 successful SDDs were performed. A high concordance (91.5% of patients) was found between the phenotype suspected by the allergist after the initial assessment of the patient prior to SDD and the final phenotype after subsequent allergological study performed in the Allergy Department. The presence of the allergist at the ODH allows, in addition to initial treatment according to phenotype, desensitization on the day of the reaction. This will lead to personalized and precision allergology.

Zn is an essential element for children related to optimal growth, development and nutritional metabolism. We measured Zn bioaccesibility (Zn-BA) levels of foods by Inductively coupled plasma mass spectrometry (ICP-MS) after in vitro digestion-fermentation method from children with gluten related disorders (GRD-CH), obesity (OB-CH) and allergy/intolerance to cow’s milk proteins (AICM-CH). Zn-BA levels in sick children (34.7 ± 28.8, 29.6 ± 30.1 and 26.7 ± 30.4%, respectively) were significantly lower (p &lt; 0.05) than in healthy norm-weight children (HE-CH). For AICM-CH, Zn-BA in animal foods was significantly lower than in plant foods, and in both plant and animal foods from sick and healthy children (p &lt; 0.05). In foods of animal origin in sick and healthy children, Zn-BA in foods heated in liquid media (frying and boiling) was significantly higher than in foods heated by hot air (roasting and grilling). In conclusion, in children the studied diseases diminished the Zn-BA, probably by the alteration of the gut microbiota which could negatively affect their appropriate long-term development. In AICM-CH, the allergy to cow's milk proteins could induce intestinal dysbiosis and inflammatory processes, leading to allergies to other animal food proteins, and to a more pronounced decrease of Zn-BA.

The prevalence of allergic diseases, including food allergy, is increasing, especially in developed countries. Implementation of an elimination diet is not a sufficient therapeutic strategy in patients with food allergy, whose quality of life is significantly impaired. In recent years, new effective therapeutic strategies have been developed, such as the application of oral, sublingual, and epicutenous immunotherapy. Oral immunotherapy is the most often applied strategy because of its effectiveness and ease of application, with an acceptable safety profile. The effectiveness of oral immunotherapy in patients with egg, cow's milk and peanut allergy has been proven both in terms of raising of the threshold and the development of tolerance, and in some patients, the development of sustainable unresponsiveness. Although oral immunotherapy is an effective treatment for food allergy, several limitations, including long duration and a significant rate of reported adverse events, reduces its success. Therefore, new therapeutic options, such as treatment with biologicals, either as combinations with food allergen immunotherapy or as monotherapy with the aim of improving the efficacy and safety of treatment are being investigated..

Elovanoids (ELV) are novel lipid mediators synthesized from very long-chain (VLC) omega-3 (n-3) polyunsaturated fatty acids (PUFA), particularly docosahexaenoic acid (DHA) or eicosa-pentaenoic acid (EPA), by the elongase enzyme ELOVL4. ELV have been shown to play a funda-mental role in maintaining brain and retina function, neuroprotection, maintaining the skin's permeability barrier, and sperm function, among other important cellular processes. Furthermore, the methyl ester or sodium salt of ELV-N32 and ELV-N34 have been found to be efficient in re-duced infarct volumes, promoting cell survival and decreasing the alteration of the neurovascular unit in a model of ischemia due to occlusion of the middle cerebral artery. Their bioactivity in-cludes enhancing of anti-apoptotic and pro-survival protein expression combined with the downregulation of pro-apoptotic proteins. House dust mite (HDM) is the most prevalent indoor allergen, and HDM exposure is frequently the cause of allergic respiratory disease, including aller-gic rhinitis and allergic asthma in HDM sensitized individuals. In our study, human nasal epithe-lial cells (HNEpC) were used as an in vitro model for allergy. The cells were challenged with HDM (mixture of Dermatophagoides farinae and D. pteronyssinus extract), with or without treat-ment with ELV-34. Phosphate-buffered saline (PBS) (vehicle) and ELV-34 (500 nM) alone were used as the control. Our findings show that ELV-34 promotes cell viability and reduces cytotoxi-city upon HDM sensitization of HNEpC. ELV-34 treatment significantly reduces the levels of IL-6, IL-1β, IL-8, VEGF, ICAM1, CXCL1 and CCL2, restored the IL-10 level and diminishes the induc-tion of the transcription of inflammatory and senescence genes in HNEpC. Our data also shows that HDM triggered the expression of several key genes in human nasal epithelial cells, including autophagy, unfolded protein response (UPR), Matrix metalloproteinases (MMPs), senescence and inflammation markers. Together, our data reveal a novel pro-homeostatic and cell-protective li-pid-signaling mechanism in nasal epithelial cells that envision novel potential therapeutic targets for the treatment of allergies.

Background: A decline in the prevalence of Helicobacter pylori infection has been claimed to increase the probability of developing atopic diseases. Aims: To evaluate the prevalence of atopic disorders in a pediatric population according to seropositivity against H. pylori. Methods: Children referred to the local Pediatric Hospital were investigated to identify risk factors, especially H. pylori infection, associated with atopic disorders. A questionnaire, including demographics, house size, history of breastfeeding, residence, school or daycare center attendance, exposure to animals, and a diagnosis of atopy, was filled out by a trained pediatrician according to parents’ answers. A blood sample was collected from each participant. Results: Seroprevalence of H. pylori infection was 11.7% among 492 children (240 females); 32 of them had a diagnosis of asthma and 12 of allergy. No one child showed both conditions. Statistically significant differences in H. pylori seropositivity were not detected between children with or without atopy (8.4 vs. 12.6; p=0.233). Although atopic disorders were more frequent in children exposed to traditional risk factors none showed to be significant after adjusting for all covariates. Conclusions: H. pylori infection, serologically assessed, was not significantly associated with a reduced risk of atopic diseases in children.

Elevated levels of immunoglobulin E (IgE) are associated with allergies and other immunological disorders. Experimentally, sensitization with alum adjuvant favors IgE production while CpG-ODN adjuvant, a synthetic toll-like receptor 9 (TLR9) agonist, inhibits it. The cellular mechanisms underlying TLR-regulation of immunoglobulin production are still controversial. Specifically, TLR-mediated IgE regulation in vivo is not yet known. We show that augmented levels of IgE induced by sensitizations to OVA with or without alum adjuvant or with OVA-pulsed dendritic cells (DCs) were inhibited when sensitization to OVA was performed in the presence of CpG. Notably, CpG-mediated suppression of IgE production required MyD88-expression on DCs but not on B-cells. This contrasts with previous reports of in vitro regulation IgE where CpG acted directly on B cells via MyD88 pathway. In addition, CpG also inhibited IgE production in a MyD88-dependent manner when sensitization was performed with OVA-pulsed DCs. Finally, CpG signaling through MyD88 pathway was also necessary and sufficient to prevent anaphylactic antibody production involved in active cutaneous anaphylaxis.

Background and Objectives: Peanut allergy is the most common single cause of anaphylaxis in children. The risk factors for anaphylaxis in children with peanut allergy are not well defined. Therefore, we aimed to identify epidemiological, clinical and laboratory characteristics of children with peanut allergy that may predict the severity of allergic reaction and anaphylaxis. Materials and Methods: We conducted a cross-sectional study and included 94 children with peanut allergy. Allergy testing was performed, including skin prick testing and determination of specific IgE levels to peanut and its Ara h2 component. In case of discordance between patient history and allergy testing, an oral food challenge with peanut was performed. Results: Anaphylaxis, moderate and mild reactions to peanuts occurred in 33 (35.1%), 30 (31.9%) and 31 (33.0%) patients, respectively. The severity of the allergic reaction only weakly correlated (p = 0.04) with the amount of peanuts consumed. The median number of allergic reactions to peanut was 2 in children with anaphylaxis compared with 1 in other patients (p = 0.04). The median level of specific IgE to Ara h2 was 5.3 IU/ml in children with anaphylaxis compared to 0.6 IU/ml and 10.3 IU/ml in children with mild and moderate peanut allergy (p = 0.06). The optimal cutoff for distinguishing between anaphylaxis and a less severe allergic reaction to peanut was a specific IgE Ara h2 level of 0.92 IU/ml with 90% sensitivity and 47.5% specificity for predicting anaphylaxis (p = 0.04). Conclusions: Epidemiological and clinical characteristics of the patient cannot predict the severity of allergic reaction to peanut in children. Even standard allergy testing, including component diagnostics, is a relatively poor predictor of the severity of allergic reaction to peanuts. Therefore, more accurate predictive models including new diagnostic tools are needed to reduce the need for oral food challenge in most patients.

Autism Spectrum Disorders (ASD) are neurodevelopmental disturbances affecting social skills, whose incidence worldwide is dramatically increasing. Together with the rise of ASD prevalence, several immune conditions are following the same trend, including Atopic Dermatitis (AD), with a possible clinical relationship with ASD. To date, their pathogenesis is still unknown, but several studies highlighted the relevance of gene-environment interactions to the onset of both disorders. Among potential contributing factors, microRNAs (miRNAs), small molecules capable of controlling gene expression and targeting mRNA transcripts, might represent one of the major circulating link, unraveling the connections between neurodevelopmental and immune conditions. We conducted a systematic literature review, under the PRISMA guidelines, trying to define the panel of common miRNAs involved in both ASD and AD. The review retrieved articles published until December 13, 2018, in PubMed, ScienceDirect, PsycARTICLES and Google Scholar. We found a handful works dealing with miRNAs in ASD and AD, with the most overlapping dysregulated miRNAs being miR-146 and miR-155. Two possible compounds are abnormally regulated in both ASD and AD subjects, possibly cross-contributing to the interactions between the two disorders, setting the basis to investigate more precisely the possible link between ASD and AD from another, not just clinical, perspective.

Bloody stools in the newborn may be a clue for several clinical entities of varying severity ranging from a transient hematochezia to food protein induced allergic proctocolitis (FPIAP) or necrotizing enterocolitis (NEC). To distinguish among them at an early stage is challenging, but crucial, as the treatment and prognosis are different. We conducted a monocentric retrospective study including all preterm infants admitted to the NICU of the Vittore Buzzi Children’s Hospital (Milan) with bloody stools from December 2022 to May. Patients diagnosed with NEC exhibited a significantly lower eosinophil count and higher procalcitonin levels than both patients with CMPA and patients with transient hematochezia, as well as a statistically significant increase in pathological features at abdomen ultrasounds and abdominal X-rays. In contrast, no Lab markers or imaging have been demonstrated to be useful in distinguishing between transient hematochezia and FPIAIP. Thus, after excluding a diagnosis of NEC the only way to confirm the FPIAP is the oral food challenge, which can be performed even in premature newborns presenting blood stools, otherwise healthy, under medical supervision, in order to identify infants who may benefit from a cow’s milk free diet.

