Peanut Anaphylaxis Research Articles

Analysis of Value-Based Costs of Undesignated School Stock Epinephrine Policies for Peanut Anaphylaxis

To determine if laws that allow undesignated school stock epinephrine autoinjectors are cost-effective by defining value and cost of different school strategies.Markov simulations of the Chicago Public Schools system were used over extended time horizons to model 2 school stock epinephrine autoinjector policies that provide access for students at risk for anaphylaxis at school. The dates of the data used in the analysis were September 2017 to June 2018 (the 2017–2018 school year).Researchers in this study compared the following 3 strategies: (1) no school epinephrine supply, in which the only devices available are personal autoinjectors provided by students with an allergic condition; (2) school undesignated supplemental epinephrine supply, in addition to student-supplied devices (supplemental model); and (3) school undesignated universal epinephrine supply, in which school-based devices supplant the need for student-supplied devices (universal model). Computer-based mathematical microsimulations (Markov simulations) were used to evaluate hypothetical cohorts of children with peanut allergy from kindergarten through high school graduation, with a continued horizon to age 80 years. The base-case model assumed a 10-fold reduced fatality risk with having undesignated stock epinephrine units available versus not having undesignated stock epinephrine units available. Costs of school stock epinephrine units available for acquisition by schools were evaluated from a societal perspective. Quality-adjusted life-years (QALYs) and total epinephrine acquisition expenses were calculated. These models were used because they can account for the annual costs and recurrent risks of peanut exposure and reactions.The cost was $107 816 (95% confidence interval [CI]: $107 382–$108 250) for no school undesignated epinephrine supply compared with $108 160 (95% CI: $107 725–$108 595) for the supplemental model and $100 397 (95% CI: $99 979–$100 815) for the universal model. When comparing supplemental model stock epinephrine to the strategy without undesignated devices, the incremental cost-effectiveness ratio was high at $268 811 per QALY in the base-case simulation. However, the cost of the supplemental model fell to <$100 000 per QALY when the annual undesignated epinephrine acquisition costs did not exceed $338 per school (compared with stock epinephrine unavailability). The universal model dominated all others and was associated with significant cost savings ($7419 per student at risk who would otherwise be prescribed an individual school epinephrine supply).Undesignated school stock epinephrine is cost-effective if device acquisition costs do not exceed $338 per school per year, and a universal model versus a supplemental model is associated with superior health and economic outcomes.Legislation to either permit or mandate school-based stock epinephrine programs has emerged to provide timely access to epinephrine for children, given that up to 8% of US children have food allergies and as many as 25% of first-time anaphylactic reactions occur in school. Currently, schools either have no designated stock epinephrine or supplemental epinephrine, where students are still asked to provide their own epinephrine autoinjectors. The authors argue that a universal model, in which all schools have stock epinephrine and do not require at-risk students to also provide autoinjectors, would achieve the desired health outcomes and is more cost-effective. This may reduce the cost burden on families and decrease the risk of further supply interruptions and shortages from pharmaceutical companies. However, although the universal model is cost-saving, there are important practical advantages to having students also carry their own designated individual epinephrine units because they would be available in close proximity daily, in transit to and from school (eg, on the school bus), on school field trips, and for after-school activities.

Anaphylaxie à l’arachide par voie inhalée, à propos de 3 cas

Paradoxically, some dispute surrounds the risk of anaphylaxis through inhalation of peanut fragments and the literature contains only rare reports. Herein we describe 3 cases of inhaled peanut anaphylaxis in patients with a strong allergic phenotype: 2 cases of adolescents coming into contact with peanuts in public places (cinema, train) on two occasions, and a third case in a child receiving peanut immune tolerance induction (ITI). Following published cases of inhaled peanut anaphylaxis and complaints by allergic patients, protective measures have been taken by airlines and in certain countries. However, it has recently been asserted that peanuts are not volatile and that the risk of reaction to inhalation is minimal at most! However, we believe it is important to protect patients with a strong phenotype and high anaphylactic risk and for whom social situations (travel, outings, etc.) present a potential danger. We feel that ITI should be proposed, coupled with therapeutic education, even though the limits of ITI were evident in our third patient.

Peanut allergy: Burden of illness.

