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Background: Pediatric cow milk allergies (CMA) can occur in immunoglobulin (Ig) E and non-IgE-mediated forms. Unlike IgE-mediated allergies, the mechanisms of disease pathogenesis in non-IgE-mediated food allergy and an association with microbiome has not been well established. Previous studies have identified the presence of altered humoral responses to gut bacteria in IgE mediated allergies. Here, we analyzed IgA, IgE and IgG responses to gut bacteria in subjects with either IgE or non-IgE mediated CMA to identify relative proportions of Ig-coated bacteria and characterize unique disease specific microbial signatures. Methods: Multi-parametric flow cytometry analysis was used to identify IgA, IgE and IgG responses to gut bacteria in CMA patients. Cell sorting of Ig coated gut bacteria was subsequently performed followed by high throughput 16S rRNA gene sequencing and specific patterns of humoral responses to gut bacteria assessed in each study group. Results: We identified significant alterations in IgA and IgG gut bacterial coating patterns in CMA subjects. Proportions of IgA-coated bacteria were decreased in IgE mediated CMA subjects without atopic dermatitis (ALL) and non-IgE mediated CMA subjects (ENP), compared to healthy controls (CON). In comparison, IgG-coated bacteria was significantly elevated in CMA subjects with atopic dermatitis (AD). Alpha and beta diversities displayed significant differences in IgA-, IgE-, and IgG-coated bacteria in AD and ENP groups. Significant differences in bacteria coated by IgA, IgE and IgG were detected at Phyla, Genus and Species levels and associated bacterial dysbiosis in IgE and non-IgE mediated allergies were identified. Linear discriminant analysis (LDA) effect size (LEFse) revealed unique disease associated bacterial signatures, including several pathogenic bacteria namely Bacteroides fragilis, Ruminococcus gnavus, Eubacterium dolichum, Fusobacterium, Clostridium neonatale and Robinsoniella peoriensis. Receiver operating characteristic curve analysis confirmed the efficiency of using the bacterial signatures identified as biomarkers for disease. Conclusions: Altered IgA and IgG responses to gut bacteria were identified in CMA subjects. The disease-specific responses were associated with alterations in bacterial diversity and concomitant dysbiosis of Ig-coated bacteria in IgE-mediated and non-IgE-mediated CMA pediatric subjects. The identification of pathogenic bacteria uniquely associated with different classes of allergic disease indicates a role of these bacteria in driving disease-specific pathological phenotypes. [ABSTRACT FROM AUTHOR]

Background Aim Methods Results Conclusion The role of autoimmune IgE responses in atopic dermatitis (AD) is highly debated. While IgE targeting self‐proteins has been extensively studied, IgE responses induced by human‐homologous exogenous molecular allergens (HEMAs) remains less understood.To investigate whether IgE antibody responses to HEMAs are associated with AD, its severity, and response to dupilumab.We enrolled 3325 participants with a history of allergic diseases, including 577 (17.3%) diagnosed with AD. Serum IgE antibodies against 183 exogenous allergenic molecules were measured using the IgE microarray (Allergy Explorer‐ALEX‐2®, MADX, Vienna). Based on international classification criteria, participants were stratified by AD severity and clinical phenotypes. For each patient, we developed an ‘IgE molecular‐mimicry index’ (IgE‐MMI), calculated from IgE reactivity to a panel of five HEMA protein families: arginine kinase, enolase (ENO), cyclophilin (CYP), lipocalin, and MnSOD. Logistic regression was employed to assess the association between IgE to HEMAs or IgE‐MMI and AD, its severity, and response to dupilumab.IgE sensitization to most HEMAs (32/48, 67%), but only to a small fraction of non‐HEMAs (3/135, 2.2%), was significantly more common in patients with severe AD compared to other patient groups. The IgE‐MMI was positive in 295/2748 (10.7%) of allergic patients without AD, and in 58/283 (20%), 52/134 (39%), and 86/160 (54%) of patients with remitting, moderate, or severe AD, respectively. It was strongly associated with specific phenotypes, such as flexural dermatitis (OR 8.4, 95% CI: 6.3–11.2), head and neck dermatitis (OR: 16.5, 95% CI: 7.4–37.2), and generalized eczema (OR: 8.6, 95% CI: 4.9–15.6). Poor response to dupilumab was associated with IgE antibodies to ENO (OR: 22.7, 95% CI: 1.7–302.9), but inversely associated with IgE antibodies to MnSOD (OR: 0.1, 95% CI: 0.02–0.8) and NPC‐2 from dust mites (OR: 0.1, 95% CI: 0.01–0.9).IgE microarrays are useful for broadly assessing IgE to HEMAs in allergic patients. IgE reactivity to HEMAs and a positive IgE‐MMI may serve as valuable biomarkers for severe AD, its clinical phenotypes, and the response to dupilumab. [ABSTRACT FROM AUTHOR]

Introduction: The basophil activation test (BAT) has shown evidence of high sensitivity and high specificity to support the diagnosis of IgE-mediated allergy. It is a functional test that uses live cells analyzed by flow cytometry and thus needs to be performed within 24h of blood collection. BAT has shown to be reproducible and reliable when tested in a clinical diagnostic laboratory with standardized protocols and flow cytometry settings. Areas covered: In this review, we summarize the evidence to support clinical use of BAT and the next steps required for clinical implementation for an improve clinical care for patients with suspected IgE-mediated food allergy. Expert opinion: BAT has recently been included in Clinical Guidelines of Food Allergy Diagnosis and its implementation in clinical practice depends largely on availability. Proposed clinical applications of the BAT include: distinction between food allergy and asymptomatic IgE sensitization; determination of food allergic status to peanut, tree nuts and seeds in polysensitized children; evaluation of tolerance to baked egg and baked milk in egg and milk allergic children; identification of patients at high-risk of severe allergic reactions; monitoring for spontaneous resolution of food allergy; confirmation of eligibility for specific treatments of food allergy; prediction and monitoring of response to immunomodulatory treatments. [ABSTRACT FROM AUTHOR]

The impact of human IgE glycosylation on structure, function and disease mechanisms is not fully elucidated, and heterogeneity in different studies renders drawing conclusions challenging. Previous reviews discussed IgE glycosylation focusing on specific topics such as health versus disease, FcεR binding or impact on function. We present the first systematic review of human IgE glycosylation conducted utilizing the PRISMA guidelines. We sought to define the current consensus concerning the roles of glycosylation on structure, biology and disease. Despite diverse analytical methodologies, source, expression systems and the sparsity of data on IgE antibodies from non‐allergic individuals, collectively evidence suggests differential glycosylation profiles, particularly in allergic diseases compared with healthy states, and indicates functional impact, and contributions to IgE‐mediated hypersensitivities and atopic diseases. Beyond allergic diseases, dysregulated terminal glycan structures, including sialic acid, may regulate IgE metabolism. Glycan sites such as N394 may contribute to stabilizing IgE structure, with alterations in these glycans likely influencing both structure and IgE‐FcεR interactions. This systematic review therefore highlights critical IgE glycosylation attributes in health and disease that may be exploitable for therapeutic intervention, and the need for novel analytics to explore pertinent research avenues. [ABSTRACT FROM AUTHOR]

The European Academy of Allergy and Clinical Immunology (EAACI) has released updated clinical guidelines for the diagnosis and management of IgE-mediated food allergy. The guidelines provide evidence-based recommendations for clinicians treating patients with suspected food allergies. The guidelines emphasize the importance of a detailed clinical history, including dietary history, in reaching an accurate diagnosis. They also outline various diagnostic tests, such as skin prick tests and specific IgE tests, and recommend oral food challenges when necessary. The guidelines also address management strategies, including dietary advice, treatment plans for allergic reactions, and the potential use of immunomodulatory treatments. [Extracted from the article]

