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The article in Clinical & Experimental Allergy explores the connection between lymphopenia, basopenia, and eosinopenia in chronic spontaneous urticaria (CSU) patients, particularly those with autoimmune CSU. The study involved 300 CSU patients and found that lymphopenia was associated with lower counts of basophils, eosinophils, monocytes, and platelets. The research suggests that lymphopenia may reflect the migration of lymphocytes from the bloodstream into skin lesions, similar to basophils and eosinophils. The study also identified associations between basopenia and high anti-C1q levels, supporting the hypothesis that these antibodies may be a marker of autoimmune CSU. [Extracted from the article]

A study published in the Clinical & Experimental Allergy journal found that low levels of vitamin D in early childhood were associated with aeroallergen-specific IgE in children with a history of severe bronchiolitis. However, there was no association between vitamin D levels and total, food-specific, or outdoor-aeroallergen-specific IgE. The study suggests that vitamin D plays a role in immune modulation and may be involved in allergic diseases. The study had limitations, such as a small sample size and not accounting for geographic factors and individual allergen exposure. Further research is needed to fully understand the relationship between vitamin D and allergic sensitization. [Extracted from the article]

Background: Studying the sensitisation profiles of patients with allergies allows for a deeper understanding of the disease which may facilitate the selection of the best‐personalised allergen immunotherapy. This observational, cross‐sectional, multicentre study aimed to demonstrate the heterogeneity of the German population with allergies by analysing specific immunoglobulin E (sIgE) patterns towards aeroallergens and exploring the relationship between sensitisation and clinical symptoms. Methods: In total, 500 patients with allergies from different regions of Germany were recruited based on their case histories, clinical allergic symptoms and skin prick test data for aeroallergens. Serum samples were analysed using ImmunoCAP assays to determine sIgE levels for 33 allergenic sources and 43 molecular allergens. Results: Most patients (81%) were polysensitised. Betula verrucosa pollen was the most common cause of sensitisation (59%), followed by Phleum pratense (58%) and Dermatophagoides pteronyssinus (44%). The highest prevalence rates of molecular allergens were observed for Bet v 1 (84%) from birch pollen, Phl p 1 from grass pollen (82%), Der p 2 (69%) from mites and Fel d 1 (69%) from cat. Polysensitisation was significantly associated with the presence of asthma and the severity of rhinitis symptoms. Conclusions: Our findings show a high rate of polysensitisation and emphasise the importance of molecular diagnosis for more precise and comprehensive insights into sensitisation patterns and their association with clinical symptoms. These data may help improve personalised diagnosis and immunotherapy adapted to the needs of individual patients in the region. [ABSTRACT FROM AUTHOR]

This research letter discusses the protein content of commercially available early introduction products for infants and emphasizes the importance of early introduction of allergenic foods in preventing food allergies. The authors express concerns about the safety and quality of some early introduction products, including discrepancies in protein content. The document also references three studies related to allergic reactions in infants and the prevention of food allergies, providing valuable insights into the prevention and management of food allergies in infants. [Extracted from the article]

The article discusses recent initiatives aimed at harmonizing outcomes in food allergy clinical trials and observational research. The initiatives, COFAITH and COMFA, identified common outcomes such as desensitization, sustained unresponsiveness/remission, quality of life, and allergic symptoms. COFAITH focused on immunotherapy trials, while COMFA sought consensus on core outcomes for all food allergy interventions. The article emphasizes the importance of considering patient preferences and cultural influences on food consumption when determining outcomes for clinical trials. It also highlights the need for collaboration between clinicians, researchers, industry, and patient representatives to improve the lives of those managing food allergies. [Extracted from the article]

This article examines the timing of sensitization to hen's eggs and nuts in infants with eczema. The study found that the age of sensitization onset differed between egg white and tree nuts, with sensitization to nuts occurring at older ages. The rate of sensitization to nuts was notably lower than that to egg whites. The study suggests that introducing nuts by 6 months of age may be a safe strategy to reduce the incidence of food allergy. However, the study also acknowledges the challenges of introducing nuts due to their texture during the initial phases of weaning. The authors plan to conduct further research to explore the preventive effects of walnut allergy based on the timing of walnut consumption initiation. [Extracted from the article]

Introduction: Allergen‐specific IgE‐blocking IgG antibodies contribute to successful allergen immunotherapy (AIT), however, not much is known about their affinity. Since affinity measurements of polyclonal antibodies in serum are technically challenging we evaluated the applicability of acidic disruption of antibody‐allergen complexes by a modified ELISA protocol with monoclonal antibodies (mAbs) specific for the relevant major allergens Betv1 and Mald1. Then, AIT‐induced blocking and non‐blocking Mald1‐specific antibodies in sera from individuals with or without reduced apple allergy were compared. Methods: After testing their pH stability coated recombinant allergens were incubated with (i) mAbs diluted in PBS or human serum and (ii) sera from individuals after sublingual administration of Mald1 or Betv1 for 16 weeks. Immune complexes were exposed to buffers in the pH range of 6.4–3.4 and residual antibodies were measured. Avidity indexes (AI), defined as the pH removing 50% of antibodies, were compared to the dissociation constants (KD) of mAbs determined by surface plasmon resonance. Results: The selected pH range was applicable to disrupt allergen complexes with highly affine mAbs without compromising allergen integrity. AIs of mAbs accorded with KD values and were unaffected by epitope specificity or the presence of serum proteins. The inter‐assay variability was <4% CV. Protective Mald1‐specific IgG antibodies from individuals with reduced apple allergy showed a higher collective binding strength than that of the non‐protective antibodies of individuals without reduced apple allergy. Conclusion: Acidic disruption of allergen‐antibody complexes may be used to estimate the net‐binding force of polyclonal serum antibodies and eases the investigation of affinity‐related research questions in AIT. [ABSTRACT FROM AUTHOR]

Background: IgE antibodies to cross‐reactive carbohydrate determinants (CCD) are usually clinically irrelevant but they can be a cause of false positive outcomes of allergen‐specific IgE tests in vitro. Their prevalence and levels have been so far cross‐sectionally examined among adult allergic patients and much less is known about their origins and relevance in childhood. Methods: We examined CCD with a cross‐sectional approach in 1263 Italian pollen allergic children (Panallergen in Paediatrics, PAN‐PED), as well as with a longitudinal approach in 612 German children (Multicenter Allergy Study, MAS), whose cutaneous and IgE sensitization profile to a broad panel of allergen extracts and molecules was already known. The presence and levels of IgE to CCD were examined in the sera of both cohorts using bromelain (MUXF3) as reagent and a novel chemiluminescence detection system, operating in a solid phase of fluorescently labelled and streptavidin‐coated paramagnetic microparticles (NOVEOS, HYCOR, USA). Results: IgE to CCD was found in 22% of the Italian pollen allergic children, mainly in association with an IgE response to grass pollen. Children with IgE to CCD had higher total IgE levels and were sensitized to more allergenic molecules of Phleum pratense than those with no IgE to CCD. Among participants of the German MAS birth cohort study, IgE to CCD emerged early in life (even at pre‐school age), with IgE sensitization to group 1 and 4 allergen molecules of grasses, and almost invariably persisted over the full observation period. Conclusions: Our results contribute to dissect the immunological origins, onset, evolution and risk factors of CCD‐sIgE response in childhood, and raise the hypothesis that group 1 and/or 4 allergen molecules of grass pollen are major inducers of these antibodies through an antigen‐specific, T‐B cell cognate interaction. [ABSTRACT FROM AUTHOR]