Background: Peanut allergy affects 1% to 4.5% of children, with the potential for severe reactions. The peanut allergy burden impacts families, communities, and societies. Objective: To provide an update on the peanut allergy burden of illness and diagnostic pitfalls. Methods: A narrative review of the literature that described the role of food allergy testing for the evaluation of clinical allergy or eczema, consequences of peanut allergy diagnosis, quality of life, and emerging peanut immunotherapies. Results: Peanut allergy is considered persistent in the majority of those diagnosed with it; however, fatal anaphylaxis is rare. There is an absence of evidence to support food allergy screening in children with eczema, apart from those with immediate food reactions. Allergist-directed education may enhance the quality of life for patients and families living with peanut allergy. Appropriate pricing, availability, and use of epinephrine autoinjectors may reduce peanut allergy burden of illness. Peanut oral immunotherapy may decrease anxiety but, on balance, may cause more episodes of peanut anaphylaxis than it prevents. Conclusion: The personal, family, community, and societal burden of peanut allergy is significant but can be reduced by preventing overdiagnosis. Patient education should be anchored in the appropriate risk perspective. Longer-term data are needed to better understand how peanut immunotherapy products can be leveraged to improve patients' quality of life.

Analysis of Value-Based Costs of Undesignated School Stock Epinephrine Policies for Peanut Anaphylaxis

Children experiencing anaphylaxis at school may lack access to a personal epinephrine device, prompting recent legislation permitting undesignated (eg, non-student specific) stock epinephrine autoinjector units at school. However, epinephrine device costs vary, and the cost-effectiveness of undesignated school stock epinephrine is uncharacterized to date. To define value-based strategies for undesignated school stock epinephrine programs. Markov simulations of the Chicago Public Schools system were used over extended time horizons to model 2 school stock epinephrine autoinjector policies to provide access for at-risk students. The dates of the data used in the analysis were September 2017 to June 2018 (the 2017-2018 school year). This study compared the following 3 strategies: no school undesignated epinephrine supply, school undesignated supplemental epinephrine supply (supplemental model), and school undesignated universal epinephrine supply (universal model). The base-case model assumed a 10-fold reduced fatality risk with having undesignated stock epinephrine units available vs not having undesignated stock epinephrine units available. Costs of school stock epinephrine units available for acquisition by schools were evaluated from a societal perspective. Quality-adjusted life-years (QALYs) and total epinephrine acquisition expenses were calculated. Based on Markov simulations of the Chicago Public Schools system (371 382 students), the cost was $107 816 (95% CI, $107 382-$108 250) for no school undesignated epinephrine supply compared with $108 160 (95% CI, $107 725-$108 595) for the supplemental model and $100 397 (95% CI, $99 979-$100 815) for the universal model. Undesignated stock epinephrine improved outcomes, with 26.869 (95% CI, 26.841-26.897) QALYs accrued as the model concluded compared with 26.867 (95% CI, 26.839-26.896) QALYs for the strategy without undesignated stock epinephrine. When comparing supplemental model stock epinephrine to the strategy without undesignated devices, the incremental cost-effectiveness ratio was high at $268 811 per QALY in the base-case simulation. However, the cost of the supplemental model fell below $100 000 per QALY when the annual undesignated epinephrine acquisition costs did not exceed $338 per school (compared with stock epinephrine unavailability). The universal model dominated all others and was associated with significant cost savings ($7419 per student at risk who would otherwise be prescribed an individual school epinephrine supply). Undesignated school stock epinephrine is cost-effective at device acquisition costs not exceeding $338 per school per year, although a universal model vs a supplemental model is associated with superior health and economic outcomes.

Correlation of negative skin-prick test results for tree nuts and successful tree nut challenges among children with peanut allergy.