Immunoglobulin E (IgE) plays a critical role for the immune system, fighting against parasites, toxins, and cancer. However, when it reacts to allergens without proper regulation, it can cause allergic reactions, including anaphylaxis, through a process initiated by effector cells such as basophils and mast cells. These cells display IgE on their surface, bound to the high-affinity IgE receptor FcεRI. A cross-linking antigen then triggers degranulation and the release of inflammatory mediators from the cells. Therapeutic monoclonal anti-IgE antibodies such as omalizumab, disrupt this process and are used to manage IgE-related conditions such as severe allergic asthma and chronic spontaneous urticaria. Interestingly, naturally occurring anti-IgE autoantibodies circulate at surprisingly high levels in healthy humans and mice and may thus be instrumental in regulating IgE activity. Although many open questions remain, recent studies have shed new light on their role as IgE regulators and their mechanism of action. Here, we summarize the latest insights on natural anti-IgE autoantibodies, and we compare their functional features to therapeutic monoclonal anti-IgE autoantibodies. [ABSTRACT FROM AUTHOR]

Summary: Despite the near ubiquitous presence of Ig‐based antibodies in vertebrates, IgE is unique to mammals. How and why it emerged remains mysterious. IgE expression is greatly constrained compared to other IgH isotypes. While other IgH isotypes are relatively abundant, soluble IgE has a truncated half‐life, and IgE plasma cells are mostly short‐lived. Despite its rarity, IgE is consequential and can trigger life‐threatening anaphylaxis. IgE production reflects a dynamic steady state with IgG memory B cells feeding short‐lived IgE production. Emerging evidence suggests that IgE may also potentially be produced in longer‐lived plasma cells as well, perhaps as an aberrancy stemming from its evolutionary roots from an antibody isotype that likely functioned more like IgG. As a late derivative of an ancient systemic antibody system, the benefits of IgE in mammals likely stems from the antibody system's adaptive recognition and response capability. However, the tendency for massive, systemic, and long‐lived production, common to IgH isotypes like IgG, were likely not a good fit for IgE. The evolutionary derivation of IgE from an antibody system that for millions of years was good at antigen de‐sensitization to now functioning as a highly specialized antigen‐sensitization function required heavy restrictions on antibody production—insufficiency of which may contribute to allergic disease. [ABSTRACT FROM AUTHOR]

Summary: Food allergies occur due to a lack of tolerance to the proteins found in foods. While IgE‐ and non‐IgE‐mediated food allergies have different clinical manifestations, epidemiology, pathophysiology, and management, they share dysregulated T cell responses. Recent studies have shed light on the contributions of different T cell subsets to the development and persistence of different food allergic diseases. This review discusses the role of T cells in both IgE‐ and non‐IgE‐mediated food allergies and considers the potential future investigations in this context. [ABSTRACT FROM AUTHOR]

Summary The etiology of allergy is closely linked to type 2 inflammatory responses ultimately leading to the production of allergen‐specific immunoglobulin E (IgE), a key driver of many allergic conditions. At a high level, initial allergen exposure disrupts epithelial integrity, triggering local inflammation via alarmins including IL‐25, IL‐33, and TSLP, which activate type 2 innate lymphoid cells as well as other immune cells to secrete type 2 cytokines IL‐4, IL‐5 and IL‐13, promoting Th2 cell development and eosinophil recruitment. Th2 cell dependent B cell activation promotes the production of allergen‐specific IgE, which stably binds to basophils and mast cells. Rapid degranulation of these cells upon allergen re‐exposure leads to allergic symptoms. Recent advances in our understanding of the molecular and cellular mechanisms underlying allergic pathophysiology have significantly shaped the development of therapeutic intervention strategies. In this review, we highlight key therapeutic targets within the allergic cascade with a particular focus on past, current and future treatment approaches using monoclonal antibodies. Specific targeting of alarmins, type 2 cytokines and IgE has shown varying degrees of clinical benefit in different allergic indications including asthma, chronic spontaneous urticaria, atopic dermatitis, chronic rhinosinusitis with nasal polyps, food allergies and eosinophilic esophagitis. While multiple therapeutic antibodies have been approved for clinical use, scientists are still working on ways to improve on current treatment approaches. Here, we provide context to understand therapeutic targeting strategies and their limitations, discussing both knowledge gaps and promising future directions to enhancing clinical efficacy in allergic disease management. [ABSTRACT FROM AUTHOR]

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

Epidemiological studies have explored the relationship between allergic diseases and cancer risk or prognosis in AllergoOncology. Some studies suggest an inverse association, but uncertainties remain, including in IgE‐mediated diseases and glioma. Allergic disease stems from a Th2‐biased immune response to allergens in predisposed atopic individuals. Allergic disorders vary in phenotype, genotype and endotype, affecting their pathophysiology. Beyond clinical manifestation and commonly used clinical markers, there is ongoing research to identify novel biomarkers for allergy diagnosis, monitoring, severity assessment and treatment. Gliomas, the most common and diverse brain tumours, have in parallel undergone changes in classification over time, with specific molecular biomarkers defining glioma subtypes. Gliomas exhibit a complex tumour‐immune interphase and distinct immune microenvironment features. Immunotherapy and targeted therapy hold promise for primary brain tumour treatment, but require more specific and effective approaches. Animal studies indicate allergic airway inflammation may delay glioma progression. This collaborative European Academy of Allergy and Clinical Immunology (EAACI) and European Association of Neuro‐Oncology (EANO) Position Paper summarizes recent advances and emerging biomarkers for refined allergy and adult‐type diffuse glioma classification to inform future epidemiological and clinical studies. Future research is needed to enhance our understanding of immune–glioma interactions to ultimately improve patient prognosis and survival. [ABSTRACT FROM AUTHOR]

Background: Recurrent oral erythema multiforme (ROEM) is an uncommon subtype of erythema multiforme. Immunoglobulin E (IgE) is essential in acute allergy reactions and chronic allergic inflammatory disorders. Purpose: This report aims to describe the advantages of total IgE screening for detecting mouthwash allergic reactions associated with ROEM. Case Presentation: A 29-year-old woman came to the Oral Medicine clinic complaining of canker sores all over her mouth and swollen lips accompanied by crusts that had been bleeding easily two months prior. Complaints worsened after the patient used alcohol-containing mouthwash without a history of fever or other symptoms. Extra-oral examination showed upper and lower lip edema with hemorrhagic crusts that bleed easily. No lesions were found in other parts of the body. Intra-oral examination showed ulcers, multiple, irregular in almost the entire oral mucosa. Laboratory examination revealed non-reactive anti-HSV-1 IgG and a total IgE serum level of 612.00 IU/mL. The diagnosis based on the examination results is recurrent oral erythema multiforme. Case Management: The patient was instructed to stop using alcohol-containing mouthwash, maintain oral hygiene, a healthy lifestyle, adequate hydration, and a balanced diet. Prednisone, benzydamine HCL mouthwash, 0.025% hyaluronic acid mouthwash, multivitamins, and hydrocortisone cream were given as pharmacological therapy. The oral lesions improved in 12 days and the total IgE serum level examination showed a decrease (385 IU/mL). Conclusion: The total IgE examination can be a screening tool for mouthwash allergy-related reactions to disease and represents the response of ROEM therapy as evidenced by clinical improvement. [ABSTRACT FROM AUTHOR]

Cannabis allergy is a relatively new phenomenon described in the 1970s. Its increased frequency has been observed over the last years due to the increasing therapeutic and recreational use of cannabis-based products. Sensitization possibly leading to allergy symptoms can occur not only through the smoking of cannabis, but also through ingestion, the inhalation of pollen, or direct contact. The severity of symptoms varies from benign pruritus to anaphylaxis. There is scant information available to support clinicians throughout the entire therapeutic process, starting from diagnosis and ending in treatment. In this review, we present six cases of patients in whom molecular in vitro testing revealed sensitization to cannabis extract and/or cannabis-derived nsLTP molecules (Can s 3). Based on these cases, we raise important questions regarding this topic. The article discusses current proposals and highlights the importance of further research not only on cannabis allergy but also on asymptomatic sensitization to cannabis allergens, which may be ascertained in some percentage of the population. [ABSTRACT FROM AUTHOR]

