Explore the vast range of titles available.

For young children with peanut allergy, dietary avoidance is the current standard of care. We aimed to assess whether peanut oral immunotherapy can induce desensitisation (an increased allergic reaction threshold while on therapy) or remission (a state of non-responsiveness after discontinuation of immunotherapy) in this population. We did a randomised, double-blind, placebo-controlled study in five US academic medical centres. Eligible participants were children aged 12 to younger than 48 months who were reactive to 500 mg or less of peanut protein during a double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomly assigned by use of a computer, in a 2:1 allocation ratio, to receive peanut oral immunotherapy or placebo for 134 weeks (2000 mg peanut protein per day) followed by 26 weeks of avoidance, with participants and study staff and investigators masked to group treatment assignment. The primary outcome was desensitisation at the end of treatment (week 134), and remission after avoidance (week 160), as the key secondary outcome, were assessed by DBPCFC to 5000 mg in the intention-to-treat population. Safety and immunological parameters were assessed in the same population. This trial is registered on ClinicalTrials.gov, NCT03345160. Between Aug 13, 2013, and Oct 1, 2015, 146 children, with a median age of 39·3 months (IQR 30·8–44·7), were randomly assigned to receive peanut oral immunotherapy (96 participants) or placebo (50 participants). At week 134, 68 (71%, 95% CI 61–80) of 96 participants who received peanut oral immunotherapy compared with one (2%, 0·05–11) of 50 who received placebo met the primary outcome of desensitisation (risk difference [RD] 69%, 95% CI 59–79; p<0·0001). The median cumulative tolerated dose during the week 134 DBPCFC was 5005 mg (IQR 3755–5005) for peanut oral immunotherapy versus 5 mg (0–105) for placebo (p<0·0001). After avoidance, 20 (21%, 95% CI 13–30) of 96 participants receiving peanut oral immunotherapy compared with one (2%, 0·05–11) of 50 receiving placebo met remission criteria (RD 19%, 95% CI 10–28; p=0·0021). The median cumulative tolerated dose during the week 160 DBPCFC was 755 mg (IQR 0–2755) for peanut oral immunotherapy and 0 mg (0–55) for placebo (p<0·0001). A significant proportion of participants receiving peanut oral immunotherapy who passed the 5000 mg DBPCFC at week 134 could no longer tolerate 5000 mg at week 160 (p<0·001). The participant receiving placebo who was desensitised at week 134 also achieved remission at week 160. Compared with placebo, peanut oral immunotherapy decreased peanut-specific and Ara h2-specific IgE, skin prick test, and basophil activation, and increased peanut-specific and Ara h2-specific IgG4 at weeks 134 and 160. By use of multivariable regression analysis of participants receiving peanut oral immunotherapy, younger age and lower baseline peanut-specific IgE was predictive of remission. Most participants (98% with peanut oral immunotherapy vs 80% with placebo) had at least one oral immunotherapy dosing reaction, predominantly mild to moderate and occurring more frequently in participants receiving peanut oral immunotherapy. 35 oral immunotherapy dosing events with moderate symptoms were treated with epinephrine in 21 participants receiving peanut oral immunotherapy. In children with a peanut allergy, initiation of peanut oral immunotherapy before age 4 years was associated with an increase in both desensitisation and remission. Development of remission correlated with immunological biomarkers. The outcomes suggest a window of opportunity at a young age for intervention to induce remission of peanut allergy. National Institute of Allergy and Infectious Disease, Immune Tolerance Network.

Children 4 to 11 months of age who were at high risk for development of peanut allergy were assigned to consumption or avoidance of peanuts until 60 months of age. Peanut allergy was more than five times as likely to develop in children assigned to peanut avoidance. The prevalence of peanut allergy among children in Western countries has doubled in the past 10 years, reaching rates of 1.4 to 3.0%, 1 – 3 and peanut allergy is becoming apparent in Africa and Asia. 4 , 5 This allergy is the leading cause of anaphylaxis and death due to food allergy and imposes substantial psychosocial and economic burdens on patients and their families. 6 Peanut allergy develops early in life and is rarely outgrown. 7 – 9 Clinical practice guidelines from the United Kingdom in 1998 9 and from the United States in 2000 10 recommended the exclusion of allergenic foods from the diets of infants at . . .

