Allergic Individuals Research Articles

Impact psychosocial de l’allergie à l’arachide en France : résultats de l’étude APPEAL

Peanut allergy (PA) is common and often involved in the most severe anaphylactic reactions. The aim of this survey was to investigate the psychosocial impact of PA in France. MethodsThe results from French participants to the pan-European study Allergy to Peanuts imPacting Emotions And Life (APPEAL) designed to assess the psychosocial impact of PA are reported here. Participants were adults affected by PA directly or indirectly (caregivers) and they completed an online questionnaire. ResultsIn all, 198 responders (60 adults with PA, 138 caregivers). 88% stated that PA affects their daily activities, and 74% felt isolated as a result of living with PA. Feelings of worry about exposure to peanuts on social occasions where food is involved was reported by 91%. A total of 44% reported some restrictions in their job options, 85% in socializing. Psychological impact of PA included responders feeling emotions of frustration (89%), uncertainty (87%), and stress (93%). Of the 115 responders prescribed adrenaline auto-injectors, 62 (54%) had their device always or very frequently; 32 (28%) and 21 (18%) had the device rarely or never; 72 (63%) had never used one and most felt not at all confident (31%) or very little confidence (27%) in knowing when and how to use one. ConclusionsThese results demonstrate the psychosocial impact of PA on allergic individuals and their caregivers in France, and highlight the need to include a psychological evaluation during personalized care and treatment of individuals with PA.

Peanut Can Be Used as a Reference Allergen for Hazard Characterization in Food Allergen Risk Management: A Rapid Evidence Assessment and Meta-Analysis

Regional and national legislation mandates the disclosure of “priority” allergens when present as an ingredient in foods, but this does not extend to the unintended presence of allergens due to shared production facilities. This has resulted in a proliferation of precautionary allergen (“may contain”) labels (PAL) that are frequently ignored by food-allergic consumers. Attempts have been made to improve allergen risk management to better inform the use of PAL, but a lack of consensus has led to variety of regulatory approaches and nonuniformity in the use of PAL by food businesses. One potential solution would be to establish internationally agreed “reference doses,” below which no PAL would be needed. However, if reference doses are to be used to inform the need for PAL, then it is essential to characterize the hazard associated with these low-level exposures. For peanut, there are now published data relating to over 3000 double-blind, placebo-controlled challenges in allergic individuals, but a similar level of evidence is lacking for other priority allergens. We present the results of a rapid evidence assessment and meta-analysis for the risk of anaphylaxis to a low-level allergen exposure for priority allergens. On the basis of this analysis, we propose that peanut can and should be considered an exemplar allergen for the hazard characterization at a low-level allergen exposure.

Rationale, design and preliminary results of a panel study investigating six health effects of airborne pollen: the EPOCHAL study

BACKGROUND AND AIM: While airborne pollen is widely recognized as a seasonal cause of sneezing and itchy eyes, its systemic health effects on pulmonary function, cardiovascular health, sleep quality, and cognitive performance are less well-established. Further, it is likely that the public health impact of pollen may increase in the future due to two trends in the last decades: higher population prevalence of pollen sensitization as well as earlier, longer, and more intense pollen seasons, attributed to climate change. No observational study in adults has studied dose-response relationships between pollen concentration and health yet. Most studies did not confirm allergy status objectively, lacked statistical power, or were highly restrictive in their inclusion criteria, and therefore not representative of the real-world allergic population. METHODS: This work describes an overview of epidemiological research on pollen and health so far, outlining the rationale and research design of the EPOCHAL study (Effects of Pollen on Cardiorespiratory Health and ALlergies). EPOCHAL aims to relate ambient concentrations of different pollen species to six specific health outcomes. In a panel of 400 allergic and non-allergic individuals, heart rate variability and blood pressure (cardiovascular outcomes), lung function and airway inflammation (pulmonary outcomes), performance in various cognitive domains, allergic symptom severity as well as sleep and health-related quality of life are being measured repeatedly (6-16 times) over 6 weeks. RESULTS:Participant recruitment has started in March 2021 and preliminary results will be available. We aim to uncover and characterize dose-response relationships between different allergenic species of pollen and health, while evaluating concentration thresholds, linearity and plateaus. We will further explore vulnerable population subgroups, defined by sensitization profiles, demographics and comorbidities such as asthma. CONCLUSIONS:A gain of knowledge in pollen-health outcome relationships is critical to inform future environmental and health policies, provide better symptom forecasts and improve personalized prevention and medicine. KEYWORDS: Allergies, environmental epidemiology, cardiovascular diseases, respiratory outcomes, greenspace, climate

An international seroprevalence survey of the IgE sensitisation to the Dermatophagoides farinae house dust mite and two of its major allergens (Der f 2, Zen 1) in atopic dogs.