Identification and characterization of allergens associated with helminth infestations is important. These allergens belong to common allergens and have different biological functions. The activity of some allergens associated with helminth infestations has been studied and it has been determined that during helminth infestations, various substances are produced in the host's body, and some of them stimulate the synthesis of specific IgE, and a few of them cause allergic reactions. The activity of allergens associated with helminth infestations (the ability to induce IgEmediated inflammation) has been studied clinically and experimentally. In several epidemiological studies, it has been established that IgE response to helminths is a risk factor for asthma and atopy (i.e. susceptibility to allergies). Revision of existing diagnostic methods and standards of allergic processes in helminthiasis, and research on molecular mechanisms of metabolism of allergens related to helminth infestations should be continued. [ABSTRACT FROM AUTHOR]

Gluten hypersensitivity is characterized by the production of IgE antibodies against specific wheat proteins (allergens) and a myriad of clinical allergic symptoms including life-threatening anaphylaxis. Currently, the only recommended treatment for gluten hypersensitivity is the complete avoidance of gluten. There have been extensive efforts to develop dietary-based novel therapeutics for combating this disorder. There were four objectives for this study: (i) to compile the current understanding of the mechanism of gluten hypersensitivity; (ii) to critically evaluate the outcome from preclinical testing of novel therapeutics in animal models; (iii) to determine the potential of novel dietary-based therapeutic approaches under development in humans; and (iv) to synthesize the outcomes from these studies and identify the gaps in research to inform future translational research. We used Google Scholar and PubMed databases with appropriate keywords to retrieve published papers. All material was thoroughly checked to obtain the relevant data to address the objectives. Our findings collectively demonstrate that there are at least five promising dietary-based therapeutic approaches for mitigating gluten hypersensitivity in development. Of these, two have advanced to a limited human clinical trial, and the others are at the preclinical testing level. Further translational research is expected to offer novel dietary-based therapeutic options for patients with gluten hypersensitivity in the future. [ABSTRACT FROM AUTHOR]

Objective: Transient receptor potential (TRP) channels are crucial for the response of many different mediators, including histamine and substance P. Currently, it is not clear whether stimulation of TRP channels alter the degranulation thresholds of skin mast cells. Thus, this proof of concept study aimed to test whether mast cell-driven wheal and erythema responses are modified by short-term stimulation of TRP channels with capsaicin. Materials and Methods: Skin prick testing was applied with histamine and grass pollen extract in sensitized individuals, as a model to explore the possible effects of capsaicin on IgE-mediated itch, wheal, and flare development. Results: We showed that short-term TRP stimulation by topical capsaicin treatment resulted with a significant difference in maximum wheal diameter (12.5±3.7 mm vs. 7.9±3.4 mm, p=0.02), average wheal area (76.4±31.0 mm² vs 35.3±17.4 mm², p=0.01), maximum erythema diameter (38.5±13.9 mm vs. 28.8±14.5 mm, p=0.07) and average erythema area (973±709 mm² vs 556±499 mm² ; p=0.02) between capsaicin-pretreated areas compared to placebo-pretreated areas. No differences in itch, wheal and erythema responses between capsaicin-pretreated and placebo-pretreated areas were observed after skin prick testing with histamine. Conclusion: This study showed that short-term TRP stimulation increases IgE-mediated but not histamine-induced wheal and erythema responses. [ABSTRACT FROM AUTHOR]

Wheat allergy dependent on augmentation factors (WALDA) is the most common gluten allergy in adults. IgE-mediated sensitizations are directed towards ω5-gliadin but also to other wheat allergens. The value of the different in vitro cellular tests, namely the basophil activation test (BAT) and the active (aBHRA) and passive basophil histamine-release assays (pBHRA), in the detection of sensitization profiles beyond ω5-gliadin has not been compared. Therefore, 13 patients with challenge-confirmed, ω5-gliadin-positive WALDA and 11 healthy controls were enrolled. Specific IgE (sIgE), skin prick tests, BATs, aBHRA, and pBHRA were performed with allergen test solutions derived from wheat and other cereals, and results were analyzed and compared. This study reveals a distinct and highly individual reactivity of ω5-gliadin-positive WALDA patients to a range of wheat allergens beyond ω5-gliadin in cellular in vitro tests and SPT. In the BAT, for all tested allergens (gluten, high-molecular-weight glutenin subunits, α-amylase/trypsin inhibitors (ATIs), alcohol-free wheat beer, hydrolyzed wheat proteins (HWPs), rye gluten and secalins), basophil activation in patients was significantly higher than in controls (p = 0.004–p < 0.001). Similarly, significant histamine release was detected in the aBHRA for all test substances, exceeding the cut-off of 10 ng/mL in all tested allergens in 50% of patients. The dependency of tests on sIgE levels against ω5-gliadin differed; in the pBHRA, histamine release to any test substances could only be detected in patients with sIgE against ω5-gliadin ≥ 7.7 kU/L, whereas aBHRA also showed high reactivity in less sensitized patients. In most patients, reactivity to HWPs, ATIs, and rye allergens was observed. Additionally, alcohol-free wheat beer was first described as a promising test substance in ω5-gliadin-positive WALDA. Thus, BAT and aBHRA are valuable tools for the identification of sensitization profiles in WALDA. [ABSTRACT FROM AUTHOR]

A study published in the journal Allergy explores the relationship between IgE-mediated allergies and Alzheimer's disease (AD). The study found that patients with clinical symptoms of IgE-mediated allergy had a higher risk of developing AD compared to those without allergies. The researchers detected AD biomarkers in the cerebrospinal fluid of patients with allergies, suggesting a potential link between allergic inflammation and neuroinflammation. However, the study's findings were limited by the small sample size, and further research is needed to fully understand the role of allergic inflammation in AD development. [Extracted from the article]

The basis of our current understanding of allergies begins with the discovery of IgE in the mid-1960s. The whole theory of the physiology and pathophysiology of allergic diseases, including rhinitis and asthma, dates from that period. Among the key regions of IgE identified were the FAB (fragment antigen binding) portion that has the ability to capture allergens, and the Cε3 domain, through which IgE binds to its membrane receptor. It was then postulated that blocking IgE at the level of the Cε3 domain would prevent it from binding to its receptor and thus set in motion the allergic cascade. This was the beginning of the development of omalizumab, a monoclonal antibody with an anti-IgE effect. In this article, we review the pathophysiology of allergic disease and trace the clinical development of omalizumab. We also review the benefits of omalizumab treatment that are apparently unrelated to allergies, such as its effect on immunity and bronchial remodeling. [ABSTRACT FROM AUTHOR]