Background: Children with peanut allergy are regularly instructed to avoid all tree nuts. However, children with peanut allergy are likely not allergic to all tree nuts. Objective: In our cohort of patients with peanut anaphylaxis and who underwent oral immunotherapy, we sought to determine the correlation of skin-prick testing (SPT) results for tree nuts and the likelihood of successfully passing a tree nut challenge. Methods: SPT was performed for peanut and tree nuts (macadamia, pine nut, coconut, hazelnut, brazil nut, cashew, pecan, walnut, pistachio, almond) in 27 patients with known peanut allergy. The probability of a negative SPT result (wheal < 3 mm) for each nut was determined. Results: All the patients demonstrated positive results in peanut allergy diagnostics in SPT, component testing, or food challenge. Only 15.4% of the patients had a positive SPT result to peanut alone. Macadamia, pine nut, and coconut SPT had a probability of negative SPT results of 0.97, 0.97, and 0.91, respectively. The odds ratio for this group having a negative SPT was 46.22. For hazelnut, brazil nut, and cashew, the probability of a negative SPT result was 0.81, 0.77, and 0.73, respectively. Pecan, walnut, and pistachio had odds ratios of 0.68, 0.68, and 0.64, respectively. All the patients with macadamia, pine nut, and coconut negative SPT results subsequently passed 9-g food challenges without oral immunotherapy. Conclusion: Despite current recommendations to avoid all tree nuts for patients with peanut allergy, the majority of patients with peanut allergy had negative SPTs and food challenges to certain tree nuts, especially macadamia, pine nut, and coconut. This pattern was seen despite most patients having multiple nut sensitizations.

PREDICTIVE DECLINE IN PEANUT SKIN TEST AND RAST AMONG PEANUT-ALLERGIC CHILDREN UNDERGOING HIGH-DOSE ORAL IMMUNOTHERAPY

Introduction Peanut immunotherapy remains a limited form of treatment for peanut allergic children. Limitations primarily stem from small study sizes, significant adverse events, unclear long-term immunological outcomes and the inability to reach tolerance. In our cohort of peanut anaphylaxis patients undergoing tolerance induction oral immunotherapy, we sought to determine the rate of decline in peanut skin prick testing (SPT) and RAST results following one year of high-dose, weekly peanut immunotherapy. Methods Extensive RAST and SPT to peanut was performed in addition to other diagnostic markers. Fifty-one patients underwent sequential food challenges to non-allergic nuts followed by desensitization of sensitized or anaphylactic tree nuts culminating with peanut desensitization. All patients passed a 10g peanut protein challenge. Patients transitioned over 4 months to pass a 30g peanut protein challenge. Patients sustained a weekly 30g peanut protein dose for one year. During any given week, patients were free to eat products with Results All patients demonstrated positive peanut allergy diagnostics in SPT, component testing and RAST before treatment; post-treatment a reduction was observed in this cohort. The rate of reduction was greatest for patients whose post-SPT value was in the lowest quartile (reduced to 22.2% of pre-SPT value which corresponded to an average drop from 7.5-2.0mm). Conclusions Peanut-specific RAST and SPT are reproducible, temporal markers when following patient response to immunotherapy. Peanut immunotherapy is effective in reducing SPT and RAST specific peanut values corroborated with intermittent, high-dose peanut protein exposure.

Feasibility of desensitizing children highly allergic to peanut by high-dose oral immunotherapy.

There are limited data on the feasibility, efficacy and safety of high-dose oral immunotherapy (OIT) in children highly allergic to peanuts. In children highly allergic to peanut, we primarily aimed to determine the feasibility of reaching the maximum maintenance dose (MMD) of 5000mg peanut protein or, alternatively, a lower individual maintenance dose (IMD), by OIT up-dosing. Secondarily, we aimed to identify adverse events (AEs) and determine factors associated with reaching a maintenance dose. The TAKE-AWAY peanut OIT trial enrolled 77 children 5-15years old, with a positive oral peanut challenge. Fifty-seven were randomized to OIT with biweekly dose step-up until reaching MMD or IMD and 20 to observation only. Demographic and biological characteristics, AEs, medication and protocol deviations were explored for associations with reaching maintenance dose. All children had anaphylaxis defined by objective symptoms in minimum two organ systems during baseline challenge. The MMD was reached by 21.1%, while 54.4% reached an IMD of median (minimum, maximum) 2700 (250, 4000) mg peanut protein, whereas 24.5% discontinued OIT. During up-dosing, 19.4% experienced anaphylaxis. Not reaching the MMD was caused by distaste for peanuts (66.7%), unacceptable AEs (26.7%) and social reasons (6.7%). Increased peanut s-IgG4 /s-IgE ratio (OR [95% CI]: 1.02 [1.00, 1.04]) was associated with reaching MMD. Although 75.5% of children with peanut anaphylaxis reached a maintenance dose of 0.25-5g, only 21.1% reached the MMD. Distaste for peanuts and AEs, including high risk of anaphylaxis, limited the feasibility of reaching MMD.