A study conducted in Singapore examined the outcomes of oral food challenges (OFCs) in children with food allergies. The study found that the risk of anaphylaxis during an OFC was approximately 2%, with respiratory symptoms being the most common reaction. Factors such as a history of allergic rhino-conjunctivitis, known food allergy to the challenge food, and performing a baked milk OFC were associated with an increased risk of anaphylaxis. The study suggests that OFCs can be safely conducted in well-equipped centers with trained personnel. This study provides valuable insights into the actual risk of OFCs and factors contributing to anaphylactic reactions in the local population. [Extracted from the article]

Introduction: Adverse reactions are relatively common during peanut oral immunotherapy. To reduce the risk to the patient, some researchers have proposed modifying the allergen to reduce IgE reactivity, creating a putative hypoallergen. Analysis of recently cloned human IgG from patients treated with peanut immunotherapy suggested that there are three common conformational epitopes for the major peanut allergen Ara h 2. We sought to test if structural information on these epitopes could indicate mutagenesis targets for designing a hypoallergen and evaluated the reduction in IgE binding via immunochemistry and a mouse model of passive cutaneous anaphylaxis (PCA). Methods: X‐ray crystallography characterized the conformational epitopes in detail, followed by mutational analysis of key residues to modify monoclonal antibody (mAb) and serum IgE binding, assessed by ELISA and biolayer interferometry. A designed Ara h 2 hypoallergen was tested for reduced vascularization in mouse PCA experiments using pooled peanut allergic patient serum. Results: A ternary crystal structure of Ara h 2 in complex with patient antibodies 13T1 and 13T5 was determined. Site‐specific mutants were designed that reduced 13T1, 13T5, and 22S1 mAbs binding by orders of magnitude. By combining designed mutations from the three major conformational bins, a hexamutant (Ara h 2 E46R, E89R, E97R, E114R, Q146A, R147E) was created that reduced IgE binding in serum from allergic patients. Further, in the PCA model where mice were primed with peanut allergic patient serum, reactivity upon allergen challenge was significantly decreased using the hexamutant. Conclusion: These studies demonstrate that prior knowledge of common conformational epitopes can be used to engineer reduced IgE reactivity, an important first step in hypoallergen design. [ABSTRACT FROM AUTHOR]

A study published in the journal Clinical & Experimental Allergy found that treatment with the drug dupilumab significantly reduces IgE production in patients with atopic dermatitis (AD) over a median of 2.5 years. The study also showed that IgE levels continue to decrease over time, regardless of the treatment interval. The researchers compared patients who extended the dosing interval of dupilumab to those who did not, as well as healthy volunteers. The findings suggest that dupilumab can effectively reduce IgE levels in AD patients, supporting the decision to extend the dosing interval in well-controlled cases. [Extracted from the article]

Complementary to conventional testing that is based on allergen extracts, molecular allergy diagnosis reduces the need for oral food challenges (OFCs) in food allergy diagnosis. Keywords: allergy; diagnosis; microarray; molecular allergy diagnosis; peanut; skin prick test; specific IgE EN allergy diagnosis microarray molecular allergy diagnosis peanut skin prick test specific IgE 1041 1044 4 10/09/23 20231001 NES 231001 Key Messages We evaluated diagnostic accuracy of ALEX SP 2 sp microarray for peanut allergy in a Turkish population. We, therefore, conclude that SPT, in combination with sIgE to Ara h 2 and Ara h 6 are a highly sensitive and specific approach to diagnose allergy to peanuts. Allergy, diagnosis, microarray, molecular allergy diagnosis, peanut, skin prick test, specific IgE. [Extracted from the article]

In Denmark, tests for specific IgE to penicillins have been used routinely for many years in penicillin allergy investigation. Keywords: anaphylaxis; drug allergy; drug hypersensitivity; immediate type hypersensitivity; penicillin; penicillin allergy; penicillin minor determinants; specific IgE; specific IgE to penicillins EN anaphylaxis drug allergy drug hypersensitivity immediate type hypersensitivity penicillin penicillin allergy penicillin minor determinants specific IgE specific IgE to penicillins 887 890 4 08/14/23 20230801 NES 230801 Key points Specific IgE to penicillins have been recommended in the context of immediate-type allergic reactions. Our study shows that compared to the four commonly used specific IgE assays for penicillins specific IgE MD was positive in a further 29.4% of patients with suspicion of penicillin hypersensitivity, which might increase the sensitivity of penicillin sIgE testing. [Extracted from the article]

Does proactively asking about allergens before ordering improve customer outcomes? There were improvements on all the secondary outcomes: customer satisfaction, customer trust in the business and whether the customer would recommend the business to a friend or family member. Staff proactively asking about allergens increased customer satisfaction, on three different customer satisfaction metrics. [Extracted from the article]

Background: Allergen‐specific immunotherapy (AIT) is the only disease‐modifying treatment approach to change disease‐causing allergens. Hypoallergenic derivatives show promise as potential therapeutics, amongst which BTH2 was designed to induce tolerance against Blomia tropicalis allergy. Our aim was to investigate the hypoallergenicity and immunoregulatory activity of BTH2 in vitro and its therapeutic potential in a mouse model of AIT. Methods: Recombinant Blo t 5 and Blo t 21 allergens and their hybrid derivatives (BTH1 and BTH2) were expressed and purified. IgE binding capacity was tested by ELISA using sera from Brazilian, Colombian, and Ecuadorian subjects. Secretion of cytokines in supernatants from human cell cultures was measured following stimulation with the four recombinants and controls. The capacity of BTH2 to ameliorate allergic airway inflammation induced by B. tropicalis extract was evaluated in a murine model of AIT. Results: rBlo t 5 and rBlo t 21 were identified as major allergens in Latin American patients, and BTH2 had the lowest IgE binding. In vitro stimulation of human cells induced greater levels of IL‐10 and IFN‐γ and reduced the secretion of Th2 cytokines. BTH2 ameliorated allergic airway inflammation in B. tropicalis‐challenged A/J mice, as evidenced by the histopathological and humoral biomarkers: decreased Th2 cytokines and cellular infiltration (especially eosinophils), lower activity of eosinophil peroxidase, an increase in IgG blocking antibodies and strong reduction of mucus production by goblet cells. Conclusions: Our study shows that BTH2 represents a promising candidate for the treatment of B. tropicalis allergy with hypoallergenic, immune regulatory and therapeutic properties. Further pre‐clinical studies are required in murine models of chronic asthma to further address the efficacy and safety of BTH2 as a vaccine against B. tropicalis‐induced allergy. [ABSTRACT FROM AUTHOR]

