Alpha-gal syndrome: when treatment of hypovolemic shock can lead to anaphylaxis.

Delayed anaphylaxis after ingestion of red meat because of galactose-alpha-1,3-galactose (alpha-gal) syndrome has increased in recent years. The mechanism involves an immunoglobulin E reaction to alpha-gal, a molecule found in mammalian meat, dairy products, medications and excipients containing mammalian-derived components, and tick salivary glycans. Sensitization occurs due to the bite of a lone star tick and the transmission of alpha-gal molecules into person's bloodstream. We describe a case of alpha-gal syndrome with severe food, drug, and perioperative allergy in which anaphylaxis with hypovolemic shock occurred immediately after an emergency surgical procedure, when a gelatin-containing drug was injected. This case study confirms that the clinical manifestations of alpha-gal syndrome could be different depending on the route of administration, with immediate reactions if an alpha-gal-containing drug is injected and delayed type allergic manifestations occurring several hours after oral intake. The purpose of this report is to highlight the importance of risk communication in case of exposure to medical products and surgical procedures of patients with alpha-gal syndrome and to encourage drug manufacturers to indicate clearly the origin of excipients in product literature.

Role of serum-specific immunoglobulin E in egg allergy: a comprehensive study of Portuguese pediatric patients.

INTRODUCTION: Food allergies represent a growing public health concern, particularly among children. This study aims to examine egg allergy in pediatric patients and analyze the value of serum-specific immunoglobulin E (sIgE) levels as predictive biomarkers for oral food challenge (OFC) outcomes. METHODS: Retrospective study, involving pediatric patients with suspected IgE-mediated egg allergy, conducted at a tertiary hospital. RESULTS: Data from 176 pediatric patients were analyzed, revealing a higher male prevalence (59.1%). Most cases (40.3%) presented symptoms in the first year of life, predominantly mucocutaneous symptoms (46%). OFC results varied across various forms of egg presentation, with cooked egg being the most frequently tested food. Positive OFCs were observed in 14.6% (n = 36) of cases. The study identified specific egg protein biomarkers for positive OFC, with ovalbumin for raw egg (sIgE > 1.28 KUA/L; area under the curve [AUC] = 0.917; sensitivity [S] 100%; and specificity [Sp] 92%), ovomucoid for cooked egg (sIgE > 0.99 KUA/L; AUC = 0.788, 95%; S: 79%; and Sp: 74%), and ovomucoid for baked egg (sIgE> 4.63 KUA/L; AUC = 0.870; S: 80%; and Sp: 85%) showing predictive capacities. CONCLUSIONS: The findings underscore the importance of considering various forms of egg presentation in the diagnosis and management of egg allergy. The findings highlight the valuable discriminatory capacity and provided reliable biomarkers, such as ovalbumin for raw egg and ovomucoid for cooked and baked egg in risk assessment, aiding in predicting OFC outcomes and helping clinicians to make informed decisions in diagnosing and managing egg allergies, thus improving patient care and quality of life.

Atopic Dermatitis: Pathophysiology.

The pathophysiology of atopic dermatitis is complex and multifactorial, involving elements of barrier dysfunction, alterations in cell-mediated immune responses, IgE-mediated hypersensitivity, and environmental factors. Loss-of-function mutations in filaggrin have been implicated in severe atopic dermatitis due to a potential increase in trans-epidermal water loss, pH alterations, and dehydration. Other genetic changes have also been identified, which may alter the skin's barrier function, resulting in an atopic dermatitis phenotype. The imbalance of Th2 to Th1 cytokines observed in atopic dermatitis can create alterations in the cell-mediated immune responses and can promote IgE-mediated hypersensitivity, both of which appear to play a role in the development of atopic dermatitis. One must additionally take into consideration the role of the environment on the causation of atopic dermatitis and the impact of chemicals such as airborne formaldehyde, harsh detergents, fragrances, and preservatives. Use of harsh alkaline detergents in skin care products may also unfavorably alter the skin's pH causing downstream changes in enzyme activity and triggering inflammation. Environmental pollutants can trigger responses from both the innate and adaptive immune pathways. This chapter will discuss the multifaceted etiology of atopic dermatitis, which will help us to elucidate potential therapeutic targets. We will also review existing treatment options and their interaction with the complex inflammatory and molecular triggers of atopic dermatitis.