Background: Helminths are potent immunomodulators and in their chronic infection state they may protect against allergy‐related disease and atopy. However, they are also known for inducing allergic conditions. This study aimed to assess the association between helminths, atopy and allergic conditions. Methods: A total of 461 school children participated in this cross‐sectional study. Data on allergic symptoms and a range of confounding variables was gathered from parents via an interviewer‐led questionnaire. Skin sensitization to house dust mite and cockroaches was analyzed, and a stool sample was collected for helminth analysis. Serum total Immunoglobulin E using enzyme‐linked immunosorbent assay and eosinophil count were also measured. Results: Overall sensitivity to both allergens was 2.4%. Self‐reported allergic outcomes in the last 12 months for the 461 participants had been : wheezing 3.7%, asthma 2.2%, eczema 13.2% and hay fever 6.9%. Overall, the prevalence of helminth infection was 11.9% (53/444). A borderline significant association was found between atopy and any allergy symptoms (odds ratio [OR]: 3.32, 95% confidence interval [95% CI: 0.99, 11.1], p =.052). There was no significant association between helminths and atopy (OR: 0.64 [95% CI: 0.29, 1.41], p =.268) and also between helminths and allergic symptoms (OR: 0.64 [95% CI: 0.29, 1.41], p =.268). Bivariate analysis showed keeping an animal in the house increases the risk of atopy while maternal and paternal history of allergy increases the risk of developing allergic symptoms in the children. Conclusion and clinical relevance: This study found a non‐significant inverse association between helminths infection and atopy and allergic disorders, likely due to reduced statistical power, resulting in a lower prevalence of atopy and allergic conditions. A high powered longtitudinal study is necessary to explore the casuality and potential therapeutic benefits of helminths for allergic disorders. [ABSTRACT FROM AUTHOR]

Allergic diseases in children are major public health concerns due to their widespread and rising prevalence. Food-specific immunoglobulin G4(FS-IgG4) has been detected in patients with allergic diseases, but its clinical significance is still debated. In the present study, 407 children with allergic diseases were recruited and categorized into three groups according to the different systems involved: the respiratory system group, the skin system group, and a multiple system group, with the collection of clinical symptoms and serum antibodies, including total immunoglobulin E (IgE), house dust mite (HDM) IgE, food-specific IgE (FS-IgE), and FS-IgG4. Part of these patients were followed up with the intervention of FS-IgG4-guided diet elimination with or without add-on probiotics supplement. The analysis at baseline revealed distinct serum levels of different antibodies. The positive rate of FS-IgG4 in all groups was more than 80%, and the proportion of total IgE and FS-IgG4 both positive in the multisystem group was the highest (p=0.039). Egg and milk were the foods with the highest positive rate of FS-IgG4 in all groups. After diet elimination for more than 3 months, serum FS-IgG4 in children significantly decreased (P<0.05) along with the improvement of clinical symptoms, regardless of the add-on of probiotics. However, the intervention did not impact the serum levels of total IgE, FS-IgE, and HDM IgE. There was no further decrease of serum FS-IgG4 level in children followed up for more than 1 year, which may be related to noncompliance with diet elimination. Multivariate regression analysis revealed that the decline of serum FS-IgG4 was an independent predictable factor for the improvement of clinical symptoms (adjusted OR:1.412,95%CI 1.017–1.96, p=0.039). The add-on of probiotics showed less efficiency in reducing the FS-IgG4 level in more patients with relief of clinical symptoms. Our results confirmed the correlation between FS-IgG4 and allergic diseases, and the decreased FS-IgG4 could be a useful predictor for the improvement of allergic symptoms. FS-IgG4-guided diet elimination is an efficient treatment for allergic diseases. Our study adds solid data to the clinical significance of FS-IgG4 in allergic diseases. [ABSTRACT FROM AUTHOR]

Chronic urticaria (CU) is one of the most common dermatological diseases and has a significant impact on the quality of life of patients. However, the pathogenesis of this disease remains unclear. Autoimmunity in chronic spontaneous urticaria (CSU) has received considerable attention and has been studied previously. Atopy is an important characteristic of CU; however, it has not been fully recognized. Atopy predisposes individuals to immune responses to allergens, leading to type 2 inflammation and immunoglobulin E (IgE) overproduction. Compared with healthy individuals, patients with CU have a higher proportion of atopy, and an atopic background is correlated with the clinical characteristics of CU. The total IgE levels in patients with CU is significantly higher than those in healthy individuals. Although its level is not higher than that in classic allergic diseases, it is closely related to CU. Exogenous allergens, auto-allergens, and specific IgEs, which are closely related to atopy, have been reported, and their roles in CU pathogenesis are also being studied. Local and systemic atopic inflammation is present in patients with CU. This review summarizes the current knowledge regarding atopy and CU, speculating that there are CU subtypes, such as atopic CSU or atopic chronic inducible urticaria (CIndU) and that atopy may be involved in the pathogenesis of CU. These findings provide a new perspective for a comprehensive understanding of the clinical features of CU and further research regarding its pathogenesis. [ABSTRACT FROM AUTHOR]

The rising global incidence of IgE-mediated allergic reactions poses a significant challenge to the quality of life of affected individuals and to healthcare systems, with current treatments being limited in effectiveness, safety, and disease-modifying capabilities. IgE acts by sensitizing the highaffinity IgE receptor FcεRI expressed by mast cells and basophils, tuning these cells for inflammatory degranulation in response to future allergen encounters. In recent years, IgG has emerged as an essential negative regulator of IgE-dependent allergic inflammation. Mechanistically, studies have proposed different pathways by which IgG can interfere with the activation of IgE-mediated inflammation. Here, we briefly summarize the major proposed mechanisms of action by which IgG controls the IgE-FceRI inflammatory axis and how those mechanisms are currently applied as therapeutic interventions for IgE-mediated inflammation. [ABSTRACT FROM AUTHOR]

Background: Severe asthma (SA) in horses, resembling human asthma, is a prevalent, debilitating allergic respiratory condition marked by elevated allergen‐specific immunoglobulin E (IgE) against environmental proteins; however, research exploring the exposome's influence on IgE profiles is currently limited but holds paramount significance for diagnostic and therapeutic developments. Animals: Thirty‐five sports horses were analyzed, consisting of environmentally matched samples from France (5 SA; 6 control), the United States (6 SA; 6 control), and Canada (6 SEA; 6 control). Methods: This intentional cross‐sectional study investigated the sensitization profiles of SA‐affected and healthy horses via serological antigen microarray profiling. Partial least square‐discriminant analysis (PLS‐DA) was used to identify and rank the importance of allergens for class separation (ie, affected/non‐affected) as variable influence of projection (VIP), and allergen with commonality internationally established via frequency analysis. Results: PLS‐DA models showed high discriminatory power in predicting SA in horses from Canada (area under the curve [AUC] 0.995) and France (AUC 0.867) but poor discriminatory power in horses from the United States (AUC 0.38). Hev b 5.0101, Cyn D, Der p 2, and Rum cr were the only shared allergens across all geographical groups. Conclusions and Clinical Importance: Microarray profiling can identify specific allergenic components associated with SA in horses, while mathematical modeling of this data can be used for disease classification, highlighting the variability of sensitization profiles between geographical locations and emphasizing the importance of local exposure to the prevalence of different allergens. Frequency scoring analysis can identify important variables that contribute to the classification of SA across different geographical regions. [ABSTRACT FROM AUTHOR]

This article discusses the efficacy of skin care interventions in preventing eczema and food allergy in infants. The study found that emollients, such as moisturizers, during infancy do not significantly impact the risk of developing eczema. However, they may increase the chance of developing mild local skin infections. The study also highlights a lack of trials studying other approaches to infant skincare for preventing eczema. Further research is needed to understand whether different approaches to infant skin care might prevent eczema or food allergy. [Extracted from the article]

Simple Summary: It has long been known that antibodies of a certain class, called IgE, are the main cause of allergic reactions to food. Other antibody types such as IgA and IgG can suppress the allergic reaction. Even IgE, which binds the allergen only weakly (i.e., with low affinity), seems to have a protective effect. This review discusses the role of distinct antibody types in food allergy, and the underlying mechanisms of action. These findings might be important to understand the development and course of food allergies, and could help to improve diagnostics and therapy. 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. [ABSTRACT FROM AUTHOR]