A study published in the journal Clinical & Experimental Allergy found that polysensitisation, or being sensitized to multiple allergens, is common among patients with allergic rhinitis. The study showed that 81% of patients with allergic rhinitis were polysensitised, and these patients were more likely to have associated asthma and experience more severe symptoms compared to monosensitised patients. The researchers emphasized the importance of molecular diagnosis in managing polysensitised patients, as it provides precise insights into sensitisation patterns. However, the study did not differentiate between true allergy and mere sensitisation, which is crucial in clinical practice, especially when prescribing allergen-specific immunotherapy. The article suggests two diagnostic pathways to confirm allergy: thorough history and allergen-specific challenge. Molecular diagnostics can also assist in defining true allergy, but the results may vary depending on factors such as geographic area, climate, lifestyle, and diet. [Extracted from the article]

This article discusses the prognosis and remission patterns of solid food protein-induced enterocolitis syndrome (FPIES) in children. FPIES is a non-immunoglobulin E (IgE) mediated food allergy that typically occurs in children after the introduction of complementary foods. The study found that most FPIES patients achieve tolerance with age, but the management of determining tolerance to causative foods is still uncertain. The leading cause of solid FPIES in the study was egg yolk, which may be attributed to the Japanese recommendation of early introduction of egg yolk to infants. The study suggests that timely evaluation of tolerance acquisition is crucial to avoid unnecessary elimination in solid FPIES patients, particularly in cases of egg yolk and wheat FPIES. [Extracted from the article]

Background: Clinical and experimental analyses indicate a pathognomonic role for allergen IgE crosslinking through epitope–paratope interactions as a major initial step in the cascade leading to effector cell activation and clinical manifestations of lgE‐mediated food allergies. We aimed to undertake the initial development and assessment of Ara h 2‐specific IgE epitope‐like peptides that can bind to allergen‐specific IgE paratopes and suppress effector cell activation. Methods: We performed biopanning, screening, IgE binding, selection and mapping of peptides. We generated synthetic peptides for use in all functional experiments. ImmunoCAP inhibition, basophil and mast cell activation tests, with LAD2 cells, a human mast cell line were performed. Twenty‐six children or young adults who had peanut allergy were studied. Results: We identified and selected three linear peptides (DHPRFNRDNDVA, DHPRYGP and DHPRFST), and immunoblot analyses revealed binding to lgE from peanut‐allergic individuals. The peptide sequences were aligned to the disordered region corresponding to the loop between helices 2 and 3 of Ara h 2, and conformational mapping showed that the peptides match the surface of Ara h 2 and h 6 but not other peanut allergens. In ImmunoCAP inhibition experiments, the peptides significantly inhibit the binding of IgE to Ara h 2 (p <.001). In basophil and mast cell activation tests, the peptides significantly suppressed Ara h 2‐induced effector cell activation (p <.05) and increased the half‐maximal Ara h 2 effective concentration (p <.05). Binding of the peptides to specific IgEs did not induce activation of basophils or mast cells. Conclusions: These studies show that the indicated peptides reduce the allergenic activity of Ara h 2 and suppress lgE‐dependent basophil and mast cell activation. These observations may suggest a novel therapeutic strategy for food allergy based on epitope–paratop blocking. [ABSTRACT FROM AUTHOR]

Keywords: Allergic inflammation; Alveolar macrophages; Aspergillus fumigatus; CARD9 EN Allergic inflammation Alveolar macrophages Aspergillus fumigatus CARD9 659 663 5 06/09/23 20230601 NES 230601 Key message CARD9 enhances pro-inflammatory immune response, but inhibits pulmonary type 2 immunity after I A. fumigatus i exposure. Moreover, we sorted out alveolar macrophages from WT and CARD9 deficient mice infected with/without I A. fumigatus i , and further confirmed that RelB activation only occurred in CARD9 deficient alveolar macrophages. Simultaneously, we found that the expression of CD80, CD86 and MHC-II were comparable between WT and CARD9 deficient mice with/without I A. fumigatus i exposure, hinting that CARD9 did not affect the antigen presentation capacity of alveolar macrophages. CARD9 balances Aspergillus fumigatus-induced anti-fungal immunity and allergic inflammation. [Extracted from the article]

Keywords: allergen immunotherapy; bioparticle; food allergy; hypoallergenicity; peanut allergy; plant-based particle EN allergen immunotherapy bioparticle food allergy hypoallergenicity peanut allergy plant-based particle 577 581 5 05/10/23 20230501 NES 230501 Key messages Ara h 2 eBPs show reduced IgE binding, effector cell activation, and IgE-facilitated antigen presentation compared to nAra h 2 Ara h 2 eBPs are >10,000-fold hypoallergenic compared to nAra h 2 Ara h 2 eBPs are a promising candidate for peanut allergen immunotherapy To the Editor: Since the early nineties several approaches have been tested to develop safe and effective allergen immunotherapy (AIT) for the treatment of peanut allergy, starting with subcutaneous AIT with aqueous extract, followed by hypo-allergenic major allergens produced in bacteria that were administered rectally. For example, a virus-based particle expressing the peanut allergens Ara h 1 or 2, based on the Cucumber Mosaic Virus, was shown to be hypo-allergenic in a mouse model.[3] Here we report the ground-breaking hypo-allergenicity of a novel non-virus-based microparticle produced in plants, that is, enveloped bioparticles ( I e i BPs) expressing ~3000 copies of Ara h 2 on the surface of each particle. These results indicate that the I e i BPs have a > 10,000-fold reduced capacity to form IgE-Ara h 2 complexes and subsequently activate Th2 cell responses via IgE-facilitated allergen presentation by B cells. [Extracted from the article]

To examine whether air purifiers beneficially modified the adverse influences of prenatal environmental inhalation factors on cIgE, we stratified the study samples by air purifier use (Table 2). Air purifiers can reduce the concentrations of indoor air pollutants and improve asthma control among children.[7] Whether air purifiers modify the association of incense burning with cIgE elevation is unknown. Air purifiers are known to improve indoor air quality.[7] This is the first study to reveal that prenatal use of air purifiers may beneficially modify both the adverse associations of daily incense and >=2 smokers and their cumulative association with cIgE elevation. Daily prenatal household incense burning was positively associated with cord blood IgE (cIgE) elevation. [Extracted from the article]

The most common pattern of poly-sensitization included the allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6 and observed in 17 patients. IgE towards Ara h 8 and Ara h 9 did not correlate with IgE specific to Ara h 1, Ara h 2, Ara h 3 and Ara h 6 ( I r i < .1), and only slightly between each other ( I r i = .43; Figure 1G). The median anti-PE IgE ImmunoCAP concentration was 13.5 kUA/L. Lower ( I p i < .0001) median IgE levels were measured for Ara h 2 (5.6), Ara h 6 (3.7), Ara h 1 (1.2), Ara h 3 (0.13), Ara h 8 (0.85) and Ara h 9 (<0.1). Ara h 2 and Ara h 6 are the most widespread sensitizing allergens. [Extracted from the article]