BackgroundDogs with atopic dermatitis are often immunoglobulin (Ig)E‐sensitised to Dermatophagoides farinae (Df) house dust mites, yet limited data exist on the sensitisation rates to the individual Df allergens, Der f 2 and Zen 1.ObjectivesTo determine the IgE sensitisation rates to Df, Der f 2 and Zen 1 in atopic dogs from geographically diverse countries.AnimalsSerum was collected from 32 laboratory dogs in Japan, and 837 atopic dogs from 11 countries from five continents: Asia (Japan, Thailand, Taiwan), Europe (Italy, Latvia, the Netherlands, UK), North America (USA), South America (Argentina, Brazil) and Africa (South Africa).Methods and materialsWe determined Df‐, Der f 2‐ and Zen 1‐specific IgE levels by ELISA. Correlations between the IgE values for these three allergens were calculated.ResultsThe IgE seropositivity rates for Df varied between 74% (Argentina) and 100% (the Netherlands, Thailand, South Africa), those for Der f 2 between 12% (Argentina) and 88% (South Africa), and for Zen 1 between 70% (Argentina) and 100% (the Netherlands). Apart from the especially low seropositivity rate for Der f 2‐specific IgE in Argentina, the percentage of IgE sensitisation varied little between countries. There was significant correlation between the IgE levels to these three allergens which was highest between Df and Zen 1, and lowest between Zen 1 and Der f 2.Conclusions and clinical relevanceThe IgE sensitisation to Df is geographically widespread. Der f 2 and Zen 1 are major allergens for dogs in almost all countries where this was evaluated.

Update on Contact Sensitization in the Older Adult Population.

Little is known about the epidemiology of allergic contact dermatitis in the aging US population. The aim of this study was to describe patch test results in a cohort of older adult patients evaluated in a patch testing clinic in a tertiary medical center. This study was a retrospective analysis of patch test results of adults 65 years and older from February 2013 to December 2019. Data from a total of 169 patients 65 years and older were analyzed. Of these patients, 84.6% (143/169) had 1 or more positive reactions on patch testing, 84.6% (121/143) of which were felt to be clinically relevant and received a final diagnosis of allergic contact dermatitis. The most common allergen categories were fragrances (30.1%), preservatives (20.8%), metals (11.0%), medicaments (8.3%), and textile dyes (6.5%). The most common individual allergens were Myroxylon pereirae resin (balsam of Peru), hydroperoxide of linalool, methylisothiazolinone, nickel sulfate, and fragrance mix I. Personal products were by far the most common presumed source of allergen exposure. Allergic contact dermatitis is a common diagnosis in the older adult population, and patch testing with allergen avoidance counseling can be an important diagnostic step and potential cure for this allergic condition.

Memory and naïve gamma delta regulatory T-cell gene expression in the first 24-weeks of peanut oral immunotherapy

