Induction of Peanut Allergy Through Inhalation of Peanut in Mice.
Peanut (PN) allergy is a common life-threatening disease; however, our knowledge on the immunological mechanisms remains limited. Here, we describe the first mouse model of inhalation-driven peanut allergy. We administered PN flour intranasally to naïve wild-type mice twice a week for 4 weeks, followed by intraperitoneal challenge with PN extract. Exposure of mice to PN flour sensitized them without addition of adjuvants, and mice developed PN-specific IgE, IgG1, and IgG2a. After challenge, mice displayed lower body temperature and other clinical signs of anaphylaxis. This inhalation model is an ideal system to allow for future examination of immunological mechanisms critical for the development of PN allergy.
Accurate prediction of peanut allergy in one-third of adults using a validated Ara h 2 cutoff.
Background: The diagnostic value of peanut components is extensively studied in children, but to a lesser extent in adults with suspected peanut allergy. The use of peanut components in daily practice may reduce the need for double-blind placebo-controlled food challenges (DBPCFCs), however validation studies are currently lacking. Objective: To 1) evaluate the diagnostic value of (combined) peanut components and 2) validate a previous found Ara h 2 cutoff level with 100% positive predictive value (PPV) in adults with suspected peanut allergy. Methods: Adults who underwent a peanut DBPCFC were included: 84 patients from a previous study (2002 to 2012) and 70 new patients (2012 to 2019). Specific IgE to peanut extract, Ara h 1, 2, 3, 6 and 8 was measured using ImmunoCAP. Diagnostic value was assessed with an area under the curve (AUC) analysis. Results: In total, 95 (62%) patients were peanut allergic. sIgE to Ara h 2 and Ara h 6 were the best predictors with an AUC (95% CI) of 0.85 (0.79-0.91) and 0.85 (0.79-0.92), respectively. The Ara h 2 cutoff level with 100% PPV (≥1.75 kUA/L) was validated in the 70 new patients. Thirty percent of all included patients could be classified correctly as peanut allergic using this validated cutoff level. Conclusion: sIgE to Ara h 2 and Ara h 6 have equally high discriminative ability. Peanut allergy can be predicted accurately in one-third of adults using a validated cutoff level of sIgE to Ara h 2.
Irradiated Tree Nut Flours for Use in Oral Immunotherapy.
Background: Tree nut allergies affect an estimated 1% of the United States population and is lifelong in 90% of allergic individuals. Oral immunotherapy (OIT) for food allergies is an effective method to induce desensitization in a majority of participants in trials of peanut, egg, and milk OIT. Limited trials using tree nut OIT have been reported, possibly due to the lack of standardized drug products. Objective: Food products used in OIT are considered drugs by the FDA since they are intended to modulate the individuals' immune responses to the food allergens. As such, OIT drug products must meet FDA standards for acceptable levels of microbes and undergo testing for allergenic proteins. We aimed to determine the suitability of walnut, cashew, hazelnut, and almond flours for use in OIT trials. Methods: We employed gamma irradiation on commercially available walnut, cashew, hazelnut, and almond flours and tested their levels of microbial contamination, total protein and allergen content, along with stability of these parameters over time. Results: Our results demonstrate that irradiation of tree nut flours greatly diminishes the levels of total aerobic bacteria, mold, yeast, E. coli, and salmonella, while there are no substantial changes in total protein or allergen content. Importantly, the microbial levels, protein, and allergen content remained stable over a 24 month period. Conclusion: Irradiation of tree nut flours is a safe and effective method of processing to allow tree nut products to meet the FDA standards for OIT drug products.
The importance of the 2S albumins for allergenicity and cross-reactivity of peanuts, tree nuts and sesame seeds.