Low-dose oral immunotherapy for children with anaphylactic peanut allergy in Japan.

Oral immunotherapy (OIT) is a promising treatment for persons with allergy; however, it can also cause adverse allergic reactions. In this study, we investigated the efficacy of low-dose OIT for anaphylactic peanut allergy. Twenty-four children (median age, 9.6years) with anaphylaxis to peanuts were hospitalized for 5days and then gradually fed increasing amounts of peanut powder up to 133mg/day. One year later, they underwent an oral food challenge after 2weeks of peanut avoidance. Those who were asymptomatic after ingesting 795mg of peanut protein were defined as having achieved sustained unresponsiveness. We measured peanut- and Ara h2-specific immunoglobulin (Ig) E, IgG, and IgG4 levels at 0, 1, 3, 6, and 12months in the OIT group and at 0 and 12months in the control group. At baseline, all children in the OIT group and 8 in the control group had a history of anaphylaxis. The median peanut-/Ara h2-specific IgE levels in the OIT and control groups were 55.4/48.6 and 58.2/38.1kUa/L, respectively. One year later, 8 (33.3%) children in the OIT group exhibited sustained unresponsiveness, while none in the control group did. In the OIT group, the median peanut-specific IgE levels significantly increased to 194.0kUa/L, after 1month and then significantly decreased to 57.5kUa/L at 12months. Meanwhile, the median peanut- and Ara h2-specific IgG and IgG4 levels increased significantly after 1month. Low-dose OIT induces immunological changes and has the capability of achieving sustained unresponsiveness in children with peanut anaphylaxis.

Oral Immunotherapy in Japanese Children with Anaphylactic Peanut Allergy

Background: Reports on oral immunotherapy (OIT) for anaphylactic food allergy are lacking. We investigated the efficacy and safety of peanut OIT for anaphylactic patients. Methods: We enrolled 22 peanut anaphylactic patients who underwent OIT between 2011 and 2013, all of whom demonstrated anaphylaxis during a baseline double-blind, placebo-controlled food challenge. After starting in-hospital OIT, participants gradually increased ingestion to 795 mg of peanut protein per day at home and then took a maintenance dose (795 mg) daily. After 3 asymptomatic months, participants underwent an oral food challenge (OFC) of 795 mg after 2 weeks of peanut avoidance to confirm sustained unresponsiveness. The historical control group consisted of 11 patients with anaphylaxis by OFC and underwent the second OFC after 2 years. Results: All patients (22/22) achieved desensitization by 8 months after starting OIT and completed the protocol within 2 years. Two years later, 15/22 patients (68.1%) in the OIT group achieved sustained unresponsiveness, whereas only 2 (18.1%) in the control group passed the second OFC. After 2 years, the median peanut-specific IgE had significantly decreased (from 38.5 to 12.4 kUA/L) in the OIT group, but not in the control group. Median peanut- and Ara h 2-specific IgG4 in the OIT group had significantly increased from baseline after 1 month. The adverse reaction rate per ingestion was 43% in hospital and 5% at home. Three patients received adrenaline at the hospital and 2 at home. Conclusions: These data suggest that for patients with peanut anaphylaxis, OIT can increase the threshold and support achieving sustained unresponsiveness with relative safety.