A previous trial showed that early consumption of peanuts resulted in fewer cases of allergy than did avoidance. In a follow-up study, all participants avoided peanuts from 5 to 6 years of age; those who had eaten peanuts in early life retained the ability to do so. Peanut allergy is a common and potentially life-threatening food allergy for which prevention and treatment strategies are required. 1 – 5 The Learning Early about Peanut Allergy (LEAP) trial showed that among infants at high risk for allergy, the sustained consumption of peanut, beginning in the first 11 months of life, resulted in an 81% lower rate of peanut allergy at 60 months of age than the rate among children who avoided peanuts. 6 , 7 In a study of oral immunotherapy to hen’s egg white, although children achieved unresponsiveness to an oral food challenge with egg, the majority had a reversion to egg . . .

Background: Double-blind placebo-controlled food challenge (DBPCFC) is currently considered the gold standard for peanut allergy diagnosis. However, this procedure that requires the hospitalization of patients, mostly children, in specialized centers for oral exposure to allergens may cause severe reactions requiring emergency measures. Thus, a simpler and safer diagnosis procedure is needed. The aim of this study was to evaluate the diagnostic performance of a new set of in vitro blood tests for peanut allergy. Methods: The levels of IgE directed towards peanut extract and recombinant peanut allergens Ara h 1, Ara h 2, Ara h 3, Ara h 6, Ara h 7, and Ara h 8 were measured in 3 groups of patients enrolled at 2 independent centers: patients with proven peanut allergy (n = 166); pollen-sensitized subjects without peanut allergy (n = 61), and control subjects without allergic disease (n = 10). Results: Seventy-nine percent of the pollen-sensitized patients showed IgE binding to peanut, despite their tolerance to peanut. In contrast, combining the results of specific IgE to peanut extract and to recombinant Ara h 2 and Ara h 6 yielded a peanut allergy diagnosis with a 98% sensitivity and an 85% specificity at a positivity threshold of 0.10 kU/l. Use of a threshold of 0.23 kU/l for recombinant Ara h 2 increased specificity (96%) at the cost of sensitivity (93%). Conclusion: A simple blood test can be used to diagnose peanut allergy with a high level of precision. However, DBPCFC will remain useful for the few cases where immunological and clinical observations yield conflicting results.

Peanut Oral Immunotherapy (POIT) holds promise for remission of peanut allergy, though treatment is protracted and successful in only a subset of patients. Because the gut microbiome has been linked to food allergy, we sought to identify fecal predictors of POIT efficacy and mechanistic insights into treatment response. Here, we conducted a secondary analysis of the IMPACT randomized, double-blind, placebo-controlled POIT trial (NCT01867671), using longitudinal fecal samples from 90 children, and performed 16S rRNA sequencing, shotgun metagenomics, and untargeted metabolomics. Integrated multi-omics analyses revealed a relationship between gut microbiome metabolic capacity and treatment outcomes. Five fecal bile acids present prior to treatment initiation predicted POIT efficacy (AUC 0.71). Treatment failure was associated with a specific bile acid profile, enhanced amino acid utilization, and higher copy number of the ptpA gene encoding a bacterial hydrolase that cleaves tripeptides containing proline residues – a feature of immunogenic peanut Ara h 2 proteins. In vitro, peanut-supplemented fecal cultures of children for whom POIT failed to induce remission evidenced reduced Ara h 2 concentrations. Thus, distal gut microbiome metabolism appears to contribute to POIT failure. Peanut oral immunotherapy (POIT) can treat peanut allergy, but only a subset of patients achieve lasting remission. Here, the authors show that POIT efficacy is associated with the gut microbiome’s functional capacity, specifically bile and amino acid metabolism and protein degradation.