The current study was conducted to measure some immunoglobulin IgE, IgG, IgM, some interleukins interleukin 4 (IL-4), interleukin 5 (IL-5) and a complete blood count (CBC) in patients suffering from hypersensitivity type 1 (drug allergy, and asthma). The study began from 1/9/2022 to 1/3/2023 and included 59 people of all ages. The current results showed that people with drug allergy and asthma had an increase in the concentration of IL-4 (407.8 ±27.0), (837.6 ± 29.4), IL-5 (323.1 ±39.7) (568.4 ± 32.1) respectively. The level of IgE, IgG and IgM was elevated in patients suffering from drug allergies (11.2±2.6) (18.1±2.8) (and 47.9±5.3) respectively and asthma was (30.3±3.4), (26.1 ± 4.6) and (50.2 ± 8.6) respectively. The results of the complete blood count showed a significant increase in the white blood cells, Eosinphile. In addition to many differences in blood parameters compared to normal proportions. It was also found that the IgE concentration decreased with age, while the IgG antibody concentration increased compared to the standard sample and with the increase in age groups. [ABSTRACT FROM AUTHOR]

Fruit allergies manifest with a diverse array of clinical presentations, ranging from localized contact allergies and oral allergy syndrome to the potential for severe systemic reactions including anaphylaxis. The scope of population-level prevalence studies remains limited, largely derived from single-center or hospital-based investigations. In this comprehensive review, we conducted a systematic literature search spanning the years 2009 to 2023, with full acknowledgment of potential analytical biases, to provide a global overview of fruit allergy prevalence. The primary mechanistic underpinning of fruit allergies stems from cross-reactivity between aeroallergens and food allergens, a consequence of structurally similar epitopes—a phenomenon recognized as pollen food allergy syndrome (PFAS). In the era of molecular allergology, numerous studies have dissected allergen components with substantial clinical relevance. Within this review, we explore important allergenic molecules found in plant-based foods, scrutinize pertinent cross-reactivity patterns, and offer insights into management recommendations. Additionally, we compare guideline recommendations to enhance clinical understanding and inform decision making. [ABSTRACT FROM AUTHOR]

This article discusses a study conducted in Sweden that aimed to investigate the association between the gut microbiome and allergic asthma in a cohort of twin children aged 9 to 14. The study found no evidence of differences in the overall gut microbial richness or composition between healthy controls and children diagnosed with allergic asthma, asthma only, or IgE sensitization only. The combined activity of raised IgE and asthma on the differential abundance in allergic asthma was almost exclusively additive, with no systematic evidence for synergistic or antagonistic effects. The study provides valuable insights into the role of the gut microbiome in asthma and contributes to the understanding of allergic diseases. [Extracted from the article]

Food-dependent exercise-induced allergic reactions (FDEIA) represent a distinct clinical phenomenon where symptoms arise during exercise following the consumption of specific trigger foods, with the most severe manifestation being anaphylaxis—a condition distinct from typical exercise-induced or food-induced anaphylaxis. In FDEIA, patients can either exercise or tolerate specific foods separately without experiencing any allergic reactions. Diagnosis relies on patient history and provocation testing, requiring rigorous implementation within a supervised hospital environment. Positive symptoms and clinical signs during testing confirm FDEIA, while negative outcomes do not preclude its presence. Exercise stands as the primary trigger, followed by nonsteroidal anti-inflammatory drugs (NSAIDs) and alcohol. The utilization of various protocols for food cofactor challenges to confirm FDEIA yields differing diagnostic outcomes. We highlight the updated concept of food cofactor challenges, incorporating protocols reported in the literature, and summarize current recommendations and comprehensive management approaches for FDEIA patients. [ABSTRACT FROM AUTHOR]

Background: Grass leaf has been suspected of causing immunoglobulin (Ig)E‐mediated immediate hypersensitivity reactions in humans and dogs. However, most studies in this area are case‐control studies without in vitro data showing the involvement of IgE in the reaction. Laboratory studies have demonstrated the reactivity to a 50–55 kDa protein with clinical signs immediately after contact with grass leaf material. The clinical findings of dogs with atopic‐like dermatitis immediately after contact with grass leaf material suggest the involvement of grass leaves as the allergen source. Objectives: This study was designed to test the IgE‐reactivity of grass leaf proteins in dogs with clinical signs and positive scratch test results against grass leaf material. Materials and Methods: The serum of 41 patients with a history of allergy and suspected to grass leaf material was immunoblotted against grass leaf extracts from five suspected grass species. The IgE‐positive blots were separated with 2D gel electrophoresis and analysed with mass spectrometry (MS). Commercially supplied proteins were used to validate immunoblot activity. Results: The serum of 25 dogs diagnosed with grass dermatitis had positive IgE‐specific immunoblot against one or more grass leaf extracts. The MS data indicated a reactive band at 55 kDa to be beta‐amylase or RuBisCO (ribulose‐1,5‐bisphosphate carboxylase/oxygenase) large subunit (RbLS). All tested dog sera showed IgE‐reactivity with beta‐amylase and some with RbLS. Conclusions and Clinical Relevance: Canines with clinical signs of grass‐related dermatitis had IgE‐reactivity against grass leaf proteins. Serum IgE‐reactivity to beta‐amylase and RuBisCO large subunit may indicate that these proteins act as allergens, possibly causing pruritus and skin lesions. [ABSTRACT FROM AUTHOR]

Poorly controlled asthma is especially common in low resource countries. Aside from lack of access to, or poor technique with, inhaled beta-2 agonists and corticosteroids, the most problematic forms of asthma are frequently associated with both fungal allergy and exposure, especially in adults leading to more asthma exacerbations and worse asthma. The umbrella term 'fungal asthma' describes many disorders linked to fungal exposure and/or allergy to fungi. One fungal asthma endotype, ABPA, is usually marked by a very high IgE and its differential diagnosis is reviewed. Both ABPA and fungal bronchitis in bronchiectasis are marked by thick excess airway mucus production. Dermatophyte skin infection can worsen asthma and eradication of the skin infection improves asthma. Exposure to fungi in the workplace, home and schools, often in damp or water-damaged buildings worsens asthma, and remediation improves symptom control and reduces exacerbations. Antifungal therapy is beneficial for fungal asthma as demonstrated in nine of 13 randomised controlled studies, reducing symptoms, corticosteroid need and exacerbations while improving lung function. Other useful therapies include azithromycin and some biologics approved for the treatment of severe asthma. If all individuals with poorly controlled and severe asthma could be 'relieved' of their fungal allergy and infection through antifungal therapy without systemic corticosteroids, the health benefits would be enormous and relatively inexpensive, improving the long term health of over 20 million adults and many children. Antifungal therapy carries some toxicity, drug interactions and triazole resistance risks, and data are incomplete. Here we summarise what is known and what remains uncertain about this complex topic. [ABSTRACT FROM AUTHOR]

Recurrent aphthous stomatitis is one of the most common ulcerative disorders associated with oral mucosa. The etiology of recurrent aphthous stomatitis remains unclear and is considered idiopathic. Several plausible triggers have been studied as predisposing to recurrent aphthous stomatitis, where one of the predisposing factors is allergy. This study aimed to determine the relationship between recurrent aphthous stomatitis and allergy through a history of allergy and IgE levels. The study involved 50 recurrent aphthous stomatitis patients. The inclusion criteria included patients with minor type recurrent aphthous stomatitis, who do not have a systemic disease or take any drug, do not use orthodontic appliances, and are voluntarily willing to be the study subject. Recurrent aphthous stomatitis is diagnosed with anamnesis to determine the recurrence of recurrent aphthous stomatitis and history of allergy and clinical examination to examine the ulcer of recurrent aphthous stomatitis. After that, patients had blood samples taken for IgE levels. The data obtained were then analyzed for the relationship between allergy history and IgE with chi-square. Patients with a history of allergy mainly had a high value of IgE with 12 (85,7%). There was a significant relationship between the history of allergy and IgE levels of recurrent aphthous stomatitis patients with a p-value of 0.013 (p<0.05). It can be concluded that it is crucial to examine the history of allergy and perform laboratory examinations to search for predisposing factors in recurrent aphthous stomatitis patients. [ABSTRACT FROM AUTHOR]