Background: There are no diagnostic and/or prognostic markers of the treatment outcome in patients receiving allergen immunotherapy (AIT). Although numerous allergen epitopes are known, their value in this context has not been investigated. This paper deals with re‐evaluation of sera from patients who underwent AIT against rBet v 1 for treatment of their soya allergy (BASALIT trial). Objective: To evaluate the diagnostic and/or prognostic potential of allergen epitopes recognition by antibodies from patients with birch‐related soya allergy before and after rBet v 1‐immunotherapy. Methods: PR‐10 epitope‐binding profiles from 34 patients were identified in silico using a statistical peptide phage display at start and at end of AIT. IgE‐ and IgG‐binding to these peptide epitopes was measured in peptide microarrays. Clinical relevance of epitopes was evaluated by comparing these measurements to a number of treatment outcome measures recorded during double‐blind placebo‐controlled food challenge at start and end of AIT. Results: We showed that IgG‐ and IgE‐recognition of peptide epitopes after AIT were surrogate markers of 5 out of 12 analysed treatment outcome measures using this patient cohort. Seven epitopes were identified from multiple PR‐10 allergen sequences. Twenty‐six peptide epitopes were used for IgG and IgE measurements. IgE‐binding to one of the epitopes was associated with stronger intensity of oral tingling/itching after ingesting soya at start of AIT. IgG recognizing two other epitopes at start of AIT could predict decreased Cor a 1‐specific IgE concentration (p =.043) and decreased lip swelling intensity (p =.016) after AIT. Tolerance to increasing amounts of soy at food challenge correlated with IgG‐binding to another epitope at start of AIT (p =.046). Conclusion: IgG‐ and IgE‐binding to peptide epitopes in PR‐10 is a potential indicator of the outcome and clinical course of AIT of soya‐sensitized patients with rBet v 1. [ABSTRACT FROM AUTHOR]

Background: As the prevalence of dog allergy rises, component resolved diagnosis might improve the diagnosis, understanding of the clinical outcomes and the effectiveness of immunotherapy. Considering the paucity of data in adults, the current study characterized the patterns of sensitization to dog molecular allergens in an adult population. Methods: Data were derived from the West Sweden Asthma Study, a population‐based and representative sample of adults from western Sweden. Of the 2006 subjects clinically examined, 313 participants sensitized to whole dog allergen extract were measured for specific immunoglobulin E (sIgE) levels to Can f 1, Can f 2, Can f 3, Can f 4, Can f 5 and Can f 6 using ImmunoCAP™. Polysensitization was defined as sensitization to ≥3 components. Overlapping sensitization was defined as having concomitant sensitization to at least two dog molecular allergen families (lipocalin, albumin or prostatic kallikrein). Results: Of 313, 218 (70%) subjects tested positive to at least one dog allergen component. Sensitization to Can f 1 (43%) was the most common, followed by Can f 5 (33%) among molecular allergens, while sensitization to lipocalins (56%) was the most common among component families. Polysensitization was found in 22% of all participants and was more common in participants with than in those without asthma. Subjects with asthma were less likely to be monosensitized to Can f 5 than those without asthma. Subjects with asthma had higher IgE levels of Can f 3, Can f 4 and Can f 6 than those without asthma. Overlapping sensitizations also differed between those with asthma and allergic rhinitis and those without. Conclusion: Increased knowledge about the sensitization patterns of dog allergen components can aid in defining their role in asthma and rhinitis. In complex clinical cases of dog allergy, a detailed analysis of dog allergen components can provide additional information on the nature of sensitization. [ABSTRACT FROM AUTHOR]

Background: Insights into the IgE cross‐sensitization and possible cross‐reactivity patterns of sera reactive to chlorhexidine (CHX) are still incomplete and are likely to benefit from a functional exploration using a passive mast cell activation test (pMAT). Therefore, we want to study whether the pMAT with CHX‐specific IgE (sIgE) enables to depict effector cell degranulation in response to alexidine (ALX), octenidine (OCT) and/or polyhexamethylene biguanide (PHMB) indicative of cross‐reactivity between these compounds and CHX. Methods: Serum of 10 CHX‐allergic patients, nine individuals with an isolated sIgE CHX and five healthy controls were included. Human cultured mast cells (MCs) were, before and after sensitization, challenged with CHX, ALX, OCT or PHMB. Degranulation was measured via quantification of upregulation of CD63. Results: Mast cell responsiveness to ALX and OCT was demonstrable with 4/10 and 3/10 of the sera of CHX‐allergic patients respectively. Percentage of degranulation varied between 12 and 34% for ALX‐reactive MCs and between 4 and 22% for OCT‐reactive MCs. No reactivity to ALX or OCT was demonstrable when using sera obtained from individuals with an isolated sIgE CHX or from healthy controls. Unlike CHX, ALX and OCT, PHMB turned out to be a direct MC activator via occupation of MRGPRX2. PHMB‐reactive sIgEs were demonstrable in some patients with an isolated sIgE CHX but were unable to trigger PHMB‐induced degranulation in MRGPRX2 knockdown MCs. Conclusion: Mast cells constitute an attractive tool to explore cross‐reactivity between structurally similar compounds. Along with the identification of safe alternatives for the individual patient, the pMAT can advance our insights into sIgE cross‐reactivity patterns including assessment of molecules not yet approved for human use. [ABSTRACT FROM AUTHOR]

The results of the measurements of IgE to hazelnut extract, Cor a 9, 14, 11 and 16 (sum of the N- and C-terminal parts), are shown in Figure 2A. IgE levels of 0.10 kU SB A sb /L or greater to the four hazelnut components were found in 98%, 69%, 65% and 80% of the samples, respectively, with observations distributed across and even beyond the measuring range of the assay. A new vicilin-like allergen in hazelnut giving rise to a spectrum of IgE-binding low-molecular-weight N-terminal fragments Keywords: allergen; allergy; hazelnut; IgE; vicilin EN allergen allergy hazelnut IgE vicilin 1208 1212 5 10/13/22 20221001 NES 221001 Key Messages A new vicilin-like allergen in hazelnut, Cor a 16, is reported A spectrum of IgE-binding vicilin N peptides in hazelnut originates mainly from Cor a 16 Cor a 16 appears as a major allergen in hazelnut-sensitized children Hazelnut is a frequent trigger of food allergic reactions with symptoms ranging from local and mild in individuals with a pollen-related food allergy to severe and even life-threatening among those with a primary food allergy. On the other hand, a database search revealed similarity to segments in the N-terminal region of vicilin-like sequences from macadamia and pecan, suggesting that additional vicilin-related peptides may be present in the IgE-reactive LMW fraction from hazelnut. [Extracted from the article]