Respiratory allergic diseases, affect over 500 million people globally and pose a substantial burden in terms of morbidity, mortality, and healthcare costs. Restrictive factors such as geographical disparities, infectious pandemics, limitations in resource, and shortage of allergy specialists in underserved areas, impede effective management. Moreover, the well-established suboptimal adherence in patients with respiratory allergies, contribute further to the accelerated loss of disease control. Telemedicine encompasses real-time visits, store-and-forward options triage, and computer-based technologies for establishing and efficient doctor-patient communication. Recent advances in digital technology, including designated applications, informative materials, digital examination devices, wearables, digital inhalers, and integrated platforms, facilitate personalized and evidence-based care delivery. The integration of telemonitoring in respiratory allergy care has shown beneficial effects in disease control, adherence, and quality of life. While the COVID-19 pandemic accelerated the adoption of telemedicine, certain concerns regarding technical requirements, platform quality, safety, reimbursement, and regulatory considerations remain unresolved. Challenges in telemonitoring implementation further include ensuring effective doctor-patient collaboration, addressing privacy concerns, and establishing cost-effective models. The integration of artificial intelligence (AI) in telemonitoring applications holds promise for data analysis, pattern recognition, and personalized treatment plans. Striking the balance between AI-enabled insights and human expertise is crucial for optimizing the benefits of telemonitoring. This overview reports the up- to- date telemedicine approaches in managing patients with respiratory allergies. While telemonitoring exhibits potential in enhancing patient care and healthcare delivery, critical considerations have to be addressed in order to ensure the successful integration of telemonitoring into the healthcare landscape.

Immunology is a branch of medicine that studies the immune system and its pathology. There are known scientific informations, that in medical immunology specific tests performed in the laboratory for diagnosis. In addition good to mention that allergies include medical diagnostic methods such as blood tests. Also there are used for detection the presence and the levels of IgE antibodies. These antibodies are produced by the human immune system in contact with certain allergens. Examples of allergens include for example pollen, house dust, some herbs or molds, some animals and certain foods. If a person has an allergy, their immune system overreacts to an allergen by producing antibodies, called Immunoglobulin E (IgE). Currently within the present describtion aim to discuss some aspects reffering to fungal allergen and mold allergy diagnosis, in a briefly following steps of our purposed shortly review.

In contrast to Th1 immune responses against pathogenic viruses and bacteria, the incipient events that generate Th2 responses remain less understood. Part of the difficulty in identifying universal operating principles stems from the diversity of entities against which cellular and molecular Th2 responses are produced. Indeed, such responses are launched towards harmful macroscopic parasites and noxious substances such as venoms but also against largely innocuous allergens. This suggests that the canonical understanding about sensing and recognition applied to Th1 responses may not be translatable to Th2 responses. This review will discuss processes and signals known to occur in Th2 responses, particularly in the context of food allergy. We propose that perturbations of homeostasis at barrier sites induced by external or internal subverters that either activate the immune system or lower its threshold activation are the major requirement for allergic sensitization. Innate signals produced in the tissue under these conditions equip dendritic cells with a program that shapes an adaptive Th2 response.

Hymenoptera allergens are the main triggers for anaphylaxis in susceptible dogs and humans. Hymenoptera venom specific immunotherapy (VIT), the only disease-modifying treatment, has the potential to prevent future life-threatening reactions in human patients. Prospective clinical data on VIT efficacy in dogs are currently lacking. Therefore, the aim of this study was to show that VIT is not only safe but also efficacious in preventing anaphylaxis in dogs allergic to Hymenoptera. This uncontrolled prospective clinical trial included 10 client-owned dogs with a history of anaphylaxis following repeated Hymenoptera stings. The sensitization to bee and wasp allergens was demonstrated by intradermal testing (IDT) and allergen-specific IgE serology. For VIT induction (induction phase), dogs received a shortened rush immunotherapy protocol with aqueous allergens, which was then followed by monthly injections of 100 g of alum-precipitated allergen (maintenance phase). VIT efficacy was determined by observing patients’ clinical reactions to re-stings. No systemic adverse events were seen during the induction and maintenance phase. From the seven re-stung dogs, only one developed a mild angioedema at the site of the sting; the remaining dogs were asymptomatic. These results show that VIT represents a safe and effective treatment option for Hymenoptera-allergic dogs.

Mosquitoes are a family of the order Diptera, which includes more than 3500 species. Two groups able to suck human blood and transmit diseases: the anophelines and the culicines comprise several genera such as Culex, Aedes and Aedes communis (Ac). Previous study has demonstrated a significant relationship between Ac sensitization and either extract or single bee venom components suggesting a “bee-mosquito syndrome” occurrence. It is well known that CCD can interference with the measurement of quantitative IgE results. Hence, it has been hypnotized that the presence of sIgE to CCD could have a role in the Bee-Mosquito syndrome. Method Serum from 21 different Mosquito and Ape melifera allergic individuals were combined with extracts of Mosquito (in house) and Apis melifera. SDS-PAGE and Immunoblot (IB) were carried out without and with with CCD-Inhibitor. Results The data would suggest IgE binding to common bands between Culex male, Culex female and Aedes species mosquitos of approximate molecular weight ~21kDa, ~35kDa, ~40kDa and ~55kDa. Whilst IgE binding has been observed to protein bands from the Apis melifera extract, these bands do not align with any present in the mosquito extracts. The use of a CCD-Inhibitor results in differences in IgE binding. Specifically, bands that were previously observed in the Apis melifera venom sample without use of CCD-Inhibitor at 40kDa and 90kDa are no longer observed when CCD-Inhibitor is used. Two bands of the Apis melifera venom remain present between 15-20kDa. No major differences in banding pattern were observed for the mosquito samples with or without CCD-Inhibitor, although the blot appears cleaner with less background when CCD-Inhibitor is used. Conclusion Further experiments have to be done to determine whether the reactive bands from Apis melifera are unrelated proteins or whether the proteins are related homologues of varying molecular weight.

High prevalence of allergic disorders in Indian pediatric patients demands early diagnosis of allergens so that appropriate allergen avoidance methods, pharmacotherapy or immunotherapy can be provided in time to avoid the worsening of symptoms due to triggers. In this context, identification of the most prevalent aeroallergens in a given area is critical for diagnosis and treatment of various allergic reactions especially in case of rhino-conjunctivitis and asthma. The specific diagnosis of IgE mediated allergy is usually based on the correlation between the clinical history and signs and symptoms endorsed by the diagnostic tests. Skin prick tests are the gold standard however has some limitation. In view of this, the aim of this study was to assess the significance of ImmunoCAP assay for assessing serum specific IgE levels, available in India, against skin prick test by standardized allergens, for the diagnosis of allergic sensitization. A single-center observational study was conducted at tertiary care corporate hospitals in North India from 2017-2020. Patients with self-reported allergic symptoms or whose symptoms were suspected for allergies were tested for the type of sensitization using skin prick test (SPT) after their consents followed by ImmunoCAP based quantification of serum specific IgE levels. A total of 256 (95.9%) pediatric patients were analyzed in the study and were analysed. The patients were most commonly (30% patients) sensitized to D. farinae (173 [67.6%]), D. pteronyssinus (174 [68.0%]), Acarus siro (93 [36.3%]), Lepidoglyphus destructor (96 [37.5%]), Plantago lanceolata (Engl.). The ROC curve of Bermuda grass shows that the AUC of serum-specific IgE is larger than that of SPT (1.000 / 0.881). The receiver operating characteristic (ROC) analysis of serum-specific IgE reference method resulted in the largest AUC of all the allergens taken into consideration (0.711 / 1.000) compared to those of SPT (0.589 / 1.000). These results revealed that serum-specific IgE is more reliable method over prick test for accessing the sensitivity of patient for various allergens. This study may be helpful in performing early diagnosis of allergies as well as in taking appropriate preventive measures for managing life threatening allergic reactions

Food allergy has been recognised by the World Health Organisation as a chronic disease that could lead to fatality. The symptoms can mediate from mild to severe consequences. Some cases have reported that food allergy sufferers are bullied and are discriminated at workplace, thus increasing their stress level, apart from facing difficulty in consuming certain food due to allergy. This has an adverse effect on the quality of life amongst food allergy sufferers. Medical bills are increased when food allergy sufferers become unknowingly exposed to food allergen. Hence, this study investigated food allergens among food allergy sufferers in order to make their lives better. A total of 250 respondents participated in an online survey. Surprisingly, apart from chicken, soybean and other food allergens that have been listed under the Big Eight Allergens, the respondents mentioned some fruits that could trigger allergic reactions, such as rambutans and watermelons. Food allergy sufferers can be allergic to seafood and seafood products as well, such as shrimp paste or locally known as belacan, which refers to fermented shrimp paste cured under the sun. It is a common food ingredient used among Malaysians. The study findings offer practical insights, such as avoidance of food allergens amidst food allergy sufferers and help the government to carefully manage for menu planning. The knowledge contribution of this study reveals several specific food and fruits, as aforementioned, which appear to be common and nutritious food, yet harmful to food allergy sufferers.

The aim of this research was to select apple varieties suitable for allergy sufferers and diabetics. We first conducted a comprehensive analysis of several apple varieties. The total polyphenol content, sugar content, acidity, and antioxidant activity of the apple fruit juices were determined using spectrophotometric techniques. We also measured the amounts of polyphenols in the apple skins and their antioxidant potential, as well as the allergenic content in the apple juices. The strength of sensitization was assessed using the ELISA method. The lowest amounts of Bet v 1 homologues were found in the varieties Kosztela (4.21 ± 0.71 µg/g), Koksa Pomarańczowa (4.24 ± 0.08 µg/g), and Reneta z Brownlee (4.86 ± 0.18 µg/g). Low values for profilin were observed for Renet Harbert (1.74 ± 0.22 ng/g) and Schieblers Taubenapfel (2.26 ± 0.12 ng/g). The highest values for profilins and Bet v 1 homologues were found in the Złotka Kwidzyńska variety (12.40 µg/g), followed by Malinowa Oberlandzka (9.86 µg/g) and Jakub Lebel (8.87 µg/g). The varieties richest in profilin were Reneta Blenheimska (8.81 ng/g), Szara Reneta (7.88 ng/g), Pepina Ribston (7.67 ng/g), and Reneta z Brownlee (7 .63 ng/g). Given their minimal content of both profilins and Bet v 1 homologues, Koksa Pomarańczowa (4.24 ± 0.08 µg/g Bet v 1 and 4.49 ± 0.82 ng/g profilins) and Książę Albrecht Pruski (5.57 µg/g Bet v 1 and 3.34 ng/g profilins) were identified as suitable for people with allergies. For diabetics, the most suitable apple variety was found to be Jakub Lebel, providing large doses of antioxidants and polyphenols (41.1 ± 2.0 and 5.16 ± 0.42, respectively) and a relatively low sugar content (9.06). Similar results were measured for Kingfish, with 10.2 sugars, 5.68 ± 0.49 antioxi-dants, and 46.2 ± 1.5 polyphenols. The Galowany Pipping variety was found to have a low sugar content (9.71), corresponding to a perceived sweetness of 2.5. Prince Albert of Prussia apples had high antioxidant potential (5.70 ± 0.77) and a low sugar content (11.09). The James Grieve apple variety provided a high polyphenol content of 63.3 ± 1.1 with a high antioxidant level of 5.34 ± 0.45. Grochówka offers a combination of a high polyphenol content (48.6 ± 1.9), a high level of antiox-idant protection (5.50 ± 0.34), and a very low perceived sweetness (from 3.0).