Current options in the management of tree nut allergy: A systematic review and narrative synthesis.

Tree nut allergy is a lifelong and potentially life-threatening condition. The standard of care is strictly avoiding the culprit nut and treating accidental reactions symptomatically. To evaluate potential therapeutic options for desensitizing patients with IgE-mediated tree nut allergy, we systematically searched three bibliographic databases for studies published until January 2024. We looked for active treatments of IgE-mediated allergy to tree nuts (walnut, hazelnut, pistachio, cashew, almond, pecan, macadamia nut, and brazil nut). We focused on allergen-specific immunotherapy (AIT) using oral (OIT), sublingual (SLIT), epicutaneous (EPIT), or subcutaneous (SCIT) delivery, or other disease-modifying treatments. We found 19 studies that met our criteria: 3 studies investigated sublingual immunotherapy, 5 studied oral immunotherapy to a single tree nut, and 6 used multi-food oral immunotherapy with or without omalizumab. The remaining studies investigated the effectiveness of monoclonal antibodies or IgE-immunoadsorption in multi-food allergic patients, including patients with tree nut allergy. The heterogeneity of the studies prevented pooling and meta-analysis. Oral immunotherapy, single or multi-nut, with or without omalizumab, was the most studied approach and appears effective in conferring protection from accidental exposures. Omalizumab monotherapy is the only approved alternative management for reducing allergic reactions that may occur with accidental exposure.

T-cell receptor diversity and allergen sensitivity in childhood asthma and atopic dermatitis.

BACKGROUND: Childhood allergies of asthma and atopic dermatitis (AD) involve an overactive T-cell immune response triggered by allergens. However, the impact of T-cell receptor (TCR) repertoires on allergen sensitization and their role in mediating different phenotypes of asthma and AD in early childhood remains unclear. METHODS: A total of 78 children, comprising 26 with asthma alone, 26 with AD alone, and 26 healthy controls (HC), were enrolled. TCR repertoire profiles were determined using a unique molecular identifier system for next-generation sequencing. Integrative analyses of their associations with allergen-specific IgE levels and allergies were performed. RESULTS: The diversity in TCR alpha variable region (TRAV) genes of TCR repertoires and complementarity determining region 3 (CDR3) clonality in TRAV/TRBV (beta) genes were significantly higher in children with AD compared with those with asthma and HC (p < .05). Compared with HC, the expression of TRAV13-1 and TRAV4 genes was significantly higher in both asthma and AD (p < .05), with a significant positive correlation with mite-specific IgE levels (p < .01). In contrast, TRBV7-9 gene expression was significantly lower in both asthma and AD (p < .01), with this gene showing a significant negative correlation with mite-specific IgE levels (p < .01). Furthermore, significantly higher TRAV8-3 gene expression, positively correlated with food-specific IgE levels, was found in children with AD compared with those with asthma (p < .05). CONCLUSION: Integrated TCR repertoires analysis provides clinical insights into the diverse TCR genes linked to antigen specificity, offering potential for precision immunotherapy in childhood allergies.

[Recent advances in the practical management of allergic rhinitis.] / Recenti progressi nella gestione pratica della rinite allergica.

Allergic rhinitis (AR) is a widespread disease, and its prevalence is still growing. AR may be associated with other diseases, including conjunctivitis, rhinosinusitis, asthma, food allergy, and atopic dermatitis. Diagnosis is based on history, physical examination, documentation of sensitization, such as the production of allergen-specific IgE, also using molecular diagnostics in selected patients. Treatments is based on education, engagement, allergen avoidance, non-pharmacological and pharmacological remedies, and allergen-specific immunotherapy (Ait). Symptomatic treatments mainly concern intranasal/oral antihistamines and/or nasal corticosteroids. This article also aims to discuss new management strategies for AR patients. The self-management of allergic rhinitis could include new strategies. In this regard, particular interest should be considered to intranasal corticosteroids and antihistamines without medical prescription, probiotics and other natural substances, and new formulations (tablets) of Ait.

Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma.

Background: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials. Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life. Methods: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers. Results: Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and <0.001, respectively); however, this prediction was not improved by the addition of IgE. Conclusions: The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.

Trimeric Bet v 1-specific nanobodies cause strong suppression of IgE binding.

Background: Around 20% of the population in Northern and Central Europe is affected by birch pollen allergy, with the major birch pollen allergen Bet v 1 as the main elicitor of allergic reactions. Together with its cross-reactive allergens from related trees and foods, Bet v 1 causes an impaired quality of life. Hence, new treatment strategies were elaborated, demonstrating the effectiveness of blocking IgG antibodies on Bet v 1-induced IgE-mediated reactions. A recent study provided evidence for the first time that Bet v 1-specific nanobodies reduce patients´ IgE binding to Bet v 1. In order to increase the potential to outcompete IgE recognition of Bet v 1 and to foster cross-reactivity and cross-protection, we developed Bet v 1-specific nanobody trimers and evaluated their capacity to suppress polyclonal IgE binding to corresponding allergens and allergen-induced basophil degranulation. Methods: Nanobody trimers were engineered by adding isoleucine zippers, thus enabling trimeric formation. Trimers were analyzed for their cross-reactivity, binding kinetics to Bet v 1, and related allergens, and patients' IgE inhibition potential. Finally, their efficacy to prevent basophil degranulation was investigated. Results: Trimers showed enhanced recognition of cross-reactive allergens and increased efficiency to reduce IgE-allergen binding compared to nanobody monomers. Furthermore, trimers displayed slow dissociation rates from allergens and suppressed allergen-induced mediator release. Conclusion: We generated high-affine nanobody trimers that target Bet v 1 and related allergens. Trimers blocked IgE-allergen interaction by competing with IgE for allergen binding. They inhibited IgE-mediated release of biological mediators, demonstrating a promising potential to prevent allergic reactions caused by Bet v 1 and relatives.

Seminal plasma hypersensitivity: A systematic review of clinical presentation, diagnostics, and management options.

INTRODUCTION: Seminal plasma hypersensitivity (SPH) is a rare and often misdiagnosed condition characterized by local and/or systemic reactions to seminal plasma proteins following exposure to semen. We aimed to summarize key symptomatology, diagnostic features, and management options for SPH. METHODS: The databases PubMed, EMBASE, Web of Science, Google Scholar, and Cochrane Review were searched with key words "seminal plasma hypersensitivity" and "seminal fluid allergy" through September 2023. Exclusion criteria included non-English articles, in vitro studies, publication before 1990, duplicates, and articles with no clinical relevance to SPH in women. RESULTS: The search yielded 53 articles for review. Of these, 60.5% described systemic SPH and 39.5% described localized. CONCLUSION: Diagnosis of SPH relies on a thorough patient history and confirmatory skin prick testing. The use of IgE assays is controversial and less accurate for cases of localized SPH. Knowledge of disease immunopathology, systemic versus localized symptom presentation, patient preference, and desire to conceive should guide management options. Artificial insemination has the potential for severe adverse reactions in systemic SPH so necessitates extra procedural precautions. SPH does not appear to impair fertility. Additional research on specific allergens implicated in SPH can aid in the development of more targeted immunotherapy approaches with improved safety and efficacy.

Animal-derived food allergen: A review on the available crystal structure and new insights into structural epitope.