Keywords: house dust mites; IgG2; IgG4; specific behaviour of high responders; sublingual immunotherapy; vitamin D EN house dust mites IgG2 IgG4 specific behaviour of high responders sublingual immunotherapy vitamin D 1219 1224 6 10/13/22 20221001 NES 221001 Key messages Seric vitamin D is not a predictive marker of allergy immunotherapy (AIT) efficacy. Indeed, the latter display correlated levels of serum vitamin D before treatment, on the on hand, and of allergen-specific IgG4 and IgG2 before and/or after treatment, on the other hand. As an illustration, serum levels of vitamin D before treatment were plotted against serum levels of I D. pteronyssinus i -specific IgG4, as measured in high and low responders before treatment (Figure 1D,E, respectively) and after treatment (Figure 1F,G, respectively). Moreover, statistically significant positive correlations occurred in high responders only, between, on the one hand, the serum concentration of vitamin D before treatment and, on the other hand, the serum concentrations of HDM-specific IgG4 and IgG2 before and/or after treatment (Table 1). [Extracted from the article]

Keywords: allergen; dosing interval; egg white; food allergy; oral food challenge EN allergen dosing interval egg white food allergy oral food challenge 1114 1117 4 09/02/22 20220901 NES 220901 Key Messages We compared outcomes for raw egg food challenges using 30- or 60-min dosing intervals. Oral food challenge with raw egg: Sixty-minute- compared with 30-minute dosing interval Allergen, dosing interval, egg white, food allergy, oral food challenge. [Extracted from the article]

Background: An increasing interest in the field of molecular diagnosis of allergy has been developed in recent years and it goes to be as the routine in vitro protocol in allergy diagnosis. friendly allergen nano-bead array (FABER) is a new multiplex assay for the evaluation of specific IgE against 244 allergens including whole extracts and allergenic molecules. The research intended to assess the pattern of IgE sensitization to allergenic components of allergens in allergic adults using FABER 244. Methods: Sixty patients with allergic diseases entered this cross-sectional study. Specific IgE to 122 whole allergens extracts and 122 allergenic components were assessed using an allergen nano-bead array (FABER) for all patients. This test includes inhalant and food allergens. Results: Thirty-seven patients were male (61.7%). The mean (SD) age of patients was 30.73(±6.87) years. As the allergen nano-bead array results showed, Lolium perenne (63.3%), Phleum pratense (60%) and Platanus acerifolia (51.7%) were considered as the most common IgE sensitizations to the aeroallergen extracts. Moreover, Lol p 1, Phl p 1.0102 and Cup a 1 were found as the most frequent allergenic components in our allergic patients. Among protein families, CCD-bearing proteins, expansin, cysteine protease and profilin families illustrated the highest allergic sensitization. Conclusions: The results of the present study demonstrated that despite the higher prevalence of sensitization to Salsola kali (47.2%) using extract-based assays in the previous phase of this research, allergenic components of grasses (Lol p 1, Phl p 1.0102), Cup a 1 as well as Sal k1 as the major components of Cupressuss arizonica and Salsola kali showed the higher sensitization, respectively, in adults' allergic patients using FABER test. [ABSTRACT FROM AUTHOR]

Background: Silkworm pupa (SWP) food anaphylaxis has been described frequently in Asian countries. However, false‐positive reactions by skin pricks and serum IgE (sIgE) tests to the extract complicate diagnosis, requiring identification of clinically relevant major allergens. Objectives: In this study, we characterized a novel SWP allergen, Bomb m 4, a 30‐kDa lipoprotein, and evaluated its diagnostic sensitivity. Methods: Bomb m 4 was identified by a proteomic analysis. This recombinant (r)Bomb m 4 was overexpressed in Escherichia coli, and the IgE reactivity by ELISA was compared with other reported allergenic proteins: Bomb m 1 (arginine kinase), 27‐kDa glycoprotein, Bomb m 3 (tropomyosin) using the serum samples from 17 SWP allergic patients and 11 asymptomatic sensitized subjects. Results: rBomb m 4‐specific IgE was recognized by all 17 SWP allergic patients. The 27‐kDa glycoprotein and Bomb m 1 sIgE were found in 35.3% and 0%, respectively, in the SWP allergic patients. ELISA sIgE reactivity increased significantly, when 4 M urea was added in serum samples. However, only 16% inhibition of sIgE reactivity to the whole SWP extract was exhibited by rBomb m 4, whereas more than 93% of self‐inhibition of rBomb m 4 sIgE was obtained, possibly due to the low abundance of Bomb m 4 in the extract. Three linear epitopes (81–95, 191–205 and 224–238 residues) of rBomb m 4 were identified. These epitopes are shown to be released by pepsin digestion. Receiver operator characteristic (ROC) analysis showed the highest diagnostic value of Bomb m 4 followed by Bomb m 1, 27‐kDa glycoprotein and Bomb m 3. Conclusion: Bomb m 4 is the major allergen of SWP allergic patients. It has cryptic epitopes which are exposed to IgE antibodies with digestive enzymes. This recombinant Bomb m 4 allergen permits exact diagnosis of SWP allergy. [ABSTRACT FROM AUTHOR]

Keywords: anaphylaxis; basophil activation test; COVID-19; polyethylene glycol; skin prick test; vaccine EN anaphylaxis basophil activation test COVID-19 polyethylene glycol skin prick test vaccine 812 819 8 06/01/22 20220601 NES 220601 Key Messages Skin prick tests were negative in our patients with reported anaphylaxis to the first dose of mRNA vaccine against COVID-19. Six of the patients (patient number: 22-27/Table 1) reacted with acute onset (within 10-60 min after the first dose) skin symptoms such as urticaria or generalized erythema with or without pruritus with no other objective symptoms. Ten patients were evaluated due to a previous severe reaction to medications, that is, injectable medicines containing PEG/PEG derivatives, which raised suspicion of a PEG/PEG-derivative allergy (patient number: 28-37/Table 2). To end the devastating COVID-19 pandemic and limit mortality, as many as possible need to be safely vaccinated.10 Patients with acute onset vaccine-related systemic reactions to the first COVID-19 vaccine dose, or suspected PEG allergy, should be referred to an allergist or allergy-interested physician. [Extracted from the article]

Of the 153 infants exposed to any AST, 112 were exposed to a single acid suppressive therapy: 77 infants were exposed to H2RA only, 14 were exposed to PPI only, 12 were exposed to Maalox/Mylanta only, and nine were exposed to an unspecified AST only. 153 (19%) infants were exposed to any AST, 45 (6%) were exposed to PPI, 115 (14%) were exposed to H SB 2 sb RA, 24 (3%) were exposed to Maalox/Mylanta in the first 6 months of life, and 13 (2%) were exposed to an unspecified AST. [Extracted from the article]