Background: Gingival enlargement is defined as an abnormal overgrowth of gingival tissues. A case of a 34–year–old female presenting with maxillary chronic inflammatory gingival enlargement associated with a nickel wire allergy is reported here. Replacement of the wire, good oral hygiene therapy and surgical therapy was carried out to provide a good aesthetic outcome. Histopathological evaluation was done of the excised specimen. There is only one similar case reported in literature to the best of our knowledge and ours is the second case. Result: A Histopathological diagnosis of inflammatory fibrous hyperplasia was established. No recurrence was reported at the end of 1 year. Conclusion: The patient should be made aware of the allergy at the initial visit and oral hygiene instructions should be reinforced at every visit. The significance of patient compliance during and following therapy as an important factor in the success of treatment.

Background: Data suggest that food allergies greatly impact a child’s health and growth due to inadequate nutrient intake. Our study aimed to establish the long-term outcome of children with food allergies compared to a control group. Methods: This study was a retrospective cohort study with longitudinal follow-up with a mean period of 4.85 years from the diagnosis to the last study visit. The patients’ nutritional intake was assessed using a three-day food diary and analysed by a dietitian. Patients (61 boys and 33 girls, mean age 6.9 years) had a single food allergy including 21 patients with cow’s milk, 34 with egg, and 39 with peanut allergies. The control group included 36 children (19 boys and 17 girls, mean age 8.03 years). Blood analysis was performed on all participants. Results: Data from our study showed that patients with cow’s milk, egg or peanut allergies had normal growth and achieved catch-up growth from the diagnosis until the last study visit. In the cow's milk allergy group, the allergy was shown to affect calcium intake (p&lt;0.05), while egg and peanut allergies did not impact the dietary intake of nutrients. None of the investigated food allergies affected blood results (p&lt;0.05). Conclusions: In the present study, we showed that single food allergies do not compromise growth in children if they are provided with appropriate support and that the affected children reach catch-up growth from the diagnosis.

Introduction: The rising trend in allergic diseases has occurred in parallel with an increasing prevalence in obesity, and suggesting a possible association. The increased body mass has numerous health consequences, including an impairment function of the respiratory system. The associations between eating habits and hypersensitivity to allergens have not been clarified sufficiently. Aim: to evaluate pulmonary function, nutritional status, eating habits and risk factors of obesity in children and adolescents with allergic rhinitis. Material and Methods: The study was performed in 106 children with allergic rhinitis (mean age 12.1+/-3.4; M/F 60/46) from the Department of Allergology. 43 (40.6%) of children presented only allergic rhinitis and in 63 (59.4%) additionally diagnosed with asthma bronchiale. Clinical data, detailed interview about allergies, assessment of pulmonary function and nutritional status, allergy skin test (Allergopharma) and spirometry (Jaeger) were evaluated. Nutritional habits were assessed by a food frequency questionnaire. The statistical analysis was done using the program Statistica v 10.0. Results: In the study group the mean centile of BMI was 49.4; underweight presented 25.4% of children, 55.6 % normal BMI and 18.8 % presented overweight or obesity. Multiple regression analysis showed a significant (adjusted R-squared: 0.97; p<0.05) association between high BMI and snacking between meals and low physical activity. No statistical association between the severity of diseases and BMI or body composition was observed. Conclusions: 1. The prevalence of excess body mass in the study group reached 13.5%. Eating habits were incorrect, especially obese children significantly more frequently ate snacks between meals than children with normal body weight. 2. Among the studied group of children and adolescents with allergic rhinitis and asthma bronchiale, the significant risk factors of obesity were snacking and low physical activity.

Recent evidence has highlighted the critical role of memory cells in maintaining lifelong food allergies, thereby identifying these cells as therapeutic targets. IgG⁺ memory B cells replenish pools of IgE-secreting cells upon allergen exposure, which contract thereafter due to the short lifespan of tightly regulated IgE-expressing cells. Advances in the detection and highly dimensional analysis of allergen-specific B and T cells from allergic patients have provided insight on their phenotype and function. The newly identified Th2A and Tfh13 populations represent a leap in our understanding of allergen-specific T cell phenotypes, though how these populations contribute to IgE memory responses remains poorly understood. Within, we discuss the mechanisms by which memory B and T cells are activated, integrating knowledge from human systems and fundamental research. We then focus on memory reactivation; specifically, on the pathways of secondary IgE responses. Throughout, we identify areas of future research which will help identify immunotargets for a transformative therapy for food allergy.

Microorganisms have colonized all barrier tissues and are present on the skin and all mucous membranes since birth. Bacteria have many ways of influencing the host organism: activation of innate immunity receptors by PAMPs; synthesis of various chemical compounds, such as vitamins, short-chain fatty acids, bacteriocins, toxins. Bacteria, using extracellular vesicles, can introduce high-molecular compounds, such as proteins and nucleic acids, into the cell, regulating the metabolic pathways of the host cells. Epithelial cells and immune cells recognize bacterial bioregulators and, depending on the microenvironment and context, determine the direction and intensity of the immune response. A large number of factors influence the maintenance of symbiotic microflora, the diversity of which protects host against pathogen colonization. Reduced bacterial diversity is associated with pathogen dominance and allergic diseases of the skin, gastrointestinal tract, upper and lower respiratory tract, as seen in atopic dermatitis, allergic rhinitis, chronic rhinosinusitis, food allergies, and asthma. Understanding the multifactorial influence of microflora on maintaining health and disease determines the effectiveness of therapy and disease prevention, changes our food preferences and lifestyle to maintain health and active longevity.

Although wheat is a staple food for most of human population, some of its components trigger adverse reactions. Among wheat components, the alpha-amylase/trypsin inhibitors (ATI) are important triggers of several allergies and activators of innate immunity. ATI are a group of exogenous protease inhibitors and include several polypeptides. The three ATI polypeptides named CM3, CM16 and 0.28 are considered major allergens, and might also play a role in other common wheat-related pathologies, such as Non Celiac Wheat Sensitivity and even Celiac Disease. On this basis, we pointed to obtain high amounts of them in purity and evaluating their allergenicity potential. We thus isolated the mRNA corresponding to the three ATI genes CM3, CM16 and 0.28 from 28 days post-anthesis wheat kernels and the corresponding cDNAs were used for heterologous expression in Pichia pastoris. The three purified proteins were tested in degranulation assay against human sera of patients with food allergy to wheat. A large range of degranulation values was observed for each protein according to the sera tested. All the three purified proteins CM3, CM16 and 0.28 were active as allergens because able to induce basophils degranulation on wheat allergic patients’ sera, but the highest values of β-hexosaminidase release were observed for CM3 protein.

Inhalation allergies caused by cats and dogs can lead to a range of discomforting symptoms, such as rhinitis and asthma, in humans. Given the increasing popularity and care provided to these companion animals, the allergens they produce pose a growing threat to the health of susceptible patients. Allergens from cats and dogs have emerged as significant risk factors for triggering asthma and allergic rhinitis worldwide; however, there remains a lack of systematic measures aimed at assisting individuals in recognizing and preventing allergies caused by these animals. This review provides comprhensive insights into the classification of cat and dog allerges, alongwith their pathogenic mechanisms. The study also discusses implementation strategies for prevention and control measures, including physical methods, gene editing technology, immunological approaches, as well as potential strategies for enhancing allergen immunotherapy combined with immunoinformatics. Finally, it presents future prospects for the prevention and treatment of human allergies caused by cats and dogs. This review will improve knowledge regarding allergies to cats and dogs, while identifying potential targets for the development of next-generation treatments.

Previous studies have shown that immunization within the first hours/days after birth promotes the shift from the intrauterine Th2 immune response toward the Th1 immunity resulting in lower risk of developing allergic diseases. We are currently conducting a prospective cohort study among 307 participants divided into groups based on their TB and hepatitis B vaccination status (vaccinated at birth, within the first 12 months of life or unvaccinated) and also based on whether the participants had factors contributing to the development of allergic diseases. In each group we assessed the fact of primary diagnosis of atopic dermatitis at 12 and 18 months of age. It was demonstrated that atopic dermatitis (AD) was diagnosed from birth to 12 months of age much less frequently in those infants who had received the tuberculosis (TB) vaccine from day 3 to day 7 and hepatitis B vaccine within the first 24 hours of birth, including newborns with a high risk of developing allergic diseases. The probability of onset of AD at 12 and 18 months was also lower in timely vaccinated children, even though a burdened allergic anamnesis starts playing a more central role in development of AD at this age. Our findings testify to the fact that timely BCG-M and hepatitis B vaccination can produce a protective effect against the onset of AD, yet this effect diminishes with aging.

Hymenoptera, which includes honeybees, wasps, bumblebees, and hornets, is an order of the class Insecta whose venom can induce anaphylactic reactions in dogs. While several studies have investigated the natural histories and risk factors of Hymenoptera venom allergy (HVA) in humans, only limited information is available on canine patients. Therefore, the aim of this study was to identify risk factors leading to severe systemic reactions (SSR) and to explore the natural history of these patients. This was achieved with an inquiry into the case histories of 178 dogs that were stung by Hymenoptera between 2018 and 2022. Dogs under two years old, dogs that weighed under 10kg, purebred dogs and dogs that were stung in the oral cavity were at a greater risk of developing SSR. Almost two thirds of patients with SSR experienced the same or worse symptoms after subsequent stings and &gt; 40% of patients with local reactions developed SSR when stung again. Next to providing valuable clinical information of HVA in dogs, these findings strongly support the recommendation of venom immunotherapy (VIT) for patients with HVA.