Oral immunotherapy (OIT) is an emerging treatment for food allergy. While desensitization is achieved in most subjects, many experience gastrointestinal symptoms and few develop eosinophilic gastrointestinal disease. It is unclear whether these subjects have subclinical gastrointestinal eosinophilia (GE) at baseline. We aimed to evaluate the presence of GE in subjects with food allergy before peanut OIT. We performed baseline esophagogastroduodenoscopies on 21 adults before undergoing peanut OIT. Subjects completed a detailed gastrointestinal symptom questionnaire. Endoscopic findings were assessed using the Eosinophilic Esophagitis (EoE) Endoscopic Reference Score (EREFS) and biopsies were obtained from the esophagus, gastric antrum, and duodenum. Esophageal biopsies were evaluated using the EoE Histologic Scoring System. Immunohistochemical staining for eosinophil peroxidase (EPX) was also performed. Hematoxylin and eosin and EPX stains of each biopsy were assessed for eosinophil density and EPX/mm was quantified using automated image analysis. All subjects were asymptomatic. Pre-existing esophageal eosinophilia (>5 eosinophils per high-power field [eos/hpf]) was present in five participants (24%), three (14%) of whom had >15 eos/hpf associated with mild endoscopic findings (edema, linear furrowing, or rings; median EREFS = 0, IQR 0-0.25). Some subjects also demonstrated basal cell hyperplasia, dilated intercellular spaces, and lamina propria fibrosis. Increased eosinophils were noted in the gastric antrum (>12 eos/hpf) or duodenum (>26 eos/hpf) in 9 subjects (43%). EPX/mm correlated strongly with eosinophil counts ( = 0.71, < 0.0001). Pre-existing GE is common in adults with IgE-mediated peanut allergy. Eosinophilic inflammation (EI) in these subjects may be accompanied by mild endoscopic and histologic findings. Longitudinal data collection during OIT is ongoing.

IntroductionThe predisposition to food allergy development and the induction of allergen-specific immune responses appears to be initiated early in infancy. Early exposure to food allergens, such as peanut and cashew nut, via human milk is likely important in initiating oral tolerance and reducing risk of food allergy development. This trial aims to determine if the risk of developing peanut and cashew nut allergy during infancy can be reduced by a high peanut and cashew nut maternal diet during lactation.Methods and analysisThis is a multisite, parallel, two-arm (1:1 allocation), single-blinded (outcome assessors, statistical analyst and investigators), randomised controlled trial. Target sample size is 4412 participants (2206 per group). Women (aged 18–50 years) with a singleton pregnancy, who are planning to breastfeed and do not have peanut and/or cashew nut allergies are eligible to participate. After obtaining written informed consent, participants are randomised to either a high peanut and cashew nut diet (at least 60 peanuts and 40 cashew nuts per week) or a low peanut and cashew nut diet (no more than 20 peanuts and 12 cashew nuts per week). Participants are asked to follow their allocated diet from birth to 6 months postnatal. Individual lactation consultant advice and support is provided as required. The study’s primary outcome is food challenge proven IgE-mediated peanut and/or cashew nut allergy during infancy (0–18 months). Key secondary outcomes include infant sensitisation to peanut and/or cashew nut. Analyses will be performed on an intention-to-treat basis according to a prespecified statistical analysis plan.Ethics and disseminationEthical approval has been granted from the Western Australian Child and Adolescent Health Service Human Research Ethics Committee (approval number RGS0000006685). Trial results will be presented at scientific conferences and published in peer-reviewed journals.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN ACTRN12624000134527)