Immunoglobulin E (IgE)-mediated food allergy is a rapidly growing public health problem. The interaction between allergens and IgE is at the core of the allergic response. One of the best ways to understand this interaction is through structural characterization. This review focuses on animal-derived food allergens, overviews allergen structures determined by X-ray crystallography, presents an update on IgE conformational epitopes, and explores the structural features of these epitopes. The structural determinants of allergenicity and cross-reactivity are also discussed. Animal-derived food allergens are classified into limited protein families according to structural features, with the calcium-binding protein and actin-binding protein families dominating. Progress in epitope characterization has provided useful information on the structural properties of the IgE recognition region. The data reveals that epitopes are located in relatively protruding areas with negative surface electrostatic potential. Ligand binding and disulfide bonds are two intrinsic characteristics that influence protein structure and impact allergenicity. Shared structures, local motifs, and shared epitopes are factors that lead to cross-reactivity. The structural properties of epitope regions and structural determinants of allergenicity and cross-reactivity may provide directions for the prevention, diagnosis, and treatment of food allergies. Experimentally determined structure, especially that of antigen-antibody complexes, remains limited, and the identification of epitopes continues to be a bottleneck in the study of animal-derived food allergens. A combination of traditional immunological techniques and emerging bioinformatics technology will revolutionize how protein interactions are characterized.

Structural and Immunological Features of PR-10 Allergens: Focusing on the Major Alder Pollen Allergen Aln g 1.

Today, allergies have become a serious problem. PR-10 proteins are clinically relevant allergens that have the ability to bind hydrophobic ligands, which can significantly increase their allergenicity potential. It has been recently shown that not only the birch pollen allergen Bet v 1 but also the alder pollen allergen Aln g 1, might act as a true sensitizer of the immune system. The current investigation is aimed at the further study of the allergenic and structural features of Aln g 1. By using qPCR, we showed that Aln g 1 was able to upregulate alarmins in epithelial cells, playing an important role in sensitization. With the use of CD-spectroscopy and ELISA assays with the sera of allergic patients, we demonstrated that Aln g 1 did not completely restore its structure after thermal denaturation, which led to a decrease in its IgE-binding capacity. Using site-directed mutagenesis, we revealed that the replacement of two residues (Asp27 and Leu30) in the structure of Aln g 1 led to a decrease in its ability to bind to both IgE from sera of allergic patients and lipid ligands. The obtained data open a prospect for the development of hypoallergenic variants of the major alder allergen Aln g 1 for allergen-specific immunotherapy.

Gut Microbiome-Serum Metabolism Revealed the Allergenicity of Ferulic Acid Combined with Glucose-Modified ß-Lactoglobulin.

A novel strategy combining ferulic acid and glucose was proposed to reduce ß-lactoglobulin (BLG) allergenicity and investigate whether the reduction in allergenicity was associated with gut microbiome and serum metabolism. As a result, the multistructure of BLG changed, and the modified BLG decreased significantly the contents of IgE, IgG, IgG1, and mMCP-1 in serum, improved the diversity and structural composition of gut microbiota, and increased the content of short-chain fatty acids (SCFAs) in allergic mice. Meanwhile, allergic mice induced by BLG affected arachidonic acid, tryptophan, and other metabolic pathways in serum, the modified BLG inhibited the production of metabolites in arachidonic acid metabolism pathway and significantly increased tryptophan metabolites, and this contribution helps in reducing BLG allergenicity. Overall, reduced allergenicity of BLG after ferulic acid was combined with glucose modification by regulating gut microbiota, the metabolic pathways of arachidonic acid and tryptophan. The results may offer new thoughts alleviating the allergy risk of allergenic proteins.

Association of serum total IgE and allergen-specific IgE with insulin resistance in adolescents: an analysis of the NHANES database.