Fungi kingdom comprises ubiquitous forms of life with 1.5 billion years, mostly phytopathogenic and commensal for humans and animals. However, in the presence of impaired conditions fungi may cause disease by intoxicating, infecting or sensitizing with allergy. Different genera may be implicated as etiological agents for humans and animals, with Alternaria, Aspergillus, dermatophytes like Microsporum and Trichophyton, and Malassezia as the commonly implicated. Alternaria and Malassezia stand as the most commonly associated to either allergy or infection, immediately followed by Aspergillus, while dermatophytes are usually associated to ring worm skin infection. Research in veterinary field is not much but necessary.

Adopting an immune response and tissue-based nomenclature in food allergies brings the field closer to precision and personalized medicine. An updated classification of non-IgE-mediated food hypersensitivity highlights mechanisms through a complex pathophysiological perspective and endotype-driven framework. This approach aligns with the essential goals of discovering new diagnostic and therapeutic biomarkers, enhancing the understanding of clinical presentations, and refining immunotherapy and targeted treatments, such as monoclonal antibodies and small molecule drugs, to improve patient management and quality of life. Endotype-focused and molecular-based decision-making also endows translational and clinical research, fostering the ongoing scientific quest for more innovative solutions.

The prevalence of food allergy has increased in recent years, especially in children. Food allergen avoidance and symptomatic drugs in case of an allergic reaction remain the standard of care in food allergy. Nevertheless, increasing attention has been given to the possibility to treat food allergy, through immunotherapy, particularly oral immunotherapy (OIT). Several OIT protocols and clinical trials have been published. Most of them focus on children allergic to milk, egg, or peanuts, although recent studies developed protocols for other foods, such as wheat and different nuts. OIT efficacy in randomized controlled trials is usually evaluated as the possibility for patients to achieve desensitization, while the issue of a possible long-term sustained unresponsiveness has not been completely addressed. Here, we evaluated current OIT knowledge, focusing on the results of clinical trials and current guidelines. Specifically, we wanted to highlight what is known in terms of OIT efficacy and effectiveness, safety, and impact on quality of life. For each aspect, we reported the pros and the cons, inferable from published literature. In conclusion, even though many protocols, reviews and meta-analysis have been published on this topic, OIT remains a controversial therapy and no definitive generalized conclusion may be drawn so far. It should be an option provided by specialized teams, when both patients and their families are prone to adhere to the proposed protocol. Efficacy, long-term effectiveness, possible role of adjuvant therapies, risk of severe reactions including anaphylaxis or eosinophilic esophagitis, and impact on the quality of life of both children and caregivers are all aspects that should be discussed before starting OIT. Future studies are needed to provide firm clinical and scientific evidence, which should also consider patient reported outcomes.

Aims: To compare the growth, safety, and tolerance acquisition in infants with cow's milk protein allergy (CMPA) when fed a hydrolyzed rice formula (HRF) versus an extensively hydrolyzed milk protein formula (EHF). Methods: A prospective, multicenter, randomized, double-blind, controlled trial was conducted with infants diagnosed with CMPA, both IgE-mediated and non-IgE-mediated (up to grade II anaphylaxis). Infants were assigned to receive either a HRF or an EHF over a 12-month follow-up period. The primary outcomes assessed were anthropometric measurements and safety. Infants who had a negative Open Oral Food Challenge (at 6, 9, and 12 months) were allowed to transition to a standard milk formula. Compliance, tolerability, and adverse events (AEs) were also evaluated. Results: A total of 105 children from six centers were enrolled in the study. Measurements of weight, length, weight-for-length, BMI, and head circumference z-scores indicated normal growth, with no significant differences between the HRF and EHF groups at baseline or during follow-up visits. Additionally, triceps skinfold thickness, mid-arm circumference, and arm muscle area showed no significant differences between the groups. Overall, 29 product-related adverse events were reported (12 in the HRF group and 17 in the EHF group). Five children in the HRF group and eleven in the EHF group experienced serious adverse events; none were attributed to the intervention. There was a trend toward faster acquisition of tolerance in HRF-fed infants compared to EHF-fed infants, but this did not reach statistical significance (median age 20.4 months versus 16.3 months, respectively, p=0.1753). Conclusions: Both EHF and HRF demonstrated appropriate growth, acquisition of tolerance, and a good safety profile in infants with CMPA, with no significant differences between the formulas.

Food allergies have increased significantly in recent decades, with shellfish being a leading cause of food allergy and anaphylaxis worldwide, affecting both children and adults. The prevalence of shellfish allergies is estimated to be approximately 0.5-2.5% of the general population, varying significantly by geographical location, age, and consumption habits. Although mollusk consumption has risen, the prevalence of mollusk allergies remains unknown. While extensive research has focused on crustacean allergies, mollusk allergies, particularly those related to gastropods, have received comparatively less attention. Clinical manifestations of shellfish allergy range from localized symptoms to life-threatening systemic reactions, such as anaphylaxis. Notably, severe bronchospasm is a predominant clinical feature in cases involving gastropods. Several allergens have been identified in mollusks, including paramyosin, tropomyosin, and sarcoplasmic calcium-binding protein. In gastropods, documented allergens include tropomyosin, paramyosin, the heavy chain of myosin, and Der p 4 amylase. Diagnosis typically involves a thorough clinical history, skin testing, in vitro quantification of immunoglobulin (Ig) E, and confirmation through oral challenge, although the latter is reserved for selected cases. This review highlights the limited research on gastropod allergy, the identified allergens to date, and the necessity for further investigations to better understand the implications of shellfish allergy within this class.

Wheat, a component of the staple diet globally, is a common food allergen in children. The symptoms of wheat allergy (WA) range from skin rash to shortness of breath, significantly impairing quality of life. Following initial clinical suspicion, individuals may undergo wheat allergen-specific skin prick test (SPT), blood test for serum immunoglobulin E (sIgE) levels or oral food challenge. Conventional management of WA lies in wheat avoidance, yet accidental consumption may be inevitable owing to the ubiquity of wheat in various food products. This article aims to provide an overview of the immunologic pathway of WA, followed by its novel diagnostic methods, namely alcohol-soluble SPT extracts, component-resolved diagnosis and basophil activation test (BAT). The mechanisms underlying wheat allergen-specific oral immunotherapy (OIT) as well as a summary of the efficacy, tolerability and safety of related clinical trials will then be discussed.

Canine atopic dermatitis (CAD) is a common chronic allergic skin disease. In our previous study, we isolated two probiotic strains, Lactococcus cremoris subsp. cremoris MP01 and Lacticaseibacillus paracasei subsp. paracasei MP02, from Mongolian fermented milk. These strains demonstrated potential in alleviating symptoms similar to AD and reducing specific immunoglobulin E (IgE) levels in a mouse model of AD. Building upon this discovery, our current investigation sought to evaluate the therapeutic potential of these probiotics for treating CAD. We conducted an open-label, single-arm clinical trial where dogs diagnosed with AD were administered LCP capsules containing Lc. cremoris subsp. cremoris MP01 and L. paracasei subsp. paracasei MP02 once daily for 60 days. Stool, skin swab, and venous blood specimens were collected at three intervals: before, and after 30 and 60 days of LCP intervention. The skin and fecal microbiomes were analyzed using full-length 16S rRNA sequencing. After 60 days of LCP intervention, notable improvements were observed in skin lesions and scratching behaviors, accompanied by reductions in both the Canine Atopic Dermatitis Extent and Severity Index (CADESI) and the Pruritus Visual Analogue Scale (PVAS) scores. Additionally, LCP intervention resulted in significant reductions in IgE levels and modulation in type 1 T helper (Th1)/ type 2 T helper cells (Th2)-related cytokine secretion. Microbiota analysis unveiled changes in the composition of both skin and gut microbiotas, including reductions in Shigella flexneri on the skin and Romboutsia in the gut. Levels of short-chain fatty acid (SCFA) increased following the 60-days of LCP intervention. These effects were likely mediated by alterations in gut microbiota and the upregulation of SCFA levels, which subsequently reduced the secretion of allergy-related IgE. Collectively, these mechanisms contributed to alleviating CAD symptoms, regulating skin microbiota composition, and reducing the adherence and invasion of environmental microbes and pathogens. Overall, our findings highlight the promising therapeutic potential of the Lc. cremoris subsp. cremoris MP01 and L. paracasei subsp. paracasei MP02 mixture as an effective strategy for managing CAD in dogs.

Mucosal vaccines can target specific mucosal surfaces, such as the respiratory, genital, or intestinal mucosa. Conventional systemic immunization, such as intramuscular injections, do not provide mucosal immunity, including IgA, nor do they prevent pathogens from entering the mucous membranes. Nasal immunization protects mucosal membranes, but nasal antigen presentation appears to entail adjuvant to stimulate immunogenicity. Current treatments for mucosal diseases such as inflammatory bowel disease (IBD) and allergic dermatitis only aimed to temporarily relieve symptoms. Moreover, these treatments not only have drug resistance or side effects, but the disease can recur, leading to switching to other treatments. Therefore, there is a need to develop safe and effective treatments that provide better long-term outcomes to reduce the risk of recurrence. Regulatory T (Treg) cells have been used to suppress inflammation. To find advances in mucosal treatment, we investigated the therapeutic effects of intranasal pep27 mutant immunization. Here, a new method of Treg induction through intranasal immunization without adjuvant has been developed to potentially overcome allergies and mucosal inflammation of the lung-gut axis in animal models. The implementation of the pep27 mutant for these therapies should be preceded by studies of Treg resilience through clinical translational studies of dietary changes.

Thanks to its valuable assessment possibilities (subjective complaints and changes in nasal patency in the course of the examination), nasal provocation test may serve as an alternative tool for oral food challenges in the future. However, this test requires successive attempts to regulate its methodology in order to develop a standardized lyophilisate form and determine the threshold dose for a positive result. The study objective was to present the methodological foundation for nasal food allergen provocation tests induced by freeze-dried powdered chicken egg white. A control group of 25 individuals with no history of allergy to chicken eggs or any other allergy was included in the study. Optical rhinometry and visual analog scale were used to assess the response of nasal mucosa to local allergen challenge. Minor variations in nasal flows as measured by optical rhinometry were observed in the provocation tests. The mean optical density measurements (as measured regardless of the allergen dose used) varied from positive to negative values and vice versa; e.g., amounting to 0.018 OD (standard deviation 0,095) at 15 minutes and −0.011 OD (standard deviation 0,090) at 30 minutes. No significant differences were observed with regard to the perceived nasal discomfort using the visual analog scale. Due to the absence of nasal mucosal reactivity, nasal challenge is an excellent methodological tool for implementing food allergen tests.