Allergy is a life-threatening, acute disease mainly caused by mediators released from immunoglobulin E and allergen-activated mast cells. Syk, an intracellular signaling molecule important for cancer development, was supposed to have a critical role in mast cell activation. Thus, we clarified the anti-allergic effect of potent Syk inhibitor entospletinib in vivo mouse allergic model and in vitro cell cultures. Immunoglobulin E and allergen-mediated degranulation of rat basophilic leukemia RBL2H3 cells was suppressed by quite low concentrations of entospletinib (10 nM or more) occurring in 20 min without affecting cell viability. The drug treatment (3 nM or more) also inhibited cytokine secretion from the immunoglobulin E and allergen-activated RBL2H3 cells within 4 h. Rectal temperature decrease caused by passive systemic anaphylaxis in mice was diminished obviously by oral administration of a small amount of entospletinib (0.3 mg/mouse). Increase of the concentration of mouse mast cell protease-1, an indicator of mast cell activation, in serum of mice upon the passive systemic anaphylaxis induction was also attenuated by the oral administration of entospletinib, similar to its inhibitory effect on RBL2H3 activation observed in vitro. These findings indicated that Syk inhibitor entospletinib inhibited allergic reaction via blunting mast cell activation. Syk inhibitor entospletinib and its derivatives might be good candidates as anti-allergic drugs. [ABSTRACT FROM AUTHOR]

Following a diagnosis of IgE‐mediated food allergy, to secure the best outcome, the patient should receive individualized advice tailored to their specific needs, which considers the type and presentation of the food involved, level of exclusion required, risk of cross‐contamination and any variance required for age, ethnicity, financial issues, and lifestyle. Issues such as food labels "may contain" statements, and variation in the threshold of reaction and impact of cofactors should also be considered. Most important is the need to ensure that the diagnosis is robust, especially given the nutritional, psychological, and socioeconomic issues that can affect an individual with a diagnosis of food allergy. Unnecessary exclusion of one or more foods that have not triggered allergic reactions, especially in individuals with allergic comorbidities, can result in severe IgE‐mediated reactions on re‐exposure. Given that food allergies may change over time, the diagnosis should be reviewed, to determine whether resolution is likely, or new‐food triggers are reported. Regular assessment is vital, especially during childhood, to ensure reintroduction occurs at an appropriate time, thus enabling increased diversity of the diet and improvement in the quality of life. For some, an IgE‐mediated food allergy may necessitate the life‐long exclusion of foods, and for others, a food habitually eaten suddenly triggers an allergic reaction in adult life. People of all ages, ethnicities, and socioeconomic backgrounds deserve individual advice on the management of their food allergy to support a healthy diet and improve quality of life. [ABSTRACT FROM AUTHOR]

This review evaluates the current modes of allergen-specific immunotherapy for cockroach allergens, in terms of clinical outcomes and explores future trends in the research and development needed for a more targeted cockroach immunotherapy approach with the best efficacy and minimum adverse effects. Cockroach allergy is an important risk factor for allergic rhinitis in the tropics, that disproportionately affects children and young adults and those living in poor socio-economic environments. Immunotherapy would provide long-lasting improvement in quality of life, with reduced medication intake. However, the present treatment regime is long and has a risk of adverse effects. In addition, cockroach does not seem to have an immuno-dominant allergen, that has been traditionally used to treat allergies from other sources. Future trends of cockroach immunotherapy involve precision diagnosis, to correctly identify the offending allergen. Next, precision immunotherapy with standardized allergens, which have been processed in a way that maintains an immunological response without allergic reactions. This approach can be coupled with modern adjuvants and delivery systems that promote a Th1/Treg environment, thereby modulating the immune response away from the allergenic response. • Immunotherapy is an appealing long-term solution for treating cockroach allergies as they are difficult to eliminate. • Using recombinant allergens for allergen immunotherapy improves the reproducibility of treatment outcomes. • Cockroach allergens can be made even safer for immunotherapy by removing its IgE-epitopes while retaining antigenicity. • Immunotherapy based on cross-reacting allergen groups should be considered for certain allergens. • Accurate patient selection via precision allergen testing is the first step towards precision AIT. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that vitamin D has a protective effect on allergic diseases, while an individual's sex may have a moderating effect on the relationship between vitamin D and allergic‐related immunity. This study aimed to determine the role of vitamin D in children with coexisting allergic diseases in the context of sex differences and to explore the behavioral profiles of these patients. We recruited a total of 103 children with atopic diseases and divided them into four groups: males with one allergic disease (MA1, n = 20), males with two or more allergic diseases (MA2, n = 26), females with one allergic disease (FA1, n = 30), and females with two or more allergic diseases (FA2, n = 27). We measured serum calcium levels using the colorimetric method and serum 25‐OH vitamin D total levels using electrochemiluminescence immunoassay. We found that MA2 had significantly lower vitamin D levels than MA1 and FA2. The levels of IgE were negatively correlated with vitamin D in females, whereas the levels of IgE were not significantly correlated with vitamin D in males. Furthermore, serum IgE was significantly correlated with children's adaptive skills, and different sexes were associated with different aspects of adaptive skills. Our findings suggest a protective role of vitamin D in the development of one allergic disease against the coexistence of allergic diseases in males, as well as extend the evidence for sex differences in immunity by demonstrating a sex‐different correlation between IgE and vitamin D and the relationship between IgE and children's adaptive skills. [ABSTRACT FROM AUTHOR]

Anaphylaxis is a life-threatening or even fatal systemic hypersensitivity reaction. The incidence of anaphylaxis has risen at an alarming rate in the past decades in the majority of countries. Generally, the most common causes of severe or fatal anaphylaxis are medication, foods and Hymenoptera venoms. Anaphylactic reactions are characterized by the activation of mast cells and basophils and the release of mediators. These cells express a variety of receptors that enable them to respond to a wide range of stimulants. Most studies of anaphylaxis focus on IgE-dependent reactions. The mast cell has long been regarded as the main effector cell involved in IgE-mediated anaphylaxis. This paper reviews IgE-independent anaphylaxis, with special emphasis on mast cells, basophils, anaphylactic mediators, risk factors, triggers, and management. [ABSTRACT FROM AUTHOR]

Drug hypersensitivity reactions are a serious concern in clinical practice because they can be severe and result in lifelong sequelae. An accurate diagnosis and identification of the culprit drug is essential to prevent future reactions as well as for the identification of safe treatment alternatives. Nonetheless, the diagnosis can be challenging. In vivo and in vitro tests can be helpful, although none are conclusive; therefore, the tests are not usually performed in isolation but as part of a diagnostic algorithm. In addition, some in vitro tests are only available in research laboratories, and standardization has not been fully accomplished. Collaborating research is needed to improve drug hypersensitivity reaction diagnosis. In this review, we update the current available in vivo and in vitro tools with their pros and cons and propose an algorithm to integrate them into clinical practice. [ABSTRACT FROM AUTHOR]