BACKGROUND: Recent studies have found that total immunoglobulin E (IgE) and allergen-specific IgE were associated with some metabolic diseases. However, the role of IgE in metabolism among adolescents is still unclear. Herein, this study aims to investigate the associations of serum total IgE and allergen-specific IgE with insulin resistance (IR) in adolescents, in order to provide some reference for the prevention and treatment of metabolic diseases in a young age. METHODS: Data of 870 adolescents were extracted from the National Health and Nutrition Examination Survey (NHANES) database in 2005-2006 in this cross-sectional study. Weighted univariate and multivariate logistic regression analyses were utilized to screen covariates and explore the relationships of serum total IgE and allergen-specific IgE with IR. The evaluation indexes were odds ratios (ORs) and 95% confidence intervals (CIs). In addition, these relationships were also assessed in subgroups of allergy history, asthma history, and number of allergens. RESULTS: Among eligible adolescents, 168 had IR. No significant association between serum total IgE level and IR was found. However, adolescents with higher level of allergen-specific IgE to rye grass [OR = 0.47, 95%CI: (0.25-0.91)], white oak [OR = 0.57, 95%CI: (0.37-0.88)], or peanut [OR = 0.38, 95%CI: (0.15-0.97)] seemed to have lower odds of IR, whereas those had higher level of shrimp-specific IgE [OR = 2.65, 95%CI: (1.21-5.84)] have increased odds of IR. In addition, these associations between allergen-specific IgE and IR were also discovered in adolescents who had allergy history or asthma history, or had different numbers of allergens. CONCLUSION: Paying attention to different allergens in adolescents may be important in the early identification of IR among this high-risk population. The study results relatively provided some reference for further exploration on IR prevention.

Structure-based epitope prediction and assessment of cross-reactivity of Myrmecia pilosula venom-specific IgE and recombinant Sol g proteins (Solenopsis geminata).

The global distribution of tropical fire ants (Solenopsis geminata) raises concerns about anaphylaxis and serious medical issues in numerous countries. This investigation focused on the cross-reactivity of allergen-specific IgE antibodies between S. geminata and Myrmecia pilosula (Jack Jumper ant) venom proteins due to the potential emergence of cross-reactive allergies in the future. Antibody epitope analysis unveiled one predominant conformational epitope on Sol g 1.1 (PI score of 0.989), followed by Sol g 2.2, Sol g 4.1, and Sol g 3.1. Additionally, Pilosulin 1 showed high allergenic potential (PI score of 0.94), with Pilosulin 5a (PI score of 0.797) leading in B-cell epitopes. The sequence analysis indicated that Sol g 2.2 and Sol g 4.1 pose a high risk of cross-reactivity with Pilosulins 4.1a and 5a. Furthermore, the cross-reactivity of recombinant Sol g proteins with M. pilosula-specific IgE antibodies from 41 patients revealed high cross-reactivity for r-Sol g 3.1 (58.53%) and r-Sol g 4.1 (43.90%), followed by r-Sol g 2.2 (26.82%), and r-Sol g 1.1 (9.75%). Therefore, this study demonstrates cross-reactivity (85.36%) between S. geminata and M. pilosula, highlighting the allergenic risk. Understanding these reactions is vital for the prevention of severe allergic reactions, especially in individuals with pre-existing Jumper Jack ant allergy, informing future management strategies.

Novel IgE crosslinking-induced luciferase expression method using human-rat chimeric IgE receptor-carrying mast cells.

BACKGROUND: The measurement of antigen-specific serum IgE is common in clinical assessments of type I allergies. However, the interaction between antigens and IgE won't invariably trigger mast cell activation. We previously developed the IgE crosslinking-induced luciferase expression (EXiLE) method using the RS-ATL8 mast cell line; however, the method may not be sensitive enough in some cases. METHODS: In this study, we introduced an NF-AT-regulated luciferase reporter gene into the RBL-2H3 rat mast cell line and expressed a chimeric high-affinity IgE receptor (FcεRI) α chain gene, comprising an extracellular domain from humans and transmembrane/intracellular domains from rats. RESULTS: We generated multiple clones expressing the chimeric receptor. Based on their responsiveness and proliferation, we selected the HuRa-40 clone. This cell line exhibited significantly elevated human α chain expression compared to RS-ATL8 cells, demonstrating a 10-fold enhancement of antigen-specific reactivity. Reproducibility across different batches and operators was excellent. Moreover, we observed a detectable response inhibition by an anti-allergy drugs (omalizumab and cyclosporin A). CONCLUSIONS: HuRa-40 cells-which carry the human-rat chimeric IgE receptor-comprise a valuable reporter cell line for the EXiLE method. Their versatility extends to various applications and facilitates high-throughput screening of anti-allergy drugs.