Asthma is a heterogeneous and very complex group of diseases, which includes different clinical phenotypes depending on symptoms, progression, exacerbation pattern or response to treatment among other characteristics. The allergic phenotype is the most frequent, especially in pediatric asthma. It is characterized by sensitization (production of specific IgE) to allergens, and frequent comorbidity with rhinitis and atopic dermatitis. An allergen is a substance that triggers the production of specific IgE antibodies in susceptible individuals, who present symptoms that will depend on the type and intensity of the allergenic load and the tissue where the interaction occurs. Airborne allergens cause their effects in the respiratory tract and eyes, and can be indoor or outdoor, perennial or seasonal. Although allergens such as mites, pollens or animal dander are generally considered as a single particle, it is important to note that they contain different molecules which could trigger distinct specific IgE molecules on different patients.The key points that a physician who treats asthma should be aware of are:

The incidence and prevalence of food allergy (FA) are increasing. While several studies have established the safety and efficacy of early introduction of single allergens in infants for the prevention of FA, the exact dose, frequency, and number of allergens that can be safely introduced to infants particularly in those at high or low risk of atopy are still unclear. This 1-year study evaluated the safety of early introduction of single foods (milk, egg, or peanut), vs. two foods (milk/egg, egg/peanut, milk/peanut), vs. multiple foods (milk/egg/peanut/cashew/almond/shrimp/walnut/wheat/fish/soy at low, medium, or high doses) vs no early introduction in infants between 4-6 months of age. At the end of the study, they were evaluated for plasma biomarkers associated with food reactivity with standardized blood tests. Two to four years after the start of the study, participants were evaluated by standardized food challenges. The serving sizes for the single, double, and low dose mixtures were 300 mg total protein per day. The serving sizes for the medium and high dose mixture was 900 mg and 3000 mg total protein, respectively. Equal parts of each protein were used for double or mixture foods. All infants were breastfed until at least 6 months of age. Results demonstrate that infants at either high or low risk for atopy were able to tolerate early introduction of multiple allergenic foods with no increases in any safety issues, including eczema, FA, or food protein induced enterocolitis. The mixtures of foods at either low, medium, or high doses demonstrated trends for improvement in food challenge reactivity and plasma biomarkers compared to single and double food introductions. The results of this study suggest that early introduction of foods, particularly simultaneous mixtures of many allergenic foods is efficacious for preventing FA and can occur safely.

Background: Little is known about the natural history of immunoglobulin (Ig) E-mediated diseases in preterm infants, further hampered by the lack of noninvasive investigations. We aimed at developing a non-invasive tool for the study of IgE and eosinophil-derived neurotoxin (EDN) in neonatal fecal samples and evaluating its predictive value for the development of IgE-mediated diseases (cow’s milk allergy, asthma, or atopic dermatitis) during the first year of life. Methods: We developed a stool extraction protocol, followed by freeze-drying and solubilization. sIgE responses were investigated in neonatal fecal samples from 21 preterm infants with a 300-allergen multiplex containing whole and molecular allergens and confirmed by capillary Western blot with nano-immunoassay. The local eosinophilic component was investigated by measuring the concentration of EDN. Results: The multiplexed allergen assay detected sIgE in all samples. Confirmation was obtained with Western blot. Frequency and levels of sIgE in neonatal fecal samples differed between infants who developed IgE-mediated diseases and controls. Neonatal fecal sIgE directed to milk proteins predicted later development of cow’s milk allergy (specificity 88%, sensitivity 78%). Allergen specificity of neonatal fecal sIgE was associated with later development of cow’s milk allergy and asthma. Neonatal fecal EDN levels predicted the development of IgE-mediated diseases (sensitivity 100%, specificity 75%). Conclusion: Non-invasive investigation of neonatal fecal sIgE is a promising tool for the prediction of subsequent development of IgE-mediated diseases.

Although wheat is used worldwide as a staple food, it can give rise to adverse reactions, for which the triggering factors have not been identified yet. These reactions can be caused mainly by kernel proteins, both gluten and non-gluten proteins. Among these latter, -amylase/trypsin inhibitors (ATI) are involved in baker’s asthma and realistically in Non Celiac Wheat Sensitivity (NCWS). In this paper, we report characterization of three transgenic lines obtained from the bread wheat cultivar Bobwhite silenced by RNAi in three ATI genes CM3, CM16 and 0.28. We have obtained transgenic lines showing an effective decrease of the activity of target genes that, although showing a higher trypsin inhibition as a pleiotropic effect, generate a lower reaction when tested with sera of patients allergic to wheat, accounting for the important role of the three target proteins in wheat allergies. Finally, these lines show unintended changes differences in high molecular weight glutenin subunits (HMW-GS) accumulation, involved in technological performances, but do not show differences in terms of yield. The development of new genotypes accumulating a lower amount of proteins potentially or effectively involved in such pathologies, not only offers the possibility to use them as a basis for the production of varieties with a lower impact on adverse reaction, but also to test if these proteins are actually implicated in those pathologies for which the triggering factor has not been established yet.

Wasp venom allergy can trigger severe allergic reactions, and predicting these acute responses remains challenging. This study evaluates the utility of immune system indexes, particularly the eosinophil-basophil/lymphocyte (EBLR) and eosinophil-basophil-platelet/lymphocyte (EBP/L) ratios, in assessing the severity of allergic reactions in patients with wasp venom allergy. A total of 61 patients with confirmed wasp venom allergy were categorized according to the Mueller scale, which classifies the severity of allergic reactions. Blood samples were analyzed for total and specific IgE levels, alongside a range of hematological and biochemical parameters. The study found significant differences in the EBLR and EBP/L indexes between patients with mild (Mueller I-II) and severe (Mueller III-IV) allergic reactions, with higher values indicating more severe responses. However, no significant differences were observed in other immune indexes, such as PLR, NLR, SII, and SIRI, or in additional blood parameters. These findings suggest that the EBLR and EBP/L ratios may serve as useful markers for predicting the severity of allergic re-actions in patients with wasp venom allergy. This is the first study to establish such a link, alt-hough further research with larger cohorts is necessary to confirm these results and their poten-tial application in clinical settings.

(1) Background: National health system databases represent one of the most obvious sources of information about epidemiology of adverse drug reactions including drug-induced allergy and anaphylaxis. (2) Methods: Retrospective analysis of data from national database of pharmacovigilance in the Russian Federation (analyzed period 02.04.2019 - 21.06.2023) was performed. The prevalence of anaphylactic reactions (ARs) was determined, the structure of drugs involved was estimated together with patients’ characteristics. (3) Results: ARs were reported in 8.3% of drug-induced allergic reactions (2304/27,727), mean age of patients was 48.2 ± 15.8 years, 53.2% were females. Main causative groups of drugs were antibiotics, ABs (44.62%), local anesthetics, (19.97%), and cyclooxygenase (COX)-inhibitors (10.07%). Fatal ARs was reported in 9.5% (218/2304), mean age 48.0 ± 16.7 years, 56.2% females. Pediatric population accounted for 5.8% (133/2304), mean age 11.8± 4.5 years, 51.9% females. Elderly population accounted for 2.8% (65/2304), mean age 73.0±5.3 years, 43.5% (27/65) females. ABs were the leading causative groups of ARs in the elderly (40%), children (42.86%), and among fatal cases (50%). (4) Conclusions: ARs accounted for 8.3% of all drug-induced allergic reactions, and ABs were the most common causative agents. Females predominated in all groups except elderly patients.

Abstract: Background: Cow’s milk allergy (CMA) is one of the most common and complex food allergies affecting children worldwide and with few exceptions, presents in the first few months of life. Baked milk containing diets are well tolerated in the majority of milk allergic children and allow dietary restrictions to be relaxed. In addition, the early introduction of tolerated forms of allergenic foods to the infant’s diet in small amounts may enhance the outgrowth of milk allergy through oral tolerance induction. The methods of milk introduction vary widely across the globe. Methods: We convened an expert group to develop a comprehensive milk ladder based on calculated milk protein content using Indian foods. To validate the milk ladder, foods chosen for the ladder were analyzed and the ladder was re-evaluated based on amount cooked milk protein content. Results: Combining expert consensus and validation of milk protein content, we created the world’s first milk ladder containing Indian foods. This is the first ladder that provides information on timing and temperature of cooking, with validated milk protein content. Conclusions: This is the first milk ladder based on unique features of Indian food habits built by consensus of Indian experts along with international collaboration with quantified of milk protein in each step. We believe the “The Indian Milk Ladder” will be a very helpful tool for pediatricians helping manage CMA in children as well as their parents and caregivers, not only in India but in countries world-wide where these foods are commonly consumed.

This manuscript provides a new integrated view of the development of allergen-specific TH2 and the lack of their associated Treg cells in a unified model, justifying the need for IL-2 to correct allergy conditions.

In this paper we aim to help topical probiotics research and development achieve its potential as an incredible future solution for skin problems by investigating whether the current products on the market satisfy criteria for safe and effective use on the skin microbiome. As previously defined, this includes whether they use microbes known to be part of a healthy skin microbiome and in healthy amounts. In addition, we evaluate whether they contain live microbes, and therefore can be classified as probiotics according to the WHO’s definition. Using recent market analysis at least 84% of products do not contain live microbes. Of the products that appeared to use live microbes, they contained those used in research and development of probiotics for the gut. Due to the varying composition of each person’s microbiome, there is not a one size fits all probiotic solution. Personalisation of probiotics products is essential to satisfy the criteria for safe and effective use, but none of the products on the market, understandably, offer this. Upsetting the delicate ecosystem balance of the skin microbiome could have damaging effects and regulation could help to stop a loss of trust between consumers and cosmetics industry. Future work will perform an in-depth evaluation of the topical probiotics on the market in the EU, USA, and Canada. We will also investigate how to move the topic closer to achieving its potential by updating the criteria, including by discussing how to measure the success of a probiotic solution.