BackgroundPeanut oral immunotherapy (POIT) has provided desensitization to peanut allergic individuals. Limited immunological evaluation exists during the first 24-weeks of POIT. ObjectiveRegulatory T-cells (Tregs) are antigen induced immunosuppressive T-cells important in establishing tolerance. Delineation of early immunologic changes contributing to the development of peanut desensitization would help clarify the mechanism of action in POIT. We performed single-cell RNA sequencing (scRNAseq) on Tregs in pediatric subjects undergoing POIT during the first 24-weeks of therapy to evaluate early immunological changes induced by POIT. MethodsPBMC samples from peanut allergic subjects between 5 and 12 years of age enrolled in a Phase 1/2a POIT study were collected and analyzed at 0, 6, and 24-weeks after POIT initiation and samples were compared to healthy non-peanut allergic controls. Tregs were enriched from PBMCs and scRNAseq analysis performed. Cell Ranger 3.1.0 (10× Genomics) was utilized to identify cell clusters and differentially expressed genes, and results were analyzed with Seurat suite version 3.0.0. ResultsGene analysis revealed 10 major clusters corresponding to different cell types observed to change during POIT when compared to the healthy, non-peanut-allergic state. scRNAseq analysis of Tregs revealed strong CD3G expression correlating with gdTregs. scRNAseq analysis of gdTregs revealed dynamic changes occurring within the first 6-weeks of treatment and cell frequencies of naïve and memory gdTregs at 24-weeks of treatment reducing to levels similar to healthy controls. Analysis of transcriptomic cell identity analysis using SingleR showed gene expression in gdTregs similar to healthy control after 24-weeks of POIT treatment. scRNAseq analysis revealed alterations in gene expression for memory and naïve gdTregs during this timeframe. Specifically, expression of OX40R (TNFRSF4), GITR (TNFRSF18), TGFB1, CTLA4, ISG20, CD69 were upregulated in memory gdTregs compared to naive gdTregs by 24-weeks of POIT, while IL7R and SELL were downregulated in memory gdTregs compared to naïve gdTregs. ConclusionsThere are specific expression profiles of peripheral naïve and mature gdTreg cells in peanut allergic patients undergoing POIT in the first 24-weeks of treatment implicating pathways involved in maintenance of immune homeostasis. gdTreg cells may contribute to the tolerogenic effect of POIT within the first 24-weeks of POIT treatment. These findings suggest that gdTregs cells may be an early marker of desensitization in subjects undergoing POIT.

Distinct differences in analytical performance of two commercially available assays for specific IgE to egg white and house dust mite allergens

BackgroundMeasurements of allergen-specific IgE antibodies with different manufacturers’ assays show modest or poor agreement. This study compares analytical performance of specific IgE tests for whole allergen extracts and individual allergen components of two assay systems, IMMULITE and ImmunoCAP, using human sera as well as monoclonal antibodies.MethodsComparisons were performed for specific IgE to house dust mite (HDM, n = 44), egg white (EW, n = 36) and the allergen components rDer p 1, rDer p 2, nGal d 1, nGal d 2 and nGal d 4 in human sera and with monoclonal mouse/human chimeric IgE antibodies specific for the same allergen components. Competitive interference with IgE measurement was investigated using allergen-specific monoclonal IgG and IgG4 antibodies.ResultsMeasurements of IgE to HDM and EW in serial dilutions of human sera revealed weaker dilution linearity with IMMULITE than with ImmunoCAP. Analysis of five different monoclonal IgE antibodies with total and specific IgE assays, expected to return similar levels, gave an average specific/total IgE ratio of 0.96 (range 0.71–1.14) with ImmunoCAP and 1.89 (range 0.76–2.85) with IMMULITE, indicating overestimation of specific IgE by IMMULITE. With the EW IgE tests of both assay systems, measurements of a chimeric anti-Gal d 2 IgE antibody were unaffected by a competing mouse IgG antibody. While the same was true for measurement of a chimeric anti-Der p 1 IgE antibody using the HDM test in ImmunoCAP, a suppression of measured concentrations by up to 42% was observed in IMMULITE. Similarly, measurement of HDM-specific IgE in human sera by ImmunoCAP was unaffected by a competing monoclonal anti-Der p 2 IgG4 antibody while IMMULITE displayed a reduction of HDM-specific IgE values by up to 30%.ConclusionsIn this evaluation of analytical performance of two widely used assay systems, ImmunoCAP showed higher accuracy in quantitation of specific IgE and greater resistance against competing allergen-specific non-IgE antibodies which may arise through natural or dietary exposure, or as a result of allergen immunotherapy treatment.

Anaphylaxis to foods purchased from food establishments in Australia.