Keywords: biologics; dupilumab; IgE; IgE trend; omalizumab EN biologics dupilumab IgE IgE trend omalizumab 230 232 3 02/20/23 20230201 NES 230201 Key Messages Changes in total IgE levels while on different biologics in a real Allergy setting are not known Only one-fifth of patients had IgE levels measured before and after biologics initiation, suggesting the need for a standardized follow-up protocol Dupilumab decreased IgE levels the most; none of the patients became IgE deficient To the Editor, Changes in total serum IgE levels or how low the IgE levels decrease while on different biologics used in a real Allergy clinical setting are not well understood. Of note, none of the patients in the studied cohort who had IgE levels checked after a biologic agent initiation became IgE deficient. [Extracted from the article]

Keywords: asthma; emollients; skin barrier; well-child visit; wheeze EN asthma emollients skin barrier well-child visit wheeze 451 455 5 02/24/22 20220301 NES 220301 Key Messages We surveyed emollient use and wheeze and asthma in the children of well-child visits in Osaka and Tokyo, Japan. Our study indicated that the application of emollients on the skin did not affect wheezing but increased asthma events in young children at 3 years of age from a cross-sectional study of well-child visits. Associations of frequent emollient use with wheeze and asthma in young Japanese children: A survey of well-child visits. [Extracted from the article]

Background: Excessive production of IgE plays a major role in the pathology of food allergy. In an attempt to identify anti‐IgE natural products, Arctium Lappa was one of the most effective herbs among approximately 300 screened medicinal herbs. However, little is known about its anti‐IgE compounds. Objective: To identify compounds from Arctium Lappa for targeted therapy on IgE production and explore their underlying mechanisms. Methods: Liquid‐liquid extraction and column chromatographic methods were used to purify the compounds. IgE inhibitory effects were determined on IgE‐producing human myeloma U266 cells, peanut‐allergic murine model and PBMCs from food‐allergic patients. Genes involved in IgE inhibition in PBMCs were studied by RNA sequencing. Results: The main compounds isolated were identified as arctiin and arctigenin. Both compounds significantly inhibited IgE production in U266 cells, with arctigenin the most potent (IC50=5.09μg/mL). Arctigenin (at a dose of 13 mg/kg) markedly reduced peanut‐specific IgE levels, blocked hypothermia and histamine release in a peanut‐allergic mouse model. Arctigenin also significantly reduced IgE production and Th2 cytokines (IL‐5, IL‐13) by PBMCs. We found 479 differentially expressed genes in PBMCs with arctigenin treatment (p <.001 and fold‑change ≥1.5), involving 24 gene ontology terms (p <.001, FDR <0.05); cell division was the most significant. Eleven genes including UBE2C and BCL6 were validated by qPCR. Conclusion: Arctigenin markedly inhibited IgE production in U266 cells, peanut‐allergic murine model and PBMCs from allergic patients by down‐regulating cell division, cell cycle‐related genes and up‐regulating anti‐inflammatory factors. [ABSTRACT FROM AUTHOR]

Background: Deaths attributed to Coronavirus Disease 2019 (COVID‐19) are mainly due to severe hypoxemic respiratory failure. Although the inflammatory storm has been considered the main pathogenesis of severe COVID‐19, hypersensitivity may be another important mechanism involved in severe cases, which have a perfect response to corticosteroids (CS). Method: We detected the serum level of anti‐SARS‐CoV‐2–spike S1 protein‐specific IgE (SP‐IgE) and anti‐SARS‐CoV‐2 nucleocapsid protein‐specific IgE (NP‐IgE) in COVID‐19. Correlation of levels of specific IgE and clinical severity were analysed. Pulmonary function test and bronchial provocation test were conducted in early convalescence of COVID‐19. We also obtained histological samples via endoscopy to detect the evidence of mast cell activation. Result: The levels of serum SP‐IgE and NP‐IgE were significantly higher in severe cases, and were correlated with the total lung severity scores (TLSS) and the PaO2/FiO2 ratio. Nucleocapsid protein could be detected in both airway and intestinal tissues, which was stained positive together with activated mast cells, binded with IgE. Airway hyperresponsiveness (AHR) exists in the early convalescence of COVID‐19. After the application of CS in severe COVID‐19, SP‐IgE and NP‐IgE decreased, but maintained at a high level. Conclusion: Hypersensitivity may be involved in severe COVID‐19. [ABSTRACT FROM AUTHOR]

Background: Clinically complex phenotypes require more and more sophisticated and comprehensive diagnostic approaches, able to discriminate genuine sensitizations from cross‐reactivity. Interpretative complexity of multiplex diagnostic arrays has somewhat limited their diffusion. This study compares two currently available methods, namely ISAC® test and ALEX2® test. Methods: In total, 140 allergic individuals, with a history of atopic dermatitis, adverse food reactions, allergic rhinitis and/or bronchial asthma were studied by Allergy Explorer‐ALEX2® macroarray and ImmunoCAP ISAC112®. Lin's concordance correlation coefficient, intraclass correlation coefficient and Bland–Altman plots were used to verify the agreement between continuous values. Cohen's kappa coefficient (k) was assessed for the molecules available in both tests. The degree of relationship was analysed using Spearman's correlation (quantitative variables) and Pearson's χ2 or Fisher's exact test (categorical variables). Results: A substantial agreement (κ = 0.795) was observed between the two methods with 94,3% concordant results when results were dichotomized as negative or positive, but if double‐negative results were discarded, the agreement dropped to 71%. Conversely, little or no concordance was observed comparing raw data. Considering the 102 molecules shared by both systems, 28/102 (27%) showed an almost perfect agreement (k > 0.81), and concordance was good (k > 0.61) in a further 32 (31%) cases. A perfect to substantial agreement was observed by comparing species‐specific aeroallergens. Heterogeneous results emerged comparing panallergens (co‐recognition ranging from 30% for tropomyosin/serum albumins to 70% for PR‐10/profilin). The correlation among LTP, profilin and PR‐10 assayed with ISAC® was better than ALEX2®, but the latter identified more positive cases due to the wider number of molecules available. The CCD blocker provided by ALEX® test abolishes the carbohydrate determinants signal in 60% of the 33 cases reactive to MUXF3 on the ISAC® test. Conclusion: Despite the excellent concordance of the species‐specific markers, the analysis of the panallergens provided in both methods suggests a better performance of the ISAC® test on those components, while the ALEX2® test, which includes a larger number of allergens, allowing a broader molecular detection. [ABSTRACT FROM AUTHOR]

Keywords: Basophils; chronic spontaneous urticarial; microRNA; omalizumab; response biomarker EN Basophils chronic spontaneous urticarial microRNA omalizumab response biomarker 1648 1652 5 11/30/21 20211201 NES 211201 Key Messages In chronic spontaneous urticaria, a unique basophil microRNA signature associates with complete response to omalizumab. Since microRNA expression levels correlate with clinical response, corroboration of this basophil microRNA signature in a second cohort of CSU patients is needed for their validation as biomarkers. Commercial microRNA panels have been developed to identify the origin or classification of cancers.9 The basophil microRNA expression profiles identified in our study (ie miR-4664-3p, miR-1200, and miR-1236-3p) could serve as a diagnostic panel to guide physicians in selecting CSU patients for omalizumab intervention. [Extracted from the article]