• Shrimp is among the most common food allergen that causes severe allergic reactions, however, there is still a lack of experimental models for the study of shrimp allergy and prophylactic approaches development. • Subcutaneous sensitization induced a Th2-driven cytokine response at draining lymph nodes. • Oral exposure to shrimp antigens induced high titters of serum and intestinal mucosal anti-shrimp antibodies. • Eosinophils are found in the lamina propria of the jejunum of allergic mice. • Allergic mice show histological morphometric changes as a shortage of intestinal villi length and crypt depth. Shrimp is among the most sensitizing food allergens and has been associated with many anaphylaxis reactions. However, there is still a shortage of studies that enable a systematic understanding of this disease and the investigation of new therapeutic approaches. This study aimed to develop a new experimental model of shrimp allergy that could enable the evaluation of new prophylactic treatments. BALB/c mice were subcutaneously sensitized with 100 μg of shrimp proteins of Litopenaeus vannamei adsorbed in 1 mg of aluminum hydroxide on day 0, and a booster (100 µg of shrimp proteins only) on day 14. The oral challenge protocol was based on the addition of 5 mg/ml of shrimp proteins to water from day 21 to day 35. Analysis of shrimp extract content detected at least 4 of the major allergens reported to L. vannamei. In response to the sensitization, allergic mice showed significantly enhanced IL-4 and IL-10 production in restimulated cervical draining lymph node cells. High detection of serum anti-shrimp IgE and IgG1 suggested the development of allergies to shrimp while Passive Cutaneous Anaphylaxis assay revealed an IgE-mediated response. Immunoblotting analysis revealed that Allergic mice developed antibodies to multiple antigens present in the shrimp extract. These observations were supported by the detection of anti-shrimp IgA production in intestinal lavage samples and morphometric intestinal mucosal changes. Therefore, this experimental protocol can be a tool to evaluate prophylactic and therapeutic approaches. [ABSTRACT FROM AUTHOR]

The significance of B‐cell memory in sustaining IgE‐mediated allergies but also ensuring the development of long‐term allergen tolerance has remained enigmatic. However, well‐thought murine and human studies have begun to shed more light on this highly disputed subject. The present mini review highlights important aspects, like the involvement of IgG1 memory B cells, the meaning of low‐ or high‐affinity IgE antibody production, the impact of allergen immunotherapy, or the relevance of local memory established by ectopic lymphoid structures. Based on recent findings, future investigations should lead to deeper knowledge and the development of improved therapies treating allergic individuals. [ABSTRACT FROM AUTHOR]

Simple Summary: Anaphylaxis is the most severe form of allergic reactions and can be life-threatening. It is very difficult to study the mechanisms underlying anaphylaxis in humans since these events are rare and often lethal. Therefore, animal models have been established. Mice and rats are mostly used since their biological parameters, such as temperature drop, behavioral changes, and blood or cell biomarkers, can be easily measured in the laboratory. These animals can also be genetically modified to express human proteins and cell functions. Different animal models have been established to replicate as closely as possible the natural route of sensitization to the allergen and to trigger anaphylaxis in animals. These animal models have deepened our knowledge on human anaphylaxis with certain limitations, as discussed in this review. Allergies and atopy have emerged as significant public health concerns, with a progressively increasing incidence over the last two decades. Anaphylaxis is the most severe form of allergic reactions, characterized by a rapid onset and potentially fatal outcome, even in healthy individuals. Due to the unpredictable nature and potential lethality of anaphylaxis and the wide range of allergens involved, clinical studies in human patients have proven to be challenging. Diagnosis is further complicated by the lack of reliable laboratory biomarkers to confirm clinical suspicion. Thus, animal models have been developed to replicate human anaphylaxis and explore its pathophysiology. Whereas results obtained from animal models may not always be directly translatable to humans, they serve as a foundation for understanding the underlying mechanisms. Animal models are an essential tool for investigating new biomarkers that could be incorporated into the allergy workup for patients, as well as for the development of novel treatments. Two primary pathways have been described in animals and humans: classic, predominantly involving IgE and histamine, and alternative, reliant on IgG and the platelet-activating factor. This review will focus essentially on the former and aims to describe the most utilized IgE-mediated anaphylaxis animal models, including their respective advantages and limitations. [ABSTRACT FROM AUTHOR]

Backgrounds: Interleukin 4 (IL 4) is a cytokine associated with the cause of several allergic diseases such as asthma due to their function in the differentiation of T helper type 2 lymphocytes and induction of the IgE isotype switch. Object: The study aims to determine the association IL-4 level with total serum IgE levels and asthma severity. Methods: A cross-section study was performed. Eighty-seven subjects were recruited from Karbala Teaching Hospital for Children in the period extending from January 25 to May 24, 2022, including children with asthma, were subjected to measure IL 4 level using Elabscience ELISA kit and measured total IgE level using AccuBind IgE ELISA kit. Results: Eighty-seven subjects of asthmatic children in which the mean age was 7.833 ± 3.652. There are 65.52% and 34.48% of asthmatic children (male and female, respectively). Total serum IgE was 398.889 ± 227.156 IU/ml, while the IL-4 level was 5.18 ± 8.224. There was a significant difference in IL 4 levels depending on asthma severity (P= 0.037). IL-4 levels in severe persistent asthma were higher than IL-4 levels in mild and moderate persistent asthma. Further, there was a highly significant difference in IL 4 levels depending on asthma controlled (P= 0.004). IL-4 levels in not well-controlled asthma were higher than IL-4 levels in well and partial controlled asthma. In addition, there was no significant correlation between IL-4 levels and total serum IgE levels (P=0.436). Conclusion: IL 4 has an important role in predicting asthma severity and asthma control in children. These findings have important implications for the treatment of IgE-mediated asthma. Despite this, IL 4 levels have no significant correlation with total serum IgE levels. [ABSTRACT FROM AUTHOR]

Background: BALB/c and C57BL/6 mouse strains are commonly used in allergy research. The current study investigated the immunological differences between these two mouse strains with a locally allergic rhinitis model. Methods: Eighteen BALB/c and eighteen C57BL/6 mice received different doses of ovalbumin (OVA) intranasally for eight weeks (each mouse strain has three subgroups, 25 mg/mL group, 0.25 mg/mL group, and the PBS group). The allergic symptoms, OVA-specific serum antibody (IgE, IgG1, IgG2a), cytokines (IL-4, IFN-γ, IL-10) in the splenic culture supernatant, infiltrating eosinophils and goblet cells in local nasal mucosa were measured. RNA-seq technology was applied to detect differential gene expression in the local nasal mucosa. Results: With the same dose of OVA stimulation, the exacerbation of allergic symptoms was more pronounced in C57BL/6 than in BALB/c. BALB/c serum IgE, IgG1, and IgG2a gradually increased, and C57BL/6 produced fewer serum antibodies IgE and IgG1, while IgG2a never increased. BALB/c spleen cell culture supernatant IL-4 and IL-10 increased with increasing dose, and IFN-γ increased significantly in the intermediate dose group, while IL-4, IL-10, and IFN-γ did not increase in C57BL/6. The infiltration of eosinophils and goblet cells in both mice was proportional to the dose, while C57BL/6 was elevated more than BALB/c. RNA-seq suggested that the innate immune response, immune system process function, Jun kinase (JNK) pathway, and MAPKK pathway were upregulated in C57BL/6 compared to BALB/c. The core genes responsible for the differential immune response in both mice with allergic rhinitis were Kng2, Kng1, Gnb3, Lpar3, Lpar1, Pik3r1, Pf4, Apob, Rps9, and Fbxo2. Conclusion: There are significant differences in the immunologic responses between BALB/c mice and C57BL/6 mice. BALB/c mice developed mild local allergic inflammatory reactions and strong systemic immune responses. In contrast, C57BL/6 mice had stronger local allergic inflammatory responses and relatively mild systemic immune responses. Different mice strains can be selected according to the research purpose. [ABSTRACT FROM AUTHOR]