Background: Preterm birth is a major cause of morbidity and mortality in infants and children. Non-invasive methods for screening the neonatal immune status are lacking. Archaea, a prokaryotic life domain, comprise methanogenic species that are part of the neonatal human microbiota and contribute to early immune imprinting. However, they have not yet been characterized in preterm neonates. Objective: To characterize the gut immunological and methanogenic Archaeal (MA) signature in preterm neonates, using the presence or absence of atopic conditions at the age of 1 year as a clinical endpoint. Methods: Meconium and stool were collected from preterm neonates and used to develop a standardized stool preparation method for the assessment of mediators and cytokines and characterize the qPCR kinetics of gut MA. Analysis addressed the relationship between immunological biomarkers, Archaea abundance, and atopic disease at age 1. Results: Immunoglobulin E, tryptase, calprotectin, EDN, cytokines, and MA were detectable in the meconium and later samples. Atopic conditions at age 1 year were positively associated with neonatal EDN, IL-1β, IL-10, IL-6, and MA abundance. The latter was negatively associated with neonatal EDN, IL-1β and IL-6. Conclusion: We report a non-invasive method for establishing a gut immunological and Archaeal signature in preterm neonates, predictive of atopic diseases at the age of 1 year

Atopic dermatitis (AD) is a chronic and allergic skin disease, however, there is no cure for the disease. Many studies have shown anti-AD potentials of red ginseng, while red ginseng marc (RGM) remained after the ginseng extraction is discarded as industrial waste. However, it is recently reported that RGM, particularly fermented RGM (fRGM), still contains the bioactive properties. Thus, anti-allergic effects of fRGM were examined in 2,4-dinitrochlorobenzene-induced AD-like mice model. The model was topically treated with distilled water (control), dexamethasone, or fRGM for six weeks. The treatments of fRGM alleviated the skin lesions and reduced serum IgE levels, compared with the control. The fRGM also reduced skin levels of lipid peroxidation and superoxide anion, however, increased glutathione contents, with down-regulated gene expressions for inflammatory mediators. The histopathological analyses demonstrated that fRGM suppressed the epidermal thickening, collagen deposition, and inflammatory cell and mast cell infiltration, which involved the anti-inflammatory, anti-oxidant, and anti-apoptotic effects. Further, fRGM suppressed hypertrophic changes and inflammatory responses in the spleen and lymph node. The beneficial effects were observed in the dexamethasone and fRGM groups, however, the antioxidant effects were evident only in the fRGM treatments. These provide useful information for developing fRGM as therapeutic sources for AD.

Specific nutrients including n-3 long chain polyunsaturated fatty acids (LCPUFAs), flavonoids, vitamin A, D and E are considered to possess protective properties on human health by impacting on immunological reactions. An ‘inflammation-suppressive’ effect appears to be the common denominator of the beneficial effects of most of these dietary components which may protect against the development of chronic immune disorders such as allergy. However, the majority of these promising data are from preclinical studies such as animal disease models, as the majority of clinical studies only indicate associations. PUFAs, especially n-3 LCPUFAs, have been shown to interact with both the sensitization as well as the effector phase in food allergy. However, it should be noted and realised that PUFAs are highly susceptible to lipid oxidation. Flavonoids and fat-soluble vitamins both contain anti-inflammatory properties and are able to act as anti-oxidants as well. Here, we explore the anti-allergic properties of PUFAs, flavonoids and fat-soluble vitamins in order to create an overview and, more importantly, suggest a strategy to target food allergies using these components and combinations thereof. Dietary n-3 LCPUFAs and the above mentioned micronutrients are promising anti‐allergy agents capable of influencing the allergic immune response through multiple and different biological pathways.

Furthermore, the nasal congestion typical of rhinitis can contribute to upper airway obstruction and sleep-disordered breathing. A vicious circle is created between asthma and sleep-disordered breathing: uncontrolled asthma and sleep-disordered breathing can worsen each other. In children with genetic obesity, despite alterations in the immune system, fewer allergies are found compared to the general population. The causes of this reduced allergenicity are unclear but probably involve genetic, immunological, and environmental factors. Further studies are needed to understand the mechanisms. The study emphasizes the importance of jointly evaluating and managing allergies, obesity, and sleep-disordered breathing in children, considering their close interconnection.

Cow’s Milk (CM) is a healthy food consumed worldwide by individuals of all ages. Unfortunately, 'lactase deficient' individuals cannot digest milk's carbohydrate lactose depriving themselves of highly beneficial milk proteins like casein, lactoalbumin and lactoglobulin, due to lactose intolerance (LI), while other individuals develop cow milk allergy specifically against these proteins (CMPA). The management of these conditions is distinctly different and an inappropriate diagnosis or treatment may have significant implications for the patients, especially if they are infants or very young children, resulting in unnecessary dietary restriction or avoidable adverse reactions. Omics technologies play a pivotal role in elucidating the intricate interactions between nutrients and the human body, spanning from genetic factors to the microbiota profile and metabolites. This comprehensive approach enables the precise delineation and identification of distinct cohorts of individuals with specific dietary requirements, so that tailored nutrition strategies can be developed. This is what is called personalized nutrition or precision nutrition (PN), the area of nutrition that focuses on the effects of the nutrients over the genome, proteome and metabolome, promoting well-being and health, preventing diseases, reducing chronic disease incidence, and so increasing life expectancy. Here, we report the scientific community opinion proposing to replace the approach “one size fits all” with tailor-made nutrition programs, designed by integrating nutrigenomic data together with clinical parameters and microbiota profiles, taking into account the individual lactose tolerance threshold and needs in terms of specific nutrients intake. This customized approach could help LI patients to improve their quality of life, overcoming depression or anxiety, often resulting from the individual perception of this condition as different from a normal state.

Objective: To determine the effect of birth season climate on adult total serum IgE (TSIgE) levels. Study design: The study is a retrospective chart review with the following inclusion criteria: TSIgE measurement, age ≥16, and northeastern Tennessee birthplace. Main outcome measures include TSIgE levels, birth season climatic conditions, and regional pollen-producing plant and pollen counts. Results: The records of 1,274 women (mean age 40.8 ± 17.5, age range 16-96) and 762 men (mean age 38.1 ± 17, age range 16-82) seen in our Allergy Clinic were reviewed. Persons born in the spring and summer, the seasons with the highest pollen counts and the most favorable climatic conditions for plant growth, had nearly twice the odds of having TSIgE levels >1σ above the mean of the study group when compared to those born in the fall or winter (odds ratio (OR) 1.75, 95% confidence interval (CI) 0.96-3.17 and OR 1.93, 95% CI 1.04-3.57, respectively); odds were highest for those born in March (OR 2.55, 95% CI 1.37-4.74) and July (OR 2.38, 95% CI 1.25-4.51) and lowest for those born in November (OR 0.11, 95% CI 0.0068-1.79). When averaged over the 95-years of study and five 30-year climate cycles TSIgE levels increased linearly as the seasons progressed from fall to summer (r²= 0.9475, P=0.0266). Of the climatic factors, TSIgE levels correlated most strongly with levels of precipitation (r²= 0.9145, P=0.0437). Conclusion: Climatic conditions that increase birth season exposure to environmental allergens may have a life-long effect on TSIgE production.

The yellow-legged Asian hornet (Vespa velutina Lepeletier 1836 (Hymenoptera: Vespidae)) is naturally distributed in China, Southeast Asia and India; however it has since detected outside of its native area, confirmed as being established in South Korea, Europe and Japan. Health risks and deaths caused by the invasive Vespa velutina stings have become a public health concern, being the most common cause of anaphylaxis due to hymenopterans in some European regions. This in turn has led to increased demand from medical practitioners and researchers for Vespa velutina venom for diagnostic and therapeutic purposes. In this study, a straightforward, quick and inexpensive method for obtaining Vespa velutina venom by electric stimulation is described. The venom extracts were analyzed by nuclear magnetic resonance spectroscopy (1H-NMR), confirming the composition of the obtained material. The availability of Vespa velutina venom will lead to improved diagnostic and therapeutic methods, mainly by venom immunotherapy (VIT), in patients allergic to this invasive species.

The post-hoc analysis presented here aimed to address the influence of endogenous vitamin D in the immunological mechanism underlying effective mite allergoid-immunotherapy (AIT). Previously, we have shown that one subpopulation of T regulatory cells results in phenotypically identifiable as functionally potentiated and memory cells in allergic children after 12 months of this immunoactive treatment. Indeed, AIT is the only known treatment able to reshape the detrimental immune response against the allergen into a not noxious one. Besides, VD is widely considered an immunoregulatory molecule endogenously produced and exogenously provided with foods and supplements that might interact with AIT mechanism and affect its outcome. Therefore, a post-hoc analysis of the clinical and immunological data of three different cohorts of allergic patients was performed. One cohort (N=70) was on standard symptoms-controlling pharmacological treatment while the other two (N=60 and N=35, respectively) were treated with AIT for 12 months. Among the first were observed a lower mean endogenous VD level (&lt;22 ng/ml) along with worse symptoms and higher use of medications. Remarkably, the comparison between two sub-cohorts of patients with serum VD above (N=32) or below (N=28) a cut-off value set at mean value (27 ng/ml) revealed that optimal improvement of all clinical and immune parameters was achieved (as expected by effective AIT), irrespective of the VD level. Notably, the third analysis, carried out on one cohort of AIT patients also taking concomitantly VD3 as food supplement (N=19), was distinguished by uppermost overall treatment outcome (amelioration of symptoms, lowest medications requirement, and reduction of total and allergen-specific IgE) as well as the increase of allergen-specific tolerogenic memory T regulatory cells. These findings suggest that endogenous VD level affects allergy severity and allergen immunotherapy effectiveness. Also, VD3 might be investigated as an add-on supplement to get the best out of immunotherapy in VD deficient/insufficient allergic patients. The immunogenic but low-allergenic mite allergoid used as bioactive agent might have contributed to minimize allergic and highlight immunological effects described here.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with high prevalence worldwide, including countries from Asia, Africa and Latin America, and in different ethnic groups. In recent years, more attention on AD heterogeneity associated on multiple factors, including patient’s ethnic background, has been posed, resulting in an increasing body of clinical, genetic, epidemiologic, and immune-phenotypic evidence that delineate differences among racial groups with AD. Filaggrin (FLG) mutations, the strongest genetic risk factor for the development of AD, are detected in up to 50% of European and 27% of Asian AD patients, while very rarely in Africans. The Th2 activation is a common attribute of all ethnic groups, though the Asian endotype of AD is also characterized by an increased Th17-mediated signal whereas African Americans own a strong Th2/Th22 signature and the absence of Th1/Th17 skewing. In addition, the ethnic heterogeneity may own important therapeutic implications as the genetic predisposition may affect treatment response and, thereby, a tailored strategy that better targets the dominant immunologic pathways in each ethnic subgroup may be envisaged. Nevertheless, white patients with AD represent the largest ethnicity enrolled and tested in clinical trials and the most treated in a real-world setting, limiting the investigation about safety and efficacy across different ethnicities. The purpose of this review is to describe the heterogeneity of pathophysiology across ethnicities and its potential therapeutic implications.

Acrylates and methacrylates are widely used, especially in the dental industry, but can cause adverse skin reactions. These compounds, including 2-hydroxyethyl methacrylate, triethylene glycol dimethacrylate, and bisphenol A-glycidyl methacrylate, are strong contact irritants or allergens. Found in dental prostheses, composite resins, dentin bonding materials, and glass ionomers, they pose a higher risk of exposure for dental personnel. Clinically, acrylate allergies manifest as facial rashes, eczema with cracked skin on fingers (pulpitis), nail dystrophy, and periungual dermatitis. Recently, the highest frequency of allergic reactions to acrylates has shifted from dentistry to the beauty industry due to increased use in artificial nails, eyelashes, and hair extensions. This has led to greater sensitization. Acrylates are also used in medical applications, such as bone cement for orthopedic endoprostheses, soft contact lenses, hearing aids, histological preparations, and wound dressings, which can also cause allergic reactions. Severe dermatitis from surgical glue containing acrylates has been documented, and diabetic medical devices are potential sources of allergic contact dermatitis. Given the extensive use and prolonged skin contact of products containing acrylates and methacrylates, this review aims to present current knowledge and literature on reactions to these compounds across different industries.