Background: Pollen is one of the most common allergens that cause respiratory allergies worldwide. Pollen grains from poplars have been reported as important sources of pollinosis in many countries. Objective: The aim of the present study was to determine the molecular and immunochemical characterization of Pop n 2, a novel allergen of Populus nigra (P nigra) pollen extract. Methods: In this study, the pollen extract of P nigra was analysed by SDS‐PAGE, and the allergenic profile was determined by IgE immunoblotting and specific ELISA using the sera of twenty allergic patients. The coding sequence of Pop n 2 was cloned and expressed in the Escherichia coli BL21 (DE3) using plasmid the pET‐21b (+). Finally, the expressed recombinant Pop n 2 was purified by affinity chromatography. Results: Pop n 2 belongs to the profilin family with a molecular weight of approximately 14 kDa. Pop n 2 is the most IgE‐reactive protein (about 65%) in the P nigra pollen extract. The cDNA sequencing results indicated an open reading frame 396 bp that encodes 131 amino acid residues. The results of ELISA and Immunoblotting assays showed that recombinant Pop n 2 could react with the IgE antibody in patients' sera, like its natural counterpart. Conclusion: Our data revealed that Pop n 2 is a significant allergen in the P nigra pollen extract. Moreover, we observed that the recombinant Pop n 2 produced by the pET‐21b (+) vector in the E colisystem acts as its natural counterpart. [ABSTRACT FROM AUTHOR]

Background: Atopic diseases are an increasing problem that involve both immediate hypersensitivity reactions mediated by IgE and unique cellular inflammation. Many forms of specific immunotherapy involve the administration of allergen to suppress allergic immune responses but are focused on IgE‐mediated reactions. In contrast, the effect of allergen‐specific immunotherapy on allergic inflammation is complex, not entirely consistent and not well understood. We have previously demonstrated the ability of allergen administered in a nanoemulsion (NE) mucosal adjuvant to suppress IgE‐mediated allergic responses and protect from allergen challenge in murine food allergy models. This activity was associated with decreases in allergen‐specific IL‐10 and reductions in allergic cytokines and increases in regulatory T cells. Objective: Here, we extend these studies to using 2 distinct models, the ovalbumin (OVA) and cockroach (CRA) models of allergic airway disease, which are based predominantly on allergic inflammation. Methods: Acute or chronic allergic airway disease was induced in mice using ovalbumin and cockroach allergen models. Mice received three therapeutic immunizations with allergen in NE, and reactivity to airway challenge was determined. Results: Therapeutic immunization with cockroach or OVA allergen in NE markedly reduced pathology after airway challenge. The 2 models demonstrated protection from allergen challenge‐induced pathology that was associated with suppression of Th2‐polarized immune responses in the lung. In addition, the reduction in ILC2 numbers in the lungs of allergic mice along with reduction in epithelial cell alarmins, IL‐25 and IL‐33, suggests an overall change in the lung immune environment induced by the NE immunization protocol. Conclusions and Clinical Relevance: These results demonstrate that suppression of allergic airway inflammation and bronchial hyper‐reactivity can be achieved using allergen‐specific immunotherapy without significant reductions in allergen‐specific IgE and suggest that ILC2 cells may be critical targets for this activity. [ABSTRACT FROM AUTHOR]

This guideline advises on the management of patients with egg allergy. Most commonly egg allergy presents in infancy, with a prevalence of approximately 2% in children and 0.1% in adults. A clear clinical history will confirm the diagnosis in most cases. Investigation by measuring egg‐specific IgE (by skin prick testing or specific IgE assay) is useful in moderate‐severe cases or where there is diagnostic uncertainty. Following an acute allergic reaction, egg avoidance advice should be provided. Egg allergy usually resolves, and reintroduction can be achieved at home if reactions have been mild and there is no asthma. Patients with a history of severe reactions or asthma should have reintroduction guided by a specialist. All children with egg allergy should receive the MMR vaccine. Most adults and children with egg allergy can receive the influenza vaccine in primary care, unless they have had anaphylaxis to egg requiring intensive care support. Yellow Fever vaccines should only be considered in egg‐allergic patients under the guidance of an allergy specialist. This guideline was prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI) and is intended for allergists and others with a special interest in allergy. The recommendations are evidence based. Where evidence was lacking, consensus was reached by the panel of specialists on the committee. The document encompasses epidemiology, risk factors, diagnosis, treatment, prognosis and co‐morbid associations. [ABSTRACT FROM AUTHOR]

Gene expression in whole peripheral blood differed between peanut sensitized, allergic and non-allergic, non-sensitized subjects. This study harnessed whole blood RNA sequencing technology to examine gene expression differences among infants at high risk for peanut allergy who are peanut allergic (PA), peanut sensitized but orally tolerant (PST) and peanut non-allergic (PNA). T-cell activation genes differentially expressed at birth in CD4+ T-cells from children who develop IgE food allergy. [Extracted from the article]

The only I D i . I melanogaster i allergen confirmed until now is LSP-2 (hexamerin),5 and however, the identification of this allergen was only shown by comparing the IgE immunoblot band pattern with the biding profile of an anti-LSP-2 antibody. This protein is a relevant allergen described in Crustacea.7 Although patient did not refer allergic symptoms after eating shellfish, sensitization was not determined because she refused a prick-by-prick test with shrimp. Only two ADHs have been described as allergens to date, both from fungi; Cand a 1, in I Candida albicans i 9 and Cur l ADH in I Curvularia lunata i .10 ADHs are glycolytic enzymes involved in NAD+regeneration and in the I D i . Keywords: allergens and epitopesss; IgE; occupational allergies; rhinitis EN allergens and epitopesss IgE occupational allergies rhinitis 1387 1390 4 10/01/21 20211001 NES 211001 Key Messages We reported a case of occupational allergy to I Drosophila melanogaster i mediated by four allergens. [Extracted from the article]

A, total IgE level, B, sIgE level to Timothy grass pollen and C, sIgE level to birch pollen. In conclusion, we examined the seasonality of sIgE level to grass and birch pollens and total IgE level in general adult populations using data from a cross-sectional multinational study. Previous work in populations found higher specific IgE levels in the relevant pollen season. A, sIgE level to Timothy grass pollen and B, sIgE level to birch pollen. [Extracted from the article]