P331 Risks of new guidelines to prevent peanut allergy; peanut anaphylaxis in a 6-month-old

P331 Risks of new guidelines to prevent peanut allergy; peanut anaphylaxis in a 6-month-old

Lifelong memory responses perpetuate humoral TH2 immunity and anaphylaxis in food allergy

A number of food allergies (eg, fish, shellfish, and nuts) are lifelong, without any disease-transforming therapies, and unclear in their underlying immunology. Clinical manifestations of food allergy are largely mediated by IgE. Although persistent IgE titers have been attributed conventionally to long-lived IgE+ plasma cells (PCs), this has not been directly and comprehensively tested. We sought to evaluate mechanisms underlying persistent IgE and allergic responses to food allergens. We used a model of peanut allergy and anaphylaxis, various knockout mice, adoptive transfer experiments, and invitro assays to identify mechanisms underlying persistent IgE humoral immunity over almost the entire lifespan of the mouse (18-20months). Contrary to conventional paradigms, our data show that clinically relevant lifelong IgE titers are not sustained by long-lived IgE+ PCs. Instead, lifelong reactivity is conferred by allergen-specific long-lived memory B cells that replenish the IgE+ PC compartment. B-cell reactivation requires allergen re-exposure and IL-4 production by CD4 T cells. We define the half-lives of antigen-specific germinal centers (23.3days), IgE+ and IgG1+ PCs (60 and 234.4 days, respectively), and clinically relevant cell-bound IgE (67.3days). These findings can explain lifelong food allergies observed in human subjects as the consequence of allergen exposures that recurrently activate memory B cells and identify these as a therapeutic target with disease-transforming potential.

Berberine as a chemical and pharmacokinetic marker of the butanol-extracted Food Allergy Herbal Formula-2

RationaleFood Allergy Herbal Formula-2 (FAHF-2) provided protection against peanut anaphylaxis in a murine model and induced beneficial immune-modulation in humans. Butanol-refined FAHF-2, B-FAHF-2, retained safety and efficacy in the peanut allergic murine model at only 1/5 of FAHF-2 dosage. One compound, berberine, was isolated and identified in vitro as a bioactive component present in FAHF-2 and B-FAHF-2. The aim of this study was to investigate berberine as a chemical and pharmacokinetic marker of B-FAHF-2. MethodsThe consistency of constituents between B-FAHF-2 and FAHF-2 was tested. Peanut allergic C3H/HeJ mice were orally administered with 1mg of berberine or B-FAHF-2 containing an equivalent amount of berberine, and the ability to protect against peanut anaphylaxis and pharmacokinetic parameters were determined. Human intestinal epithelial cells (Caco-2) were cultured with berberine with or without the nine individual herbal constituents in B-FAHF-2, and the absorbed berberine levels were determined. ResultsBerberine is one of the major components in B-FAHF-2 and FAHF-2 formula. In a peanut allergic mouse model, B-FAHF-2, but not berberine, protected mice from anaphylaxis reactions. Pharmacokinetic profiles showed that the Cmax of B-FAHF-2 fed mice was 289.30±185.40ng/mL; whereas berberine alone showed very low bioavailability with Cmax value of 35.13±47.90ng/mL. Caco-2 cells influx assay showed that 7 of 9 herbal constituents in B-FAHF-2 increased berberine absorption at rates ranging from 18 to 205%. ConclusionsB-FAHF-2 remarkably increased the bioavailability of berberine. Berberine can be used as chemical and pharmacokinetic marker of B-FAHF-2. Other herbal components in B-FAHF-2 may facilitate the absorption of berberine.

P270 Diagnostic associations of Ara H8 and Ara H9 components in peanut-allergic children

Component resolved diagnostics are increasingly utilized in the diagnosis of peanut allergy. Ara h2 is associated with severity of peanut allergy. Other peanut components are poorly understood in the clinical setting. In our cohort of peanut anaphylaxis patients undergoing oral immunotherapy (OIT), we sought to determine the pre treatment correlation of Ara h8 and Ara h9 with standardized peanut RAST and other peanut components.

O030 Correlating rast, component levels, skin testing, and epinephrine requirements in patients with anaphylaxis to peanut

Peanut allergen exposure resulting in epinephrine-requiring anaphylaxis is a major health concern. Peanut IgE and components are increasingly ordered, yet research-guided directives regarding clinical correlation and utilization of peanut component diagnostic testing is lacking. In patients with WAO Grade II or higher peanut anaphylaxis, we investigated the correlation between serum-specific peanut IgE (sIgE), component levels, skin prick testing (SPT) and number of anaphylactic episodes and epinephrine use.

Clinical Significance of Component Allergens in Fagales Pollen-Sensitized Peanut Allergy in Korea.