Food establishments that sell non-packaged foods are not required to have a food label directly on the food product detailing the ingredients. This practice could increase the risk of anaphylaxis among individuals with food allergy. The aim of the study is to understand whether anaphylaxis occurs commonly in individuals with food allergy as a consequence of eating food products purchased from food establishments. We undertook an anonymous on-line cross-sectional survey of food allergic individuals over a 9-month period. Anaphylaxis was defined as reported symptoms consistent with the Australasian Society of Clinical Immunology and Allergy definition of anaphylaxis. A total of 268 responses were received over the study period and 264 consented and completed the questionnaire. Among our survey participants, the rate of anaphylaxis to food purchased from establishments was 27% (n=67/246, 95% confidence interval 21.8-33.3%). Of those who reported an anaphylaxis (n=67), 87% reported informing staff of their/their dependents food allergy/s. Most (81%) reported that they would like to see additional information, such as listing of allergen information next to dishes on the menu and 61% reported that staff pro-actively asking about food allergies would be beneficial. Anaphylaxis from food purchased at food establishments is not uncommon despite a high proportion of individuals declaring their food allergy to staff. Consumers with food allergy would like to see allergen information listed on the menus and for staff to proactively enquire about food allergies. A food allergen matrix that is regularly checked/updated so staff and consumers have easy access to information on menu items and common allergens is required.

Mosquitoes: Important Sources of Allergens in the Tropics.

There are more than 3,000 mosquito species. Aedes aegypti, Ae. communis, and C. quinquefasciatus are, among others, three of the most important mosquito allergen sources in the tropics, western, and industrialized countries. Several individuals are sensitized to mosquito allergens, but the epidemiological data indicates that the frequency of sensitization markedly differs depending on the geographical region. Additionally, the geographical localization of mosquito species has been affected by global warming and some mosquito species have invaded areas where they were not previously found, at the same time as other species have been displaced. This phenomenon has repercussions in the pathogenesis and the accuracy of the diagnosis of mosquito allergy. Allergic individuals are sensitized to mosquito allergens from two origins: saliva and body allergens. Exposure to saliva allergens occurs during mosquito bite and induces cutaneous allergic reactions. Experimental and clinical data suggest that body allergens mediate different manifestations of allergic reactions such as asthma and rhinitis. The most studied mosquito species is Ae. aegypti, from which four and five allergens of the saliva and body, respectively, have been reported. Many characterized allergens are homologs to arthropod-derived allergens, which cause strong cross-reactivity at the humoral and cellular level. The generalized use of whole body Ae. communis or C. quinquefasciatus extracts complicates the diagnosis of mosquito allergy because they have low concentration of saliva allergens and may result in poor diagnosis of the affected population when other species are the primary sensitizer. This review article discusses the current knowledge about mosquito allergy, allergens, cross-reactivity, and proposals of component resolved approaches based on mixtures of purified recombinant allergens to replace saliva-based or whole-body extracts, in order to perform an accurate diagnosis of allergy induced by mosquito allergen exposure.

The role of the allergist in the management of eosinophilic esophagitis.

The purpose of this review is to provide the current understanding of the role of allergens/antigens, the use of allergy testing, and to elucidate the role of the allergist in the management of eosinophilic esophagitis (EoE). EoE is a T2 immune disorder that is part of the atopic march. EoE patients commonly have multiple concurrent allergic disorders. Recent studies demonstrate that, like other allergic diseases, epithelial barrier dysfunction plays a key role in EoE pathogenesis. Aero- and food allergens have been identified as EoE triggers. EoE management includes the assessment and avoidance of its instigating antigens. Due to the integrated T2 immune response in an allergic individual, proper EoE care should include the control of underlying atopic disorders. EoE is a complex disease that is optimally managed by a multidisciplinary approach. This review provides an update on the role of the allergist in the clinical management of EoE.

Component-Resolved Diagnosis of American Cockroach (Periplaneta americana) Allergy in Patients From Different Geographical Areas