BackgroundEvidence suggests that exposure to polycyclic aromatic hydrocarbons (PAHs) increases atopy; it is unclear how PAH exposure is linked to increased severity of atopic diseases.ObjectiveWe hypothesized that ambient PAH exposure is linked to impairment of immunity in atopic children (defined as children with asthma and/or allergic rhinitis) from Fresno, California, an area with elevated ambient PAHs.MethodsWe recruited 256 subjects from Fresno, CA. Ambient PAH concentrations (ng/m(3) ) were measured using a spatial-temporal regression model over multiple time periods. Asthma diagnosis was determined by current NHLBI criteria. Phenotyping and functional immune measurements were performed from isolated cells. For epigenetic measurements, DNA was isolated and pyrosequenced.ResultsWe show that higher average PAH exposure was significantly associated with impaired Treg function and increased methylation in the forkhead box protein 3 (FOXP3) locus (P < 0.05), conditional on atopic status. These epigenetic modifications were significantly linked to differential protein expression of FOXP3 (P < 0.001). Methylation was associated with cellular functional changes, specifically Treg dysfunction, and an increase in total plasma IgE levels. Protein expression of IL-10 decreased and IFN-γ increased as the extent of PAH exposure increased. The strength of the associations generally increased as the time window for average PAH exposure increased from 24 hr to 1 year, suggesting more of a chronic response. Significant associations with chronic PAH exposure and immune outcomes were also observed in subjects with allergic rhinitis.Conclusions and clinical relevanceCollectively, these results demonstrate that increased ambient PAH exposure is associated with impaired systemic immunity and epigenetic modifications in a key locus involved in atopy: FOXP3, with a higher impact on atopic children. The results suggest that increased atopic clinical symptoms in children could be linked to increased PAH exposure in air pollution.

Background: Type 2 inflammation is common in numerous atopic/allergic diseases and can be identified by elevated biomarker levels. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin‐4 and interleukin‐13, key and central drivers of type 2 inflammation. Objective: Assessment of dupilumab effect on type 2 inflammatory biomarkers in atopic dermatitis (AD), asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and eosinophilic esophagitis (EoE). Methods: Data were extracted from three randomized placebo‐controlled trials of dupilumab in AD (NCT02277743, N = 671; NCT02277769, N = 708; NCT02260986, N = 740); and one each in asthma (NCT02414854, N = 1902); CRSwNP (NCT02898454, N = 448); and EoE (NCT02379052, N = 47). Biomarkers assessed were serum thymus and activation‐regulated chemokine (TARC), plasma eotaxin‐3, serum total immunoglobulin E (IgE), serum periostin and blood eosinophil count. Results: Dupilumab versus placebo significantly suppressed most type 2 inflammatory biomarker levels across all studies/indications where data were assessed. Reductions in serum TARC, plasma eotaxin‐3 and serum periostin occurred rapidly, whereas reductions in serum total IgE were more gradual. Across diseases, at the end of treatment, median percentage change from baseline in TARC levels ranged from −24.8% to −88.6% (placebo +2.6% to −53.6%); −38.2% to −51.5% (placebo +8.3% to −0.16%) in eotaxin‐3; −24.8% to −76.7% (placebo +8.3% to −4.4%) in total IgE; and −13.6% to −41.1% (placebo +10.1% to −6.94%) in periostin levels. Blood eosinophil responses to dupilumab varied by disease, with minimal changes in AD in the SOLO studies (median percentage change from baseline to end of treatment: 0% [95% CI: −15.8, 0]); transient increases followed by decreases to below‐baseline levels in asthma (−14.6% [−20.0, −7.7]) and CRSwNP (−29.4% [−40.0, −16.3]); and significant decreases in EoE (−50.0% [−50.0, −33.3]). Conclusion and clinical relevance: Dupilumab reduced levels of type 2 biomarkers across clinical studies in patients with AD, asthma, CRSwNP and EoE. [ABSTRACT FROM AUTHOR]

Secondly, we applied the integrated AUC method to quantify the amount of peanut or hazelnut allergenic foods in serum after ingestion peanut or hazelnut flour in six/four healthy subjects. GLO:ETE/01jul21:cea13899-fig-0001.jpg PHOTO (COLOR): 1 Concentration of allergen in serum (ng/mL) before and 1 hour after ingestion of 100 g of peanut (left) and 2 hours after ingestion of 200 g of hazelnut (right). This was achieved by spiking of serum with peanut and hazelnut extracts at different concentrations followed by the integrated AUC method to estimate allergen concentrations in serum. [Extracted from the article]

Summary: Background: Serum inhibition of allergen‐specific IgE has been associated with competing IgG4 and non‐specific polyclonal IgE. In allergen immunotherapy, beneficial responses have been associated with high IgG4/IgE ratios. Helminths potentiate antibody class switching to IgG4 and stimulate polyclonal IgE synthesis; therefore, we hypothesized a role for helminth‐associated IgG4 and total IgE in protection against atopic sensitization and clinical allergy (asthma) in tropical low‐income countries. Methods: Among community residents of Ugandan rural Schistosoma mansoni (Sm)–endemic islands and a mainland urban setting with lower helminth exposure, and among urban asthmatic schoolchildren and non‐asthmatic controls, we measured total, Schistosoma adult worm antigen (SWA)–specific, Schistosoma egg antigen (SEA)–specific and allergen (house dust mite [HDM] and German cockroach)–specific IgE and IgG4 by ImmunoCAP® and/or ELISA. We assessed associations between these antibody profiles and current Sm infection, the rural‐urban environment, HDM and cockroach skin prick test (SPT) reactivity, and asthma. Results: Total IgE, total IgG4 and SWA‐, SEA‐ and allergen‐specific IgE and IgG4 levels were significantly higher in the rural, compared to the urban setting. In both community settings, both Sm infection and SPT reactivity were positively associated with allergen‐specific and total IgE responses. SPT reactivity was inversely associated with Schistosoma‐specific IgG4, allergen‐specific IgG4/IgE ratios and total IgE/allergen‐specific IgE ratios. Asthmatic schoolchildren, compared with non‐asthmatic controls, had significantly higher levels of total and allergen‐specific IgE, but lower ratios of allergen‐specific IgG4/IgE and total IgE/allergen‐specific IgE. Conclusions and clinical relevance: Our immuno‐epidemiological data support the hypothesis that the IgG4–IgE balance and the total IgE–allergen‐specific IgE balance are more important than absolute total, helminth‐ or allergen‐specific antibody levels in inhibition of allergies in the tropics. [ABSTRACT FROM AUTHOR]

CONCLUSION Multiple problems exist in the management of patients with anaphylaxis: Some are medical with a paucity of trained allergists in most European countries. Anaphylaxis has gained worldwide attention following allergic reactions to COVID vaccines.1 Guidelines have been renewed.2 The use of the International Classification of Diseases, 11th Revision (ICD-11), containing the first ever chapter about hypersensitivity conditions has probably increased the reported number of anaphylaxis-related deaths.3 Public and medical awareness of anaphylaxis and its early recognition should improve prevention and outcomes.2 As members of the former Ethics Committee of the European Academy of Allergy and Clinical Immunology (EAACI), we aimed to discuss anaphylaxis through basic principles of medical ethics such as I beneficence i , I non-maleficence i , I autonomy i and I justice i 4,5 (Figure 1). Isolated skin involvement with urticaria or angioedema may be misdiagnosed as a food-related anaphylaxis, instigating serious consequences as patients would have to live with unnecessary permanent vigilance and anxiety. [Extracted from the article]