The mechanism for anaphylaxis following mRNA COVID-19 vaccination has been widely debated; understanding this serious adverse event is important for future vaccines of similar design. A mechanism proposed is type I hypersensitivity (i.e., IgE-mediated mast cell degranulation) to polyethylene glycol (PEG). Using an assay that, uniquely, had been previously assessed in patients with anaphylaxis to PEG, our objective was to compare anti-PEG IgE in serum from mRNA COVID-19 vaccine anaphylaxis case-patients and persons vaccinated without allergic reactions. Secondarily, we compared anti-PEG IgG and IgM to assess alternative mechanisms. Selected anaphylaxis case-patients reported to U.S. Vaccine Adverse Event Reporting System December 14, 2020–March 25, 2021 were invited to provide a serum sample. mRNA COVID-19 vaccine study participants with residual serum and no allergic reaction post-vaccination ("controls") were frequency matched to cases 3:1 on vaccine and dose number, sex and 10-year age category. Anti-PEG IgE was measured using a dual cytometric bead assay (DCBA). Anti-PEG IgG and IgM were measured using two different assays: DCBA and a PEGylated-polystyrene bead assay. Laboratorians were blinded to case/control status. All 20 case-patients were women; 17 had anaphylaxis after dose 1, 3 after dose 2. Thirteen (65 %) were hospitalized and 7 (35 %) were intubated. Time from vaccination to serum collection was longer for case-patients vs controls (post-dose 1: median 105 vs 21 days). Among Moderna recipients, anti-PEG IgE was detected in 1 of 10 (10 %) case-patients vs 8 of 30 (27 %) controls (p = 0.40); among Pfizer-BioNTech recipients, it was detected in 0 of 10 case-patients (0 %) vs 1 of 30 (3 %) controls (p >n 0.99). Anti-PEG IgE quantitative signals followed this same pattern. Neither anti-PEG IgG nor IgM was associated with case status with both assay formats. Our results support that anti-PEG IgE is not a predominant mechanism for anaphylaxis post-mRNA COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Mites are among the major sources of domestic and occupational allergens worldwide, and continuous exposure to these allergens leads to chronic airway inflammation. One of the most allergenic species is the storage mite Tyrophagus putrescentiae (Schrank). Protein extracts are produced from this mite for tests that help the clinical diagnosis (via prick test), treatment, and monitoring of disease progression in patients who had positive results for allergic reactions. Therefore, the aim of the present study was to evaluate the cell viability of RAW 264.7 and L929 cells when exposed to in-house raw protein extracts of T. putrescentiae compared to a commercial product, as well as quantify TNF-α secretion by RAW 264.7. Additionally, this study quantified the effect of these extracts in IgE secretion in total blood of people affected by this mite. The study found similarity between the in-house extract and the commercial extract as they had equivalent TNF-α secretion. Additionally, viabilities of RAW 264.7 and L929 exposed to the in-house extract were compatible with viabilities of cells exposed to the commercial extract, with no cytotoxicity at the concentrations tested. Results corroborated the hypothesis that the extract produced in-house would be equivalent to the commercial extract in allergic patients when the IgE was quantified. This study is the first to show the cytotoxicity of T. putrescentiae extracts, and to provide a quantitative analysis of TNF-α and IgE. [ABSTRACT FROM AUTHOR]

Background: House dust mite (HDM) is the most common airborne source causing complex allergy symptoms. There are geographic differences in the allergen molecule sensitization profiles. Serological testing with allergen components may provide more clues for diagnosis and clinical management. Objective: This study aims to investigate the sensitization profile of eight HDM allergen components in a large number of patients enrolled in the clinic and to analyze the relation of gender, age, and clinical symptoms in North China. Methods: The 548 serum samples of HDM-allergic patients (ImmunoCAP® d1 or d2 IgE ≥0.35) were collected in Beijing City and divided in four different age groups and three allergic symptoms. The specific IgE of HDM allergenic components, Der p 1/Der f 1, Der p 2/Der f 2, Der p 7, Der p 10, Der p 21, and Der p 23, was measured using the micro-arrayed allergen test kit developed by Hangzhou Zheda Dixun Biological Gene Engineering Co., Ltd. The new system was validated by comparing to single-component Der p 1, Der p 2, and Der p 23 tests by ImmunoCAP in 39 sera. The epidemiological study of these IgE profiles and the relation to age and clinical phenotypes were analyzed. Results: A greater proportion of male patients was in the younger age groups, while more female patients were in the adult groups. Both the sIgE levels and the positive rates (approximately 60%) against Der p 1/Der f 1 and Der p 2/Der f 2 were higher than for the Der p 7, Der p 10, and Der p 21 components (below 25%). The Der f 1 and Der p 2 positive rates were higher in 2–12-year-old children. The Der p 2 and Der f 2 IgE levels and positive rates were higher in the allergic rhinitis group. The positive rates of Der p 10 increased significantly with age. Der p 21 is relevant in allergic dermatitis symptom, while Der p 23 contributes to asthma development. Conclusion: HDM groups 1 and 2 were the major sensitizing allergens, with group 2 being the most important component relevant to respiratory symptoms in North China. The Der p 10 sensitization tends to increase with age. Der p 21 and Der p 23 might be associated with the development of allergic skin disease and asthma, respectively. Multiple allergen sensitizations increased the risk of allergic asthma. [ABSTRACT FROM AUTHOR]

Background: Allergic diseases are triggered by signaling through the high‐affinity IgE receptor, FcεRI. In both mast cells (MCs) and basophils, FcεRI is a tetrameric receptor complex comprising a ligand‐binding α subunit (FcεRIα), a tetraspan β subunit (FcεRIβ, MS4A2) responsible for trafficking and signal amplification, and a signal transducing dimer of single transmembrane γ subunits (FcεRIγ). However, FcεRI also exists as presumed trimeric complexes that lack FcεRIβ and are expressed on several cell types outside the MC and basophil lineages. Despite known differences between humans and mice in the presence of the trimeric FcεRI complex, questions remain as to how it traffics and whether it signals in the absence of FcεRIβ. We have previously reported that targeting FcεRIβ with exon‐skipping oligonucleotides eliminates IgE‐mediated degranulation in mouse MCs, but equivalent targeting in human MCs was not effective at reducing degranulation. Results: Here, we report that the FcεRIβ‐like protein MS4A6A exists in human MCs and compensates for FcεRIβ in FcεRI trafficking and signaling. Human MS4A6A promotes surface expression of FcεRI complexes and facilitates degranulation. MS4A6A and FcεRIβ are encoded by highly related genes within the MS4A gene family that cluster within the human gene loci 11q12‐q13, a region linked to allergy and asthma susceptibility. Conclusions: Our data suggest the presence of either FcεRIβ or MS4A6A is sufficient for degranulation, indicating that MS4A6A could be an elusive FcεRIβ‐like protein in human MCs that performs compensatory functions in allergic disease. [ABSTRACT FROM AUTHOR]

Background: Peanut allergy accounts for the majority of food‐induced hypersensitivity reactions and can lead to lethal anaphylaxis. Animal models can provide an insight into the immune mechanisms responsible for sensitization and allergic anaphylaxis. However, different mouse strains and sensitization protocols can influence the successful development of a peanut allergic mouse model. Objective: We aimed at developing a systemic anaphylaxis model of peanut allergy that resembles human anaphylaxis. We compared the immunological and clinical responses in genetically different mouse strains. Methods: Female BALB/c, C57BL/6, and C3H mice were intraperitoneally sensitized and later challenged with peanut proteins. Allergen‐specific serology was done by ELISA, and anaphylaxis was evaluated by monitoring changes in body temperature upon systemic challenge. Results: Sensitization to peanut was successful in C3H mice and triggered production of allergen‐specific antibodies, cytokines and anaphylaxis. Allergic reactions were characterized by the release of allergic mediators and by changes in leukocyte populations in blood and in the peritoneal cavity. Among the identified major peanut allergens, Ara h 2 showed the strongest anaphylactic potential. Much lower or no trigger of peanut‐specific antibodies was observed in BALB/c and C57BL/6 mice, which experienced no hypersensitivity reactions. Conclusions: Mouse strain matters for testing of peanut protein allergens. We identified C3H mice as a suitable strain for the development of a mouse model of peanut‐allergic anaphylaxis. Pre‐clinical, humoural and cellular responses resembled the responses observed in human patients. The described model can be useful for further studies on peanut allergy and for the development of new therapeutic strategies. [ABSTRACT FROM AUTHOR]