Hazelnut, pistachio and cashew are tree nuts with health benefits but also with allergenic properties being prevalent food allergens in Europe. The allergic characteristics of these tree nuts after processing combining heat, pressure and enzymatic digestion were analyzed through in vitro (Western blot and ELISA) and in vivo test (Prick-Prick). In the analyzed population, the patients sensitized to Cor a 8 (nsLTP) were predominant over those sensitized against hazelnut seed storage proteins (Sprot, Cor a 9 and 14), which displayed higher IgE reactivity. The protease E5 effectively hydrolyzed proteins from hazelnut and pistachio, while E7 was efficient for cashew protein hydrolysis. When combined with pressured heating (autoclave and Controlled Instantaneous Depressurization (DIC)), these proteases notably reduced the allergenic reactivity. The combination of DIC treatment before enzymatic digestion resulted in the most effective methodology to drastically reduce or indeed eliminate the allergenic capacity of tree nuts.

Background: The Coronavirus Disease 2019 (COVID-19) pandemic presented a new challenge in modern medicine. The development of vaccines was followed by massive population vaccinations. A few reports on post-vaccination allergic reactions have made patients and medical personnel uneasy as to anti-COVID-19 vaccines’ allergising potential. Most of the studies in this area to date have been small, and some that were based on global databases skipped most of the allergic diseases and concentrated only on anaphylaxis. We aimed to analyse the incidence of serious allergic reactions based on the EudraVigilance (EV) database, regardless of the reported symptoms and allergy mechanism. Methods: The total number of administrated vaccine doses was extracted on the 5th October 2023 from Vaccine Tracker and included all administrations since vaccinations began in the European Economic Area (EEA). Data on serious allergic reactions to COVID-19 vaccines was extracted from the EudraVigilance database with the same time point. The code names of 147 allergic symptoms or diseases were used. Results: The frequency of serious allergic reactions per 100,000 administered vaccine doses was 1.53 for Comirnaty, 2.16 for Spikevax, 88.6 for Vaxzevria, 2.11 for Janssen, 7.9 for Novavax, 13.3 for VidPrevtyn Beta and 3.1 for Valneva. The most prevalent reported reactions were oedema (0.46) and anaphylaxis (0.40). Only 6% of these reactions were delayed hypersensitivity-oriented. Conclusions: The overall frequency of potential serious allergic reactions to COVID-19 is very rare. Therefore, COVID-19 vaccines seem to be safe for human use. The lowest frequency of allergic reaction was observed for Comirnaty and the highest for Vaxzevria.

Inflammatory allergic and nonallergic respiratory pathologies often co-exist. The root cause is not clear. This paper demonstrates that it is ascribable to protons (H⁺) released into cells by exogenous and endogenous acids. The hypothesis of acids as the common cause stems from two considerations: a) it has long been known that exogenous acids present in air pollutants can induce the irritation of epithelial surfaces, particularly the airways, inflammation and bronchospasm; b) according to recent articles, endogenous acids, generated in cells by phospholipases, play a key role in the biochemical mechanisms of initiation and progression of allergic responses. Therefore, the intracellular acidification and consequent Ca²⁺ increase, induced by protons generated by either acid pollutants or endogenous phospholipases, may be the causal mechanism of the multimorbidity of these diseases, and environmental acidity may contribute to their spread.

Our study examines the association of the presence of mildew, cockroaches, and pets in homes as well as household dust allergens with the prevalence and/or severity of allergic diseases. No study has concurrently assessed home environment exposures in relation to allergic conditions in the general US population. Data from 5,409 participants from the 2005-2006 National Health and Nutrition Examination Survey living in their current homes for ≥1 year were analyzed. Multivariate logistic regression analyses between home exposures and allergic diseases prevalence and severity were performed. In adjusted analyses, mildew was associated with higher current asthma, allergies, and allergic rhinitis prevalence; endotoxin, with higher current asthma prevalence), and dust Canis familiaris (Can f) 1, with higher allergic rhinitis prevalence. However, presence of cockroaches and dust Dermatogoides farinae (Der f) 1 were associated respectively with lower current asthma and allergies prevalence. Presence of mildew, dust Der f1, Dermatogoides pteronyssinus (Der p) 1, Feline domesticus (Fel d) 1, and endotoxin were all associated with asthma and/or wheeze severity. Non-atopic asthma was more frequent with mildew and/or musty smell dust and higher dust Fel d1 concentration, while atopic asthma was more prevalent with higher Can f1and endotoxin concentrations in dust. This study confirms previous relationships and reports novel associations, generating hypotheses for future research.

Epithelial characteristics underlying the differential susceptibility of chronic asthma to SARS-CoV-2 (COVID-19) and other viral infections are currently unclear. By revisiting transcriptomic data from patients with Th2 low versus Th2 high asthma, as well as mild, moderate and severe asthmatics, we characterized the changes in expression of human coronavirus and influenza viral entry genes relative to sex, airway location and disease endotype. We found sexual dimorphism in expression of COVID-19 genes ACE2, TMPRSS2, TMPRSS4, and SLC6A19. ACE2 receptor downregulation occurred specifically in females in Th2 high asthma, while proteases broadly assisting coronavirus and influenza viral entry, TMPRSS2 and TMPRSS4, were highly upregulated in both sexes. Overall, changes in COVID-19 gene expression were specific to Th2 high molecular endotype of asthma, and different by asthma severity and airway location. The downregulation of ACE2 (COVID-19, SARS) and ANPEP (HCoV-229E) viral receptors correlated with loss of club and ciliated cells in Th2 high asthma, while the increase in DPP4 (MERS-CoV), ST3GAL4, and ST6GAL1 (influenza) associated with an increase in goblet and basal activated cells. Overall, this study elucidates sex, airway location, disease endotype and changes in epithelial heterogeneity as factors underlying asthmatic susceptibility, or lack thereof, to COVID-19.

Proteomics in respiratory allergic diseases has such a battery of techniques and programs that one would almost think that there is nothing impossible to find, invent or mold. All these resources that we document here, are involved in solving problems in allergic diseases, both diagnostic, prognostic, treatment and immunotherapy development. The main perspectives, according to this version, are in three strands and / or lockout immunological system: 1) In blocking the diapedesis of cells involved, 2) modifications and blocking of paratopes and epitopes being understood by modifications to antibodies, antagonism or blocking them and 3) blocking FcεR1 receptors to prevent specific IgEs from sticking to mast cells and basophils. These tools and targets in the allergic landscape are, in our view, the prospects in the field.

Food processing can modify protein biochemical properties altering its immunoreactivity and allergenicity. Resistance to enzymatic digestion is one of the main characteristics of food allergens, specially to pepsin and trypsin. In this work, the aim is to compare the digestomes of raw and heat and /or pressured treated peanuts, hazelnut, pistachio and cashew resulting from the INFOGEST harmonized digestion protocol, as well as the different behaviour regarding IgE-binding capacity, by means of in vitro analysis. Protein patterns, resolved by SDS-PAGE, were assayed with sera from allergic patients and confirmed by competitive ELISA in hazelnut and peanut. The results of our study reveal that different processing methods affect differently gastrointestinal (GI) digestion of peanut, hazelnut, pistachio and cashew allergens. Simulated GI digestion led to extensive de-struction of the protein structure, reducing but not abolishing the IgE reactivity of peanut, ha-zelnut, pistachio and cashew allergenic proteins. Boiling for 60 minutes did not affect the protein profile of these nuts, although enzymatic activity was stimulated, decreasing the IgE binding capacity. When heat and pressure was applied to these nuts, simulated digestion promoted an almost complete inhibition of the allergenic potential.

To increase the prediction accuracy of positive oral food challenge (OFC) outcome during stepwise slow oral immunotherapy (SS-OIT) in children with hen’s egg (HE) allergy, we evaluated the predictive value of the combination of antigen-specific IgE (sIgE) with antigen binding-avidity and sIgG4 values. Sixty-three children with HE allergy undergoing SS-OIT were subjected to repeated OFC with HE. We measured the ovomucoid (OVM)-sIgE by ImmunoCAP or densely carboxylated protein (DCP) microarray, sIgG4 by DCP microarray, and the binding-avidity of OVM-sIgE defined as the level of 1/ IC50 (nM) measured by competitive binding inhibition assays. The OFC was positive in 37 (59%) patients undergoing SS-OIT. Significant differences in DCP-OVM-sIgE, CAP-OVM-sIgE, I/ IC50, DCP-OVM-sIgG4, the multiplication products of DCP-OVM-sIgE and binding-avidity of DCP-OVM-sIgE (DCP-OVM-sIgE/IC50) and DCP-OVM-sIgE/sIgG4 were compared between the negative and positive groups (p<0.01). Among them, the variable with greatest area under the receiver operating characteristic curve was DCP-OVM-sIgE/IC50 (0.84), followed by DCP-OVM-sIgE/sIgG4 (0.81). DCP-OVM-sIgE/IC50 and DCP-OVM-sIgE/sIgG4 are potentially useful markers for the prediction of positive OFC during HE-SS-OIT and may allow proper evaluation of the current allergic status in the healing process during HE-SS-OIT

Brachycephalic dogs are not only affected by brachycephalic obstructive airway syndrome (BOAS), but also comprise up to 30% of canine patients seen by veterinary dermatologists, with English Bulldogs and Pugs particularly overrepresented. Some skin diseases are associated with the abnormal anatomic conformation of brachycephalic dogs, while for others there is a underlying genetic basis or a general predisposition. Anatomic alterations associated with brachycephaly, leading to fold formation of the skin and stenosis of the ear canal, together with primary immunodeficiencies described in some breeds, favor the development of pyoderma, Malassezia dermatitis and otitis externa/media. Frequently neglected but often lifelong dermatological problems of brachycephalic dogs are an important consideration when discussing genetic and medical conditions affecting the welfare of those dogs. Here we review the current state of knowledge concerning dermatological problems of brachycephalic dogs, and combine it with clinical experience in the management of these challenging disorders.

