Peanuts are Leguminosae, commonly known as the legume or pea family, and peanut allergy is among the most common food allergies and the most common cause of fatal food reactions and anaphylaxis.
The prevalence of peanut allergy increased 3.5-fold over the past two decades reaching 1.4–2% in Europe and the United States. The reasons for this increase in prevalence are likely multifaceted. Sensitization via the skin appears to be associated with the development of peanut allergy and atopic eczema in infancy is associated with a high risk of developing peanut allergy.
The prevalence of peanut allergy in the United States has been reported to have increased 3.5-fold over the past two decades, from 0.4% in 1997 to 0.8% in 2002 and 1.4% in 2008 [8,9,10]. Currently, 1–2% of children are affected in the Western world [11,12,13]. Although the trend in increased prevalence of peanut allergy is seen in most regions, it is also important to note that the variability of estimates is in part due to the different diagnostic methods, the age of the cohorts, and the populations studied [11,12,13].
The reasons for the increase in prevalence of peanut allergy are not known and are likely multifaceted; however, sensitization via the skin appears to be associated with the later development of peanut allergy  and atopic eczema in infancy is associated with a high risk of developing peanut allergy .
Several studies have shown that disturbances in cutaneous barrier function—e.g., with lower formation of filaggrin—may promote peanut sensitization [16, 17]. By contrast, early and regular consumption of peanut protein from infancy onward in relevant amounts promotes tolerance development, especially in at-risk children with atopic eczema or other food allergies [18,19,20].
Peanut and hazelnut allergies frequently occur at preschool age, in 55% of children by 2 years of age and in 92% by 7 years of age . The later onset of clinical symptoms is usually explained by later first consumption. The development of primary allergy to peanut after previous problem-free consumption is a rarity.
Approximately one third of patients are clinically allergic both to peanuts and to tree nuts . In a recent prospective study of cross-allergy in peanut and nut allergic patients by Brough et al., approximately 30% of patients also reacted to cashew, 28% to walnut and pistachio, 22% to hazelnut, and 20% to pecan .
Clinical symptoms and diagnostics
Allergies to peanut have a range of clinical presentations from cutaneous manifestations to life-threatening systemic reactions. Peanut allergy mostly manifests as isolated cutaneous symptoms (94%), or as respiratory tract (42%) and/or gastrointestinal system (33%) symptoms. An allergic response to peanuts usually occurs within minutes of exposure.
In one study, 95% of patients reacted within 20 min ; in another study, the median onset of a reaction after oral challenge was as late as 55 min . In large cohort studies, approximately one third of patients reacted with the clinical symptoms of anaphylaxis to accidental consumption [25, 26].
Some allergic patients react to very small (milligrams) amounts of peanut protein, but many react only to larger amounts equivalent to more than one peanut kernel [25,26,27,28,29,30]. In a survey of 669 peanut-allergic participants, the amount of food allergen triggering the accidental reaction was able to be estimated in 238 participants (35.5%). Median estimated eliciting dose in real life was 125 mg (interquartile range: 34–177 mg) of peanut protein .
To better assess the different risk profiles, a whole series of peanut molecular antigens (allergen components) have been identified so far (Ara h 1–11; [31,32,33]). Of these, Ara h 1, 2, 3, and 6 are associated with higher-grade allergic/anaphylactic reactions after peanut protein exposure, and the majority of clinically relevant peanut-allergic patients produce antigen-specific IgE antibodies to these allergens [34,35,36,37].
Elevated serum IgE levels for the Ara h 2 component have been shown to be particularly relevant for diagnostics [38, 39]. Specific IgE against Ara h 8, a PR10 protein and Bev 1-homologous allergen, on the other hand, indicates a cross-allergy in the context of an existing birch pollen sensitization, with absent or only mild symptoms on peanut consumption, most likely in the context of an oral allergy syndrome.
Double-blind placebo-controlled oral allergen challenge (DBPCFC) is considered the gold standard for the diagnosis of food allergy, including peanut allergy . However, in daily practice, a combination of a typical history of an allergic reaction and a positive skin prick test or the detection of serum-specific IgE antibodies against peanut, and especially against the peanut Ara h 2 storage protein, often confirms the diagnosis of a clinically relevant peanut allergy.
An allergen-specific inhibitor devised by researchers at the University of Notre Dame and the Indiana University School of Medicine has successfully prevented potentially life-threatening allergic responses to peanuts.
The results of the new study were just published in Science Translational Medicine.
Peanut-induced allergy is an immunoglobulin E (IgE)–mediated type I hypersensitivity reaction that manifests symptoms ranging from local edema to life-threatening anaphylaxis. Although there are treatments for symptoms in patients with allergies resulting from allergen exposure, there are few preventive therapies other than strict dietary avoidance or oral immunotherapy, neither of which are successful in all patients.
We have previously designed a covalent heterobivalent inhibitor (cHBI) that binds in an allergen-specific manner as a preventive for allergic reactions. Building on previous in vitro testing, here, we developed a humanized mouse model to test cHBI efficacy in vivo.
Nonobese diabetic–severe combined immunodeficient γc-deficient mice expressing transgenes for human stem cell factor, granulocyte-macrophage colony-stimulating factor, and interleukin-3 developed mature functional human mast cells in multiple tissues and displayed robust anaphylactic reactions when passively sensitized with patient-derived IgE monoclonal antibodies specific for peanut Arachis hypogaea 2 (Ara h 2).
The allergic response in humanized mice was IgE dose dependent and was mediated by human mast cells. Using this humanized mouse model, we showed that cHBI prevented allergic reactions for more than 2 weeks when administered before allergen exposure. cHBI also prevented fatal anaphylaxis and attenuated allergic reactions when administered shortly after the onset of symptoms. cHBI impaired mast cell degranulation in vivo in an allergen-specific manner. cHBI rescued the mice from lethal anaphylactic responses during oral Ara h 2 allergen–induced anaphylaxis. Together, these findings suggest that cHBI has the potential to be an effective preventative for peanut-specific allergic responses in patients.
Specific strategies to prevent anaphylaxis in individuals with food allergy are urgently needed. Here, Alakhras et al. tested a covalent heterobivalent inhibitor (cHBI) specific to peanut Ara h 2 allergen as a treatment for peanut allergy.
The cHBI used in this study binds to Ara h 2-specific IgE; this prevents binding of Ara h 2 allergens to IgE and, as a consequence, prevents activation of mast cells.
The authors found that treatment of peanut-reactive humanized mice with Ara h 2-specific cHBI protected mice against peanut-induced allergic reactions for more than two weeks. cHBI treatment also conferred protection when given shortly after onset of anaphylactic symptoms, highlighting potential clinical use of cHBI as both a preventative and treatment for food allergy.—CM
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- More information: Nada S. Alakhras et al, Peanut allergen inhibition prevents anaphylaxis in a humanized mouse model, Science Translational Medicine (2023). DOI: 10.1126/scitranslmed.add6373