PurposeClinical features of peanut allergy can range from localized to systemic reactions. Because peanut and birch pollen have cross-reactivity, peanut can lead to localized allergic reaction in Fagales pollen-sensitized oral allergy syndrome (OAS) patients without peanut sensitization per se. The purpose of this study was to discriminate true peanut food allergy from cross-reactive hypersensitivity in birch-sensitized peanut allergy.MethodsBirch-sensitized (n=81) and peanut anaphylaxis patients (n=12) were enrolled. Peanut-related allergic reactions and sensitization profiles were examined. Specific IgE to Fagales tree pollens (birch, oak), peanut, and their component allergens (Bet v 1, Bet v 2, Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Ara h 9) were evaluated. Based on these specific IgEs and clinical features, the patients were classified into 4 groups: group 1 (Fagales pollen allergy without OAS), group 2 (Fagales pollen allergy with OAS), group 3 (OAS with peanut anaphylaxis), and group 4 (peanut anaphylaxis).ResultsAfter peanut consumption, one-third of OAS patients experienced oral symptoms not associated with peanut sensitization. Ara h 1 or Ara h 2 was positive in peanut anaphylaxis patients, whereas Ara h 8 was positive in OAS patients. There were 4 patients with both peanut anaphylaxis and OAS (group 3). Both Ara h 2 and Ara h 8 were positive in these patients. Foods associated with OAS in Korea showed unique patterns compared to Westernized countries.ConclusionsAra h 2 and Ara h 8 may be important component allergens for discriminating peanut allergy.

Peanut allergy: a mouse model comparison (HYP4P.309)

Abstract Peanut induced anaphylaxis often results in a bi-phasic response, associated with a second anaphylaxis once current treatment interventions have been removed. Previous reports have suggested that this response is associated with elevated levels of platelet activating factor. Our studies have focused on refining the murine model of peanut anaphylaxis with the hypothesis that we can generate a model that recapitulates the anaphylactic response to peanuts. We used BALB/c and C3H/HeJ mice (N=20 for each study) mice were sensitized weekly for 6 weeks with crude peanut extract in cholera toxin. Mice were then grouped for crude peanut extract or saline challenge by intra-peritoneal injection. In all mice, temperatures and clinical scores were accessed both early post injection as well as 2 hours later. Serum, lungs, spleen, and liver were stored from all animals for future studies. The BALB/c strain had a mean temperature change from baseline of 0.2 C⁰ for the controls initial post IP versus the 1.89 C⁰ for the challenged mice. The C3H/HeJ strain had a mean temperature change from baseline of 0.1 C⁰ for the controls at the initial post IP versus the 4.2 C⁰ change for the challenged mice. Similar results were noted at the 2 hour mark with the C3H/HeJ strain with the greater temperature change. Both strains had notable changes in clinical scores between the control and challenge groups. This was more pronounced in the C3H/HeJ mice both clinically and by temperature measurement.

Reversal of peanut anaphylaxis by retinoic acid-differentiated dendritic cell immunotherapy. IL-27-dependent induction of Foxp3- non-Tr1 regulatory T cells (VAC4P.1100)

Abstract Background. Semi-mature IL-10-induced DC (DC10) induce human or mouse effector Th2 cells (Teff) to differentiate into Foxp3+ Treg and thereby induce asthma tolerance. Retinoic acid (RA) and TGFβ-induced gut DC similarly induce tolerance to gut contents via Foxp3+ Treg, while immature hDC-10 induce IL-10-dependent Foxp3- Tr1 cells. Methods. We assessed the abilities of mature RA-induced DC to reverse anaphylaxis sensitivity, characterizing LPS-matured DC-RA and their tolerogenic activities in mouse models of OVA and peanut systemic anaphylaxis. Results. Mature DC-RA strongly expressed CD103 (αE integrin), MHCII, co-stimulatory markers, PDL1 &amp; -L2, ICOSL, TGFβ, IL-27 and the RA-metabolizing enzyme Aldh1A2. They induced Th2 cells to convert into CD25+LAG3+CD49b-IL-10-Foxp3- Treg in an IL-10-independent, IL-27-dependent fashion, although IL-27 was dispensable for Th2 suppression by DC-RA. Wild-type, but not IL-27-/- DC-RA therapy reversed systemic anaphylaxis, including clinical scores, diarrhea, mast cell activation and Th2 responses, and lowered serum allergen-specific IgE and IgG1 levels. Conclusions. Allergen-presenting DC-RA induce food allergen tolerance by activating CD25+Foxp3-, non-Tr1 responses in an IL-27-dependent fashion. This data indicates that, like DC10, DC-RA can also be used for allergic disease immunotherapy, but that these two populations of DCreg induce distinct Treg responses, and this potentially provides us with important options DCreg immunotherapy

Comprehensive metabolomics identifies the alarmin uric acid as a critical signal for the induction of peanut allergy.