Short-time ozone treatment promotes protease-mediated destruction of B cell allergen epitopes by altering the structural characteristics of whey protein.

A novel processing method combining short-time ozone pretreatment with hydrolysis has been developed to reduce whey protein allergenicity. The results showed that ozone treatment altered the whey protein spatial structure, initially increasing the surface hydrophobicity index, and then decreasing due to polymer formation as the time increased. Under the optimized conditions of alkaline protease-mediated hydrolysis, a 10-second pre-exposure to ozone significantly promoted the reduction in the IgE binding capacity of whey protein without compromising the hydrolysis efficiency. Compared with whey protein, the degranulation of KU812 cells stimulated by this hydrolysate decreased by 20.54%, 17.99%, and 22.80% for IL-6, ß-hexosaminidase, and histamine, respectively. In vitro simulated gastrointestinal digestion confirmed increased digestibility and reduced allergenicity. Peptidomics identification revealed that short-time ozonation exposed allergen epitopes, allowing alkaline protease to target these epitopes more effectively, particularly those associated with α-lactalbumin. These findings suggest the promising application of this processing method in mitigating the allergenicity of whey protein.

Basophil allergen threshold sensitivity to casein (casein-specific CD-sens) predicts allergic reactions at a milk challenge in most but not all patients.

BACKGROUND: The basophil activation test is an emerging clinical tool in the diagnosis of cow's milk allergy (CMA). The aim was to assess the association between the basophil allergen threshold sensitivity to the major milk protein casein (casein-specific CD-sens), the levels of milk- and casein-specific Immunoglobulin E antibodies (IgE-ab), and the severity of allergic reactions at milk challenges. METHODS: We enrolled 34 patients aged 5-15 (median 9) years who underwent a double-blind placebo-controlled milk-challenge (DBPCMC) as screening before inclusion in an oral immunotherapy study for CMA. The severity of the allergic reaction at the DBPCMC was graded using Sampson's severity score. Venous blood was drawn before the DBPCMC. Milk- and casein-specific IgE-ab were analyzed. Following in vitro stimulation of basophils with casein, casein-specific CD-sens, was determined. RESULTS: Thirty-three patients completed the DBPCMC. There were strong correlations between casein-specific CD-sens and IgE-ab to milk (rs = 0.682, p < .001), and between casein-specific CD-sens and IgE-ab to casein (rs = 0.823, p < .001). There was a correlation between the severity of the allergic reaction and casein-specific CD-sens level (rs = 0.395, p = .041) and an inverse correlation between casein-specific CD-sens level and the cumulative dose of milk protein to which the patient reacted at the DBPCMC (rs = -0.418, p = .027). Among the 30 patients with an allergic reaction at the DBPCMC, 67% had positive casein-specific CD-sens, 23% had negative casein-specific CD-sens, and 10% were declared non-responders. CONCLUSION: Two thirds of those reacting at the DBPMC had positive casein-specific CD-sens, but reactions also occurred despite negative casein-specific CD-sens. The association between casein-specific CD-sens and the severity of the allergic reaction and cumulative dose of milk protein, respectively, was moderate.

Breast milk-mediated exposure to dioxins and antigen in infancy enhances antigen-specific antibody production capacity in adulthood in mice.