Allergies to peanuts, tree nuts, and sesame seeds are among the most important food related causes of anaphylaxis. Important clinical questions include: why is there a variable occurrence of co-allergy among these foods and is this immunologically mediated? Clinical and immunological data summarized here suggest an immunologic basis for these co-allergies based on similarities among the 2S-albumins. Data from component resolved diagnostics have highlighted the relationship between IgE binding to these allergens and the presence of IgE-mediated food allergy. Furthermore, in vitro and in vivo experiments provide strong evidence that the 2S albumins are the most important allergens in peanuts for inducing an allergic effector response. Although the 2S albumins are diverse, they have a common disulfide linked core with similar physicochemical properties that make them prime candidates to explain much of the observed co-allergy among peanuts, tree nuts and sesame seeds. The well-established frequency of cashew and pistachio nut co-allergy (64-100%) highlights how the structural similarities among their 2S albumins may account for observed clinical cross-reactivity. A complete understanding of the physicochemical properties of the 2S albumins in peanuts, tree nuts and sesame seeds will enhance our ability to diagnose, treat and ultimately prevent these allergies.
Practical challenges and considerations for early introduction of potential food allergens for prevention of food allergy.
Recent randomized controlled trials aimed at the prevention of food allergy have led to sweeping changes in food allergy prevention guidelines. Emphasis is now on the introduction of potential food allergens, particularly peanut and egg, rather than avoidance. Though guidelines recommend against delaying introduction of other potential allergens there remains little or no evidence of the benefit of their early introduction. Parents and physicians alike report a need for greater guidance and resources on early potential allergen introduction in the complementary feeding period. A thorough understanding of early introduction literature, current prevention guidelines, and infant nutrition will empower physicians to address patient needs and concerns both when advice is established as effective and where uncertainty remains. We discuss the state of the science, compare recommendations between guidelines, and provide practical options to introduce allergenic foods, alongside other complementary foods, within the first year of life. We include a review of the available literature, including review and suggestions of potential doses of food allergens, and the first published comparison of commercially available products and home-made early introduction foods to help clinicians support their patients. We address the nutritional, dietary and practical considerations of introducing food allergens in the first year of life, while adhering to infant feeding guidelines. Finally, given the limitations of existing guidelines, we review the need for shared decision-making (SDM) between physicians and parents regarding early allergen introduction.
Emerging Therapies for Peanut Allergy.
Peanut allergy (PA) is a food allergy that causes an IgE-mediated type I hypersensitivity reaction. PA has become an increasing public health burden, with 2% of American children reported to have this condition in 2010. Current guidelines recommend allergen avoidance, patient education, and administration of H1 antihistamines, β2-agonists, or epinephrine based on the severity of reaction. In this review article, emerging therapies for PA are evaluated for their potential role in treating PA. Oral, epicutaneous, and sublingual immunotherapies have completed clinical trials with promising efficacy. In particular, Palforzia (AR101) is an oral immunotherapy that received Food and Drug Administration (FDA)-approval in January 2020 and Viaskin Peanut is an epicutaneous immunotherapy with an anticipated FDA decision date by August 5, 2020. Furthermore, adjuvant combinations with either probiotics or anti-IgE receptor antagonists have shown an improved efficacy and safety profile compared to oral immunotherapy alone. However, immunotherapy-induced adverse reaction rates are high due to the risks associated with intentional allergen exposure. These results suggest that peanut immunotherapy has a promising role in the treatment of PA, although further studies are needed before its incorporation into standard of care.
Infant Allergy Testing and Food Allergy Diagnoses Before and After Guidelines for Early Peanut Introduction.
Background: A landmark 2015 trial on early exposure to peanuts led to expert recommendations for screening and early peanut introduction in high-risk (severe eczema and/or egg allergy) infants, but the impact of this paradigm shift on allergy testing and diagnosis is unknown. Objective: We assessed the effects of the Learning Early About Peanut Allergy (LEAP) trial and guideline publications on allergy testing and food allergy diagnoses in infants. Methods: In this retrospective cohort study, de-identified administrative health claims from a commercial and Medicare advantage claims database were used. Infants with at least one year of continuous coverage were selected using newborn codes for birth hospitalizations from January 2010 to June 2018. Interrupted time series models were used to compare the prevalence of allergy testing before and after LEAP publication in February 2015 and formal guideline publication in January 2017. Results: For 487,533 included infants, allergy testing increased after LEAP (risk ratio [RR]: 1.11 [95% CI, 1.07-1.15]) and guidelines (1.21 [1.18-1.23]). This increase of testing was also seen in infants not considered high-risk, both after LEAP (1.12 [1.08-1.17]) and guidelines (1.20 [1.16, 1.23]). For first-time allergy tests, post-guideline median number of allergens tested was 9 for serum tests and 10 for skin tests. Post-guidelines there was a significant increase in diagnosis of peanut (RR: 1.08 [1.00, 1.16]), egg (1.12 [1.05, 1.20]), and other food allergies (excluding milk) (1.22 [1.14, 1.31]). Conclusion: Allergy testing has increased, including in non-high-risk infants. Multi-allergen testing may be contributing to an increase in the diagnosis of other food allergies.