Background: Manifestation of respiratory allergy to American cockroach (Periplaneta americana) is prominent in the subtropical and tropical areas. However, co-existing perennial indoor inhalant allergies frequently compromise clinical diagnosis of cockroach allergy, and the analysis of sensitization pattern is limited by the lack of Periplaneta allergens widely available for component-resolved diagnostics (CRD).Objective: To evaluate a collection of previously described recombinant Periplaneta allergens for CRD in cockroach allergy.Methods: A panel of nine recombinant Periplaneta allergens (Per a 1–5, 7–10) was generated, purified, and subjected to physicochemical characterization by applying circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), amino acid (AA) analysis, and mass spectrometry (MS). Patients (n = 117) from India, Korea, Venezuela, and Iran, reporting perennial respiratory indoor allergies with IgE sensitization to cockroach (P. americana and/or Blattella germanica), were included. The sensitization profile was monitored by the experimental ImmunoCAP testing.Results: ImmunoCAP testing confirmed IgE sensitization to Periplaneta and/or Blattella extract in 98 of 117 patients (r = 0.95). Five out of 117 patients were sensitized to only one of the two cockroach species. Within the whole study group, the prevalence of sensitization to individual allergens varied from 4% (Per a 2) to 50% (Per a 9), with the highest IgE values to Per a 9. Patients from four countries displayed different sensitization profiles at which Per a 3 and Per a 9 were identified as major allergens in India and Korea. Periplaneta-derived lipocalin and myosin light chain were characterized as new minor allergens, designated as Per a 4 and Per a 8. Periplaneta extract showed higher diagnostic sensitivity than all individual components combined, suggesting the existence of allergens yet to be discovered.Conclusion: Utilization of a panel of purified Periplaneta allergens revealed highly heterogeneous sensitization patterns and allowed the classification of lipocalin and myosin light chain from Periplaneta as new minor allergens.

Adding the variable of environmental complexity into the COVID-19 pandemic equation.

In a recently published data-orientedstudyin March 2021, a relationship between SARS-CoV-2 infection rates and airborne pollen concentrationswas detected [1]. The studyincluded a data compilation of airborne pollen concentrations and SARS-CoV-2 infection numbers across 31 countries from both hemispheres and all inhabited continents from an inter-disciplinary team consisting of 154 scientists. The salient finding wasa significant and positive correlation between SARS-CoV-2 infection rates and airborne pollen concentrations in the spring of 2020 for the majority of examined countries, in synergy with air temperature and/or relative humidity (Fig. 1).

Epigenetic regulation of epithelial dectin-1 through an IL-33-STAT3 axis in allergic disease.

Allergic diseases arise in susceptible individuals in part because of decrements in protective pathways. The mechanism by which these anti-inflammatory molecules become repressed remains unclear. We have previously reported that epithelial dectin-1 prevents aberrant type 2 responses and is downregulated in the epithelium of allergic patients. Here, we report that dectin-1 is constitutively expressed by the respiratory epithelium in humans and that IL-33 specifically acts as a repressor of dectin-1. Mechanistically, this occurs via IL-33-dependent STAT3 activation and the subsequent repression of the dectin-1gene, CLEC7A. We have identified a novel enhancer region upstream of the proximal promoter of CLEC7A that is only accessible in epithelial cells, but not in hematopoietic cells. Epigenetic repression of CLEC7A through this newly identified locus, downstream of an aberrant IL-33-STAT3 axis, occurs in the epithelium of allergic individuals. Collectively, our data identify a mechanism of epigenetic fine-tuning of dectin-1 expression in epithelial cells that may participate in allergenicity.

Serum allergen-specific IGE to common aeroallergens among allergic rhinitis patients in Egypt

BackgroundAllergic rhinitis is the most prevalent allergic disease, and the prevalence and sensitization patterns differ among countries. Identifying the most common inhalant allergen in each region plays a key role in the diagnosis and management of allergic rhinitis. There are no data available about the most prevalent aeroallergen among allergic rhinitis patients in Egypt. The aim of this study is to evaluate the prevalence of positive serum allergen-specific IGE to common inhalant allergens among allergic rhinitis patients in Egypt. A cross-sectional study was conducted on 354 allergic rhinitis patients, serum allergen-specific IGE was measured by using the Immuno CAP system to 16 common regional aeroallergens including (pollens, mite, molds, animal dander, and cockroach).ResultsThe overall rate of sensitization to any allergen was 74.6%. Dermatophagoides pteronyssinus, birch pollens, and Dermatophagoides farina were the most prevalent allergens (29.7%, 23.7%, and 18.6%), respectively. Cladosporuim molds were the least prevalent individual allergens (1.7%).ConclusionOur data suggest that Dermatophagoides pteronyssinus and birch pollens were the predominant allergen sources among allergic rhinitis patient in Egypt.