The immune system is sensitive to many chemicals. Among dioxin compounds, 2,3,7,8-tetrachlorodizenzo-p-dioxin (TCDD) is the most toxic environmental pollutant. The effects of perinatal maternal exposure to dioxins may persist into childhood. However, there have been no reports to date on the effects of exposure to dioxins during infancy, when the immune organs are developing. Therefore, we investigated the effects of TCDD and antigen exposure during lactation on immune function, especially antibody production capacity, in adult mice. Beginning the day after delivery, lactating mothers were orally administered TCDD or a mixture of TCDD and ovalbumin (OVA) daily for 4 weeks, until the pups were weaned. At 6 weeks of age, progeny mice were orally administered OVA daily for 10 weeks, while non-progeny mice were orally administered OVA or a mixture of TCDD and OVA daily for 10 weeks. Production of serum OVA-specific IgG was examined weekly. The amount of TCDD transferred from the mother to the progeny via breast milk was determined by measuring TCDD in the gastric contents of the progeny. A trend toward increasing IgA titer was observed in TCDD-treated mice, and production of IgE was observed only in progeny whose mothers were treated with TCDD and OVA. The results suggest that exposure to TCDD and OVA in breast milk can affect immune function in newborns.

[Mast Cell-Neutrophil Communication Regulates Allergic Diseases].

Allergic diseases (e.g., food allergies) are a growing problem, with increasing numbers of individuals experiencing them worldwide. Congruently, the adverse reactions (e.g., anaphylaxis) associated with the administration of vaccines against emerging infectious diseases such as coronavirus disease 2019 (COVID-19) have become a familiar problem. Allergic diseases, which have a wide variety of symptoms, are difficult to prevent or cure; treatment is currently limited to therapeutic drugs or allergen immunotherapy. Therefore, elucidating new allergic regulatory factors that control the allergic (i.e., mast cell) responses is important. While investigating the regulatory mechanisms of the wide range of allergic responses of mast cells, we found that the affinity of allergens to immunoglobin E (IgE) regulates allergic inflammation through the differences in the secretory responses of mast cells and the types and interactions of the cells infiltrating the tissues. Here, we present our recent findings regarding the affinity of allergens to IgE in regulating allergic inflammation, heterogeneous secretory granules inducing diverse secretory responses, and mast cells interacting with neutrophils, thereby regulating the various allergic responses.

Allergen skin test responses in broad U.S. asthma population in those with and without rhinitis.

Background: Asthma and allergic rhinitis are pathologically interlinked conditions. Despite skin testing (ST) being pivotal for evaluating allergic sensitization, U.S. data that date back to 1960s on ST reactivity patterns in subjects with asthma remain sparse. Objective: The purpose of this study was to elucidate seasonal, perennial ST responses, and their relationship with asthma severity, early versus late onset disease, and immunoglobulin E (IgE) levels. Methods: Five hundred patients with asthma were randomly selected from the National Jewish Health electronic medical record over a 3-year span. Demographic, clinical, and allergen ST reactivity data for a battery of seasonal and perennial allergens were procured, including total IgE levels, asthma onset, and severity, by using t-tests, χ² tests, and Analysis of Variance (ANOVA), patterns of reactivity were assessed for overall, seasonal, and perennial allergens in relation to IgE levels, asthma onset, and severity. Results: Of the 500 patients, 398 were analyzed. 63.3% were women, 50.1% had adult-onset asthma, and 86.1% had rhinitis; 75.3% tested positive to one or more allergens, with men demonstrating higher overall (p = 0.039) and perennial (p = 0.035) sensitization. ST reactivity varied based on the presence of rhinitis for seasonal (p = 0.028) but not perennial (p = 0.733) allergens. Asthma severity was not significantly associated with ST reactivity (p > 0.10). ST positivity for perennial (p < 0.001) but not seasonal (p = 0.128) allergens was higher in childhood-onset asthma versus adult-onset asthma despite both groups having a large percentage of reactors. Elevated IgE levels correlated with ST reactivity (p < 0.01). Conclusion: Our study represents a unique comprehensive evaluation of ST reactivity in a U.S. asthma population, which is lacking in the literature, when factoring in asthma onset, severity, and IgE levels. Our findings underscore the importance of allergen sensitization in asthma, regardless of severity, concurrent rhinitis symptoms, or asthma onset, which challenge some of the prevailing assumptions about the relationship between allergen sensitization and asthma onset.