Background Peanut allergy is an increasingly common health problem. Current treatment guidelines are based on strict avoidance. However, in the last few years, oral immunotherapy protocols have shown promising results yielding increased tolerance to peanut in allergic children. Adolescence is particularly at risk. Methods/Design We have designed a randomized, double-blind, placebo-controlled, multicenter study to investigate the efficacy and safety of peanut oral escalating immunotherapy in a 12- to 18–year-old population with proved allergy to peanut. Patients are selected when the threshold of peanut intake is over 100 mg and 2 cumulated g on the first double-blind, placebo-controlled oral food challenge (DBPCOFC). During the build-up placebo-controlled blinded phase, doses containing peanut or placebo will be administered by gradual up-dosing from 10 mg to 2 g with 2-weekly increments. After this first randomized phase, the desensitized participants will continue to intake native peanut in an unblinded process during 13 or 37 weeks following a second randomization. Adverse events are picked up and managed throughout the entire protocol. The main endpoint is the percentage of patients with negative DBPCOFC at the threshold of 2 g of cumulative peanut at the end of the build-up phase of 24 weeks. Secondary endpoints include: (1) desensitization 6 weeks and 6 months after the end of the maintenance phase; (2) adverse effects during the build-up phase; (3) immunological profile confirming peanut desensitization. Immunologic assays will be carried out at every DBPCOFC and at the middle of the build-up phase to evaluate the peanut immunologic profile modifications. Discussion This double-blind, placebo-controlled study will be, to our knowledge, the first evaluation of a peanut oral immunotherapy protocol in teenagers in the purpose to reduce severe reactions after unexpected intake and to improve quality of life. Trial registration ClinicalTrial.gov: NCT02046083 (23 January 2014).

Recent Australian and international legislation requires labeling of wines made by using the potentially allergenic food proteins casein, milk, egg white, or isinglass (fish-derived) where “there is a detectable residual processing aid.” We investigated whether wines fined using these proteins or non–grape-derived tannins (tree-nut derived) can provoke significant clinical allergic reactions (anaphylaxis) in patients with confirmed immunoglobulin E–mediated relevant food allergy. A double-blind, placebo-controlled trial was performed to determine whether allergic reactions followed consumption of Australian commercial wines fined using one or more of the legislation-targeted food proteins. In addition, allergenicity of a larger panel of these wines was evaluated by blood basophil activation. No anaphylaxis was induced by wine consumption. Three mild clinical reactions to protein-fined wine and two mild reactions to unfined wine occurred, but there was no statistically significant difference in reaction parameters between subject groups or between processing aids. No pattern of basophil activation correlated with wine type, processing aid, or subject group. Wines fined with egg white, isinglass, or non–grape-derived tannins present an extremely low risk of anaphylaxis to fish-, egg-, or peanut-allergic consumers. Although consumption of milk protein-fined wine did not induce anaphylaxis, there were insufficient subjects to determine statistically whether wines fined with milk proteins present a risk to the very rare milk-allergic consumers. In summary, the observed lack of anaphylaxis and basophil activation induced by wines made using the legislation-targeted food proteins according to good manufacturing practice suggests negligible residual food allergens in these wines.

Immunoglobulin E (IgE) antibodies play a central role in immune responses against helminth and protozoan parasites; however, they also contribute to allergies. IgE antibodies (and the B cells generating them) are rare and thus poorly characterized. Croote et al. performed single-cell RNA sequencing of peripheral blood B cells from patients with peanut allergies and delineated each cell's gene expression, splice variants, and antibody sequences (see the Perspective by Gould and Ramadani). Unlike other isotypes, circulating IgE B cells were mostly immature plasmablasts. Surprisingly, certain IgE antibodies manifested identical gene rearrangements in unrelated individuals. These IgE antibodies showed high affinity and unexpected cross-reactivity to peanut allergens. Science , this issue p. 1306 ; see also p. 1247 Single-cell sequencing of IgE B cells from allergic individuals reveals surprising insights. Immunoglobulin E (IgE) antibodies protect against helminth infections but can also cause life-threatening allergic reactions. Despite their role in human health, the cells that produce these antibodies are rarely observed and remain enigmatic. We isolated single IgE B cells from individuals with food allergies and used single-cell RNA sequencing to elucidate the gene expression and splicing patterns unique to these cells. We identified a surprising example of convergent evolution in which IgE antibodies underwent identical gene rearrangements in unrelated individuals. Through the acquisition of variable region mutations, these IgE antibodies gained high affinity and unexpected cross-reactivity to the clinically important peanut allergens Ara h 2 and Ara h 3. These findings provide insight into IgE B cell transcriptomics and enable biochemical dissection of this antibody class.