Pfizer-BioNTech COVID-19 Vaccine Tolerance in Allergic versus Non-Allergic Individuals.

Individuals with a history of allergy are potentially at risk of suffering from adverse effects after COVID-19 vaccination. We sought to assess the tolerance towards the Pfizer-BioNTech vaccine in allergic patients. To address this issue, we used a questionnaire conducted on-line in a group of medical professionals who were vaccinated with the Pfizer-BioNTech vaccine. A total of 1808 respondents, out of whom 1707 received two doses of the vaccine, returned the questionnaire. Local reactions after injection were more frequent in allergic individuals after both doses (swelling p = 0.0003). Systemic adverse events (AE-SYS) occurred more often after the second than the first dose in both groups (allergic persons: 77.29% vs. 41.06%); vomiting and arthralgia occurred more often in allergic subjects (p = 0.0009). AE-SYS in allergic individuals lasted longer than in non-allergic ones after the first (p = 0.01) and the second dose (p = 0.0009). Allergic reactions after vaccination were reported more frequently in allergic subjects: after the first dose (p = 0.00001) and after the second dose (p = 0.001). Rhinitis was the most frequent symptom observed more often in allergic patients. No severe allergic reactions occurred during the full cycle of vaccination. Although the Pfizer-BioNTech vaccine is tolerated worse by allergic than non-allergic individuals, the occurring adverse symptoms are mild and do not preclude a successful completion of the vaccination cycle. The presence of symptoms suggestive of allergy does not constitute a condition of increased risk of developing clinically significant adverse events following Pfizer COVID-19 vaccination.

Performance of allergen testing in a survey of frozen meals and meals ready-to-eat (MREs)

ABSTRACT A 7-plex immunoassay capable of detecting cashew, egg, hazelnut, milk, peanut, shrimp, and soy allergens was used to screen meals ready-to-eat (MREs) and frozen meals that contained meat or poultry. The same food matrices were also evaluated using single individual allergen immunoassays. Multiplex and single allergen test results were compared with the allergen declared on the food label, which was considered the standard. For both the frozen meals (n = 113) and MREs (n = 24) each analytical method failed to detect allergens that were declared on product labels, but only in frozen meals were allergens detected that were not declared on the label. Undeclared allergens were detected for egg in 1.8% (2/113) and for soy in 7.1% (8/113) of frozen meals. Labelled allergens were not detected in 0.9% (1/113) of milk, 4.4% (5/113) of egg, and 15% (17/113) of soy allergens in frozen meals. Assay performance for evaluating allergens in MREs was poor.

Molecular diagnosis in cat allergy.

Domestic cats represent one of the most common sources of indoor allergens. All over the world, many households own cats, whose allergens are persistent and widespread. Cat allergy itself is frequent, and its symptoms vary from rhinoconjunctivitis to life-threatening asthma. In vitro diagnosis using precision medicine allergy immunoassays is important because natural cat dander extracts may differ in quality and quantity of some of the individual allergen components and other molecules. In the component-resolved diagnosis of cat allergy, singleplex and multiplex specific immunoglobulin (Ig) E assays include use of the cat-specific major allergen, secretoglobin Fel d 1 (as a species-specific molecule), other allergen components (such as lipocalins Fel d 4, cross-reacting with other animal similar molecules, and Fel d 7, present in small quantities in natural extracts), and serum albumin Fel d 2 (related to the cat-pork syndrome). IgA Fel d 5 and IgM Fel d 6 are not available as allergen components in the current commercial IgE immunoassays, but they may impair the in vitro diagnostic evaluation of cat allergy because galactose-α1,3-galactose is an IgE-binding epitope of these native feline allergens. The benefits of molecular-based cat allergy diagnosis are continually evaluated, as the role of recombinant allergen components already known is detailed and new other molecules of interest may be discovered in the future.

IgE-Binding Monocytes Have an Enhanced Ability to Produce IL-8 (CXCL8) in Animals with Naturally Occurring Allergy.