Food allergy, in particular peanut allergy, is a growing concern in Western countries. The prevalence of allergy to peanut, which currently stands at 1.4%, nearly tripled between 1997 and 2008. Allergic sensitization is a particularly difficult process to study as it is clinically silent. We sought to identify key pathways and mediators critically involved in the induction of allergic sensitization to peanut. Comprehensive metabolomics analysis with liquid chromatography-mass spectrometry was used to detect metabolite changes in mice (C57BL/6) undergoing sensitization. Loss-of-function and gain-of-function studies were performed in mice subjected to two models of peanut sensitization and anaphylaxis that involved either oral or epicutaneous sensitization. Flow cytometric analyses on dendritic cells (DCs) in vitro and in vivo were used to investigate the mechanisms of immune activation. Elevated levels of uric acid (UA) were detected in mice undergoing sensitization as well as in peanut-allergic children who were not challenged with peanut. In mice, the depletion of UA during sensitization prevented the development of peanut-specific immunoglobulins IgE and IgG1 as well as anaphylaxis while exogenous delivery of UA crystals (monosodium urate, MSU) restored the allergic phenotype. Monosodium urate enhanced CD86 and OX40L expression on DCs, independent of Toll-like receptors 2 and 4, the NLRP3 inflammasome, and IL-1β, via a PI3K signaling pathway. Overproduction of the UA alarmin in the local microenvironment plays a critical role in the induction of peanut-allergic sensitization, likely due to its ability to activate DCs. These finding suggest that cellular damage or tissue injury may be an essential requisite for the development of allergic sensitization to foods.

Safety, Clinical and Immunologic Efficacy of a Chinese Herbal Medicine (FAHF-2) for Food Allergy

Background FAHF-2 is a 9-herb formula based on Traditional Chinese Medicine that blocks peanut anaphylaxis in a murine model. In Phase I studies, FAHF-2 was found to be safe, and well tolerated.

Specific epicutaneous immunotherapy prevents sensitization to new allergens in a murine model

Allergy to cow's milk increases the risk of sensitization to other foods in young children. We sought to evaluate the effect of early epicutaneous immunotherapy (EPIT) on further sensitization to peanut or house dust mite (HDM) in a murine model of sensitization to cow's milk. BALB/c mice orally sensitized to milk were epicutaneously treated with a Viaskin patch (DBV Technologies) loaded with milk proteins for 8 weeks. Mice were then sensitized to peanut or HDM. After sensitization to peanut, mice were exposed to a peanut regimen known to induce eosinophilic esophageal inflammation. After sensitization to HDM, mice were challenged with aerosols to HDM, and airway hyperresponsiveness was evaluated by using plethysmography. Humoral response was also analyzed. The role of regulatory T (Treg) cells was evaluated by adoptively transferring Treg cells from milk EPIT-treated mice to naive mice before sensitization to peanut. Protection against anaphylaxis was also investigated. Methylation of the promoter region of transcription factors was analyzed by using PCR assays. In milk-sensitized mice specific EPIT prevented further sensitization to peanut or HDM. EPIT significantly modified the humoral response, reduced TH2 cytokine levels, decreased eosinophilic esophageal infiltration, and suppressed airway hyperresponsiveness. The protective effect was sustained over 2 months. Moreover, the adoptive transfer of milk EPIT Treg cells completely prevented sensitization to peanut and peanut-induced anaphylaxis. Milk EPIT enhanced methylation of the GATA-3 promoter region. Our results showed that EPIT influences the natural history of allergy and reduces the risk of further sensitization through a Treg cell-dependent mechanism.