Peanut Allergy–No Longer a Life Sentence.
In this review we provide an overview on the latest knowledge in the prevention and active management of peanut allergy. The rise in incidence of food allergy has generated new challenges in the management of affected individuals. Strategies to counteract the increase in prevalence of peanut allergy can be considered as a pyramid, beginning with primary prevention of those at risk through earlier introduction of peanut into the infant diet, to secondary prevention of peanut-sensitised children through improvements in the correct diagnosis of peanut allergy and finally to the treatment of children with proven peanut allergy. CONCLUSION: With the paradigm shift towards an active management, peanut allergy should no longer be seen as a life sentence.
Effect of hot air and infrared roasting on hazelnut allergenicity.
Roasting is known to affect the protein profile and allergenicity of hazelnuts (Corylus avellana cv TGL). The aim of the study was to investigate whether roasting techniques based on different heat transfer methods (hot air and infrared), differently affect the protein solubility and the IgE-binding capacities of both the soluble and insoluble hazelnut protein fractions. The immune-reactivity of the Cor a 9, Cor a 11 and Cor a 14 allergens resulted to be stable after roasting at 140 °C, for both types of treatment, while roasting at 170 °C caused a reduction in IgE-binding, which was particularly noticeable after infrared processing, that led to an almost complete disappearance of allergenicity. Microscopical analyses showed that roasting caused cytoplasmic network disruption, with a loss of lipid compartmentalization, as well as an alteration of the structure of the protein bodies and of the cell wall organization.
Replacing white rice bars with peanuts as snacks in the habitual diet improves metabolic syndrome risk among Chinese adults: a randomized controlled trial.
Background: Observational studies have suggested that intake of nuts is associated with lower risk of cardiometabolic diseases, whereas refined grain consumption has been linked to higher risk. Little is known about whether substituting white rice, a refined grain, with nuts may confer benefit among adults at high risk of cardiometabolic diseases. Objectives: We aimed to evaluate isocaloric substitution of peanuts for white rice bars as snacks on changes in fasting glucose, lipid profile, body weight, as well as changes in metabolic syndrome (MetS) status among participants with MetS or at risk of MetS. Methods: This parallel-arm randomized controlled trial included 224 participants either with MetS (according to the International Diabetes Federation criteria for Chinese adults, n = 163) or at risk of MetS (central obesity plus 1 additional MetS risk factor, n = 61). Participants were randomly assigned to either the peanut arm (56 g/d as snacks, n = 113) or the control arm (isocaloric white rice bars, n = 111) for 12 wk. Results: A total of 209 participants (93.3%) completed the 12-wk intervention with a compliance rate > 85% among all participants. No between-group differences were found for improvements in fasting glucose, HDL cholesterol, waist circumference, and body weight. Participants in the peanut group had a significantly higher MetS reversion rate (no longer meeting MetS criteria after the 12-wk trial) than those in the control group (RR: 2.33; 95% CI: 1.10, 4.89; P = 0.026). Conclusions: Including peanuts as a snack in the habitual diet in place of a refined-grain snack did not significantly change glycemic or lipid parameters, but improved overall MetS risk without promoting weight gain among Chinese adults at high risk of cardiometabolic diseases. Further larger-scale trials are needed to confirm these findings and elucidate underlying biological mechanisms. This trial was registered at clinicaltrials.gov as NCT03194152.