IL-8 is a potent chemokine that recruits neutrophils and basophils to promote inflammation in many species. IL-8 is produced by many cell types, including monocytes. In this study, we report a novel role for IgE-binding monocytes, a rare peripheral immune cell type, to promote allergic inflammation through IL-8 production in a horse model of natural IgE-mediated allergy. We developed a mAb with confirmed specificity for both recombinant and native equine IL-8 for flow cytometric analysis. Equine IL-8 was produced by CD14+/MHC class II+/CD16- monocytes, including a subpopulation of IgE-binding monocytes, following stimulation with LPS. In addition, IgE cross-linking induced IL-8 production by both peripheral blood basophils and IgE-binding monocytes. IL-8 production was compared between healthy horses and those with a naturally occurring IgE-mediated skin allergy, Culicoides hypersensitivity. Allergic horses had significantly higher percentages of IL-8+ IgE-binding monocytes after IgE cross-linking. In contrast, frequencies of IL-8+ basophils after IgE cross-linking were similar in all horses, regardless of allergic disease, highlighting IgE-binding monocytes as a novel source of IL-8 during allergy. We concluded that IgE-binding monocytes from allergic individuals have an increased capacity for IL-8 production and likely contribute to the recruitment of innate immune cells during IgE-mediated allergy and promotion of inflammation during repeated allergen contact.

Decrease in CD38+ TH2A cell frequencies following immunotherapy with house dust mite tablet correlates with humoral responses.

In line with evidence for a role of pathogenic TH2A in seasonal allergies, we previously showed that individuals suffering from food allergy exhibited a decrease in circulating TH2A cells following multi-food immunotherapy. Herein, we aim to confirm the decline of TH2A cells in individuals undergoing house dust mite immunotherapy (HDM-AIT) and extend our observation to a new subset of CD38 expressing activated TH2A cells. The frequencies of TH2A and CD38+ TH2A cells were analysed by flow cytometry in blood cells from 182 Japanese HDM-allergic individuals included in a 1-year clinical trial assessing the efficacy of HDM tablets. Interrelationship between these cellular responses and humoral mite-specific IgE and IgG4 levels was further explored. A decrease in TH2A cells was observed in both active and placebo groups. Interestingly, CD38+ TH2A cell frequencies significantly decreased only in active groups. In younger individuals (16-30years), both TH2A and CD38+ TH2A cells were significantly reduced in active groups but not in the placebo group. Significant inverse correlations were observed in the course of HDM-AIT between changes in TH2A or CD38+ TH2A frequencies and IgG4 antibody levels. We confirm the value of monitoring TH2A cell frequencies in allergic individuals and extend this observation to perennial allergy to HDM. We highlight the interest of CD38 to better identify the subset of TH2A cell down-regulated by AIT. Finally, correlated cellular and humoral responses observed in immunoreactive individuals stress that coordinated pathways occur in the adaptive responses during AIT.

Structure-guided design of ultrapotent disruptive IgE inhibitors to rapidly terminate acute allergic reactions

Anaphylaxis represents one of the most severe and fatal forms of allergic reactions. Like most other allergies, it is caused by activation of basophils and mast cells by allergen-mediated cross-linking of IgE bound to its high-affinity receptor, FcεRI, on the cell surface. The systemic release of soluble mediators induces an inflammatory cascade, rapidly causing symptoms with peak severity in minutes to hours after allergen exposure. Primary treatment for anaphylaxis consists of immediate intramuscular administration of adrenaline. While adrenaline alleviates life-threatening symptoms of an anaphylactic reaction, there are currently no disease-modifying interventions available. We sought to develop potent and fast-acting IgE inhibitors with the potential to rapidly terminate acute allergic reactions. Using affinity maturation by yeast display and structure-guided molecular engineering, we generated 3 optimized disruptive IgE inhibitors based on designed ankyrin repeat proteins and assessed their ability to actively remove IgE from allergic effector cells invitro as well as invivo in mice. The engineered IgE inhibitors rapidly dissociate preformed IgE:FcεRI complexes, terminate IgE-mediated signaling in preactivated human blood basophils invitro, and shut down preinitiated allergic reactions and anaphylaxis in mice invivo. Fast-acting disruptive IgE inhibitors demonstrate the feasibility of developing kinetically optimized inhibitors for the treatment of anaphylaxis and the rapid desensitization of allergic individuals.