The diagnosis and management of cow's milk allergy (CMA) is a topic of debate and controversy. We aimed to compare the opinions of expert groups from the Middle East (n=14) and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n=13). These Expert groups voted on statements developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared. Overall, there was consensus amongst both groups of experts. Most experts agreed that symptoms of crying, irritability and colic, as single manifestations, do not suggest CMA. They agreed that amino-acid-based formula (AAF) should be reserved for severe cases (e.g. malnutrition and anaphylaxis) and that there is insufficient evidence to recommend a step-down approach. There was no consensus on the statement that a cow’s milk-based extensively hydrolysed formula (eHF) should be the first choice as a diagnostic elimination diet in mild/moderate cases. Although the statements regarding the role of hydrolysed rice formula as a diagnostic and therapeutic elimination diet were accepted, 3/27 disagreed. The votes regarding soy formula highlight the differences in opinion in the role of soy protein in CMA dietary treatment. Generally, soy-based formula is seldom available in the Middle East region. All ESPGHAN experts agreed that there was no added value of probiotics, prebiotics, and synbiotics to the efficacy of elimination diets, whereas 3/14 of the Middle East group thought there was sufficient evidence. Therefore, there is not a consensus on the optimal diagnostic and therapeutic elimination diet for CMA, but the first-choice elimination diet and the stepwise management approach reveal some differences.

Background: allergic diseases and, in particular food allergy (FA), have been identified as one of the major diseases in the world. The first 1000 days of life can be a “window of opportunity” or a “window of susceptibility” during which several factors can predispose children to FA development. Changes in gut microbiota composition, from pregnancy to infancy, could have a pivotal role in this regard: some bacterial genus such as Lactobacillus or Bifidobacterium seem to be protective from FA development, on the contrary Clostridium and Staphylococcus appear to be unprotective. Methods: we conducted a research through the most recent literature (2013-2023), using Pubmed and Scopus as databases. We included English original papers, clinical trials, metanalysis and reviews. Case reports, series and letters have been excluded. Results: during pregnancy, maternal diet can play a fundamental role in influencing gut microbiota composition of newborns. After birth, human milk can promote the development of protective microbial species by human milk oligosaccharides (HMOs), that play a prebiotic role. Also complementary feeding can modify gut microbiota composition. Conclusions: the first two years of life are a critical period where several factors, in genetic predisposed children, can increase the risk of FA development.

One mechanism by which fructose could exert deleterious effect in metabolism and inflammation is via its potency vis-à-vis de Maillard reaction. We employed simulated stomach and duodenum digestion of ovalbumin to test the hypothesis that indeed AGEs are formed by fructose during simulated digestion of an ubiquitous food protein with intrinsic allergenic potential and under model physiological conditions. Methods: OVA was subjected to simulated gastric and intestinal digestion using standard models, in presence of fructose or glucose (0-100 mM). Peptide fractions were analyzed by fluorescence spectroscopy and intensity at Excitation: λ370 nm, Emission: λ 440nm. Results: AGE adducts form between fructose and OVA which can be found in peptide fractions (< 5 kDa) at times (30 min) and concentration ranges (10 mM) plausibly found in the intestines, whereas no reaction occurs with glucose. The reaction is inhibited by chlorogenic acid at concentrations compatible with those found in the gut. The reaction is inhibited by AG, a specific antiglycation agent. Conclusion: Our proof of principle study shows that fructose-AGE formation on an ubiquitous allergenic protein indeed occurs in one hour and thereby may pave the way for the study of yet another mechanism by which the excess fructose in our Western diets is contributing to disease: intestinal AGE formation, absorption and RAGE engagement.

We set up this preliminary study to evaluate one main question: could strengthening the microbiome have potential benefits for patients suffering with adverse effects after stopping long term topical steroid use? We aim to turn it into a much larger study if the results show promise. After commonly being prescribed for eczema, cessation of topical steroid use, especially after long periods of inappropriate use, can leave lasting adverse effects on the body and skin, known by some as topical steroid withdrawal (TSW). Furthermore, the subsequent withdrawal the body experiences when coming off the drug can leave lasting adverse effects on the body and skin, known by some as topical steroid withdrawal (TSW). This preliminary study involved seven human participants suffering with skin problems associated with TSW who approached Dr. Anja Gijsberts-Veens of their own volition because they were interested in more natural recovery methods. Five completed the study in full. Progress in skin condition was tracked by self-assessed symptom severity questionnaires filled out at the beginning and end of the study. The skin microbiome was addressed by using a 100% natural product shown in previous work to significantly increase skin microbiome biodiversity. Three participants implemented dietary changes and supplementation in response to guidance after fecal sample analysis to improve their gut health and biodiversity. The average improvement in skin symptoms for all participants was 40% and average symptom improvement ranged from 14% for Patient 5 to 92% for Patient 1. On average, the participants saw an improvement in 85% of their symptoms and a stagnation or regression in 11% and 4% respectively. We believe these results show enough promise to warrant expansion of this research to use a larger sample size, preferably 50+ participants, in future work. We also aim to swab the skin of participants to assess the effect on the skin microbiome from skin and gut treatments, as well as including more in-depth analysis of skin and gut microbiomes.

Food allergies are common worldwide and have become a major public health concern; more than 220 million people are estimated to suffer from food allergies worldwide. On the other hand, polyphenols, phenolic substances found in plants, have attracted attention for their health-promoting functions, including their anti-allergic effects. In this study, we examined the potential inhibitory effects of 80% ethanol extracts from 22 different vegetables on the degranulation process in RBL-2H3 cells. Our aim was to identify vegetables that could prevent and treat type I allergic diseases. We found strong inhibition of degranulation by the extracts of perilla and chives. Furthermore, we verified the respective efficacy via animal experiments, which revealed that the anaphylactic symptoms caused by ovalbumin (OVA) load were alleviated in OVA allergy model mice that ingested vegetable extracts of perilla and chives. These phenomena were suggested to be caused by induction of suppression in the expression of subunits that constitute the high-affinity IgE receptor, particularly the α-chain of FcεR I. Notably, the anti-allergic effects of vegetables that can be consumed daily are expected to result in the discovery of new anti-immediate allergenic drugs based on the components of these vegetables.

As described in previous work, the use of synthetic chemical ingredients in modern cosmetics is postulated to be a cause of damage to the skin microbiome. The discovery that biodiversity on the human skin is currently the only reliable indicator of skin health, meant that for the first time, a mechanism to test for healthy skin was possible. Using this mechanism and in collaboration with The Medical University of Graz, who carried out the independent study, this work aimed to help answer whether modern day synthetic cosmetics are a main cause of long term damage to the skin microbiome. Thirty-two human participants tested three different face washes for their effect on the skin’s microbial diversity, along with skin pH, moisture and TEWL (trans-epidermal water loss), washing twice a day for four weeks. The upper volar forearm of the volunteers was swabbed at the beginning, two weeks in and end (four weeks). 16S rRNA sequencing was used. One leading ‘natural’ brand full of synthetic ingredients, a leading synthetic brand and a 100% natural face wash were used. Results give the first indications of a link between synthetic ingredients in a cosmetics product, and its effect on skin microbiome biodiversity. It paves the way for future studies on the topic with a larger sample group, longer test period and standardised methodology to create a universal standard for testing the health of skin using benchmark diversity values. This can be used in the future to test the effectiveness of cosmetics or ingredients on skin health, leading to the banning of products proven to harm the skin’s natural environment.

The development of rapid analysis of human serum for the presence of allergen-specific IgE is currently important. Consequently, we developed two types of 3D protein biochips. The first one is a 3D hydrogel biochip containing hydrogel droplets with protein molecules (allergens, immunoglobulins and others). These droplets are disposed on elements consisting of short polymer brushes grafting from a surface of polybutylene terephthalate polymer. The immobilization of proteins was induced by short-wave UV radiation. On such a biochip, the kinetics of allergen-sIgE complex formation reached 70% of saturation for 6 hours. Also we developed a 3D brush microchip containing on the surface of a polyethylene terephthalate polymer the brush elements with protein molecules covalently immobilized by opening oxirane cycles by amino and thiol nucleophilic groups contained in proteins. In the case of 3D brush microchip the kinetics of allergen-sIgE complex formation reached 100% of saturation for 3 hours, and fluorescent signals were 2-3 times higher than those of the 3D hydrogel biochip. Thus, the comparative analysis revealed that 3D brush biochips are more useful for further studies of protein-protein interactions than 3D hydrogel ones.

There is a skin allergy epidemic in the western world, and the rate of deterioration has increased significantly in the past 5-10 years. It is probable that there are many environmental contributing factors, yet some studies have linked it primarily to the rise in the use of synthetic chemical ingredients in modern cosmetics. Our challenge, therefore, was to find a mechanism to determine the effect these substances have on skin health, and whether they really are a primary cause of long term damage to the skin. The first problem is the lack of any definitive way to measure skin health. Motivated by the overwhelming evidence for a link between deficient gut flora and ill health, we decided to look at whether our skin microbiota could similarly be used as an indicator of skin health. Our research illustrates how it is microbiota diversity alone that can predict whether skin is healthy or not, after we revealed a complete lack of conclusive findings linking the presence or abundance of particular species of microbe to skin problems. This phenomenon is replicated throughout nature, where high biodiversity always leads to healthy ecosystems. ‘Caveman’ skin, untouched by modern civilisation, was far different to ‘western’ skin and displayed unprecedented levels of bacterial diversity. The less exposed communities were to western practices, the higher the skin diversity, which is clear evidence of an environmental factor in the developed world damaging skin. For the first time we propose benchmark values of diversity against which we can measure skin to determine how healthy it is. This gives us the ability to be able to predict which people are more likely to be prone to skin ailments, and start to test whether cosmetic ingredients and products are a main cause of the skin allergy epidemic.

A catastrophic loss of microbial biodiversity on the skin has led to alarming increase in the prevalence of allergies and long-term damage to the skin, which could also have damaging knock on effects to overall health. This study uses 50 human participants, to obtain an average (benchmark) value for the biodiversity of ‘healthy’ western skin, which is crucial in updating our 2017 skin health measuring mechanism to use standardised methodology. Previous work with a larger sample size was unsatisfactory for use as a benchmark due to its use of different and outdated diversity indices. We also investigated the effect of age and sex, two known skin microbiome affecting factors. Although no statistical significance is seen for age- and sex- related changes in diversity, there appear to be changes related to age which elaborates on previous work which used larger, more general age ranges. Our study indicates adults age 28-37 have highest diversity, and age 48-57 the lowest. Crucially, because of this study we are now able to update the skin health measuring mechanism from our 2017 work. This will aid diagnostic assessment of susceptibility to cutaneous conditions or diseases, and treatment. Testing any human subject will be rapidly improved by obtaining future benchmark diversity values for any age, sex, body site and area of residence, to which they can be compared. This improvement means we can also more accurately investigate the ultimate question: What factors in the western world are a main cause of the skin allergy epidemic? This could lead to future restriction of certain synthetic chemicals or products found to be particularly harmful to the skin.