Management of Food Allergies and Food-Related Anaphylaxis.

Importance: An estimated 7.6% of children and 10.8% of adults have IgE-mediated food-protein allergies in the US.

Intestinal Helminth Infection Impairs Oral and Parenteral Vaccine Efficacy.

The impact of endemic parasitic infection on vaccine efficacy is an important consideration for vaccine development and deployment. We have examined whether intestinal infection with the natural murine helminth Heligmosomoides polygyrus bakeri alters Ag-specific Ab and cellular immune responses to oral and parenteral vaccination in mice. Oral vaccination of mice with a clinically relevant, live, attenuated, recombinant Salmonella vaccine expressing chicken egg OVA (Salmonella-OVA) induced the accumulation of activated, OVA-specific T effector cells rather than OVA-specific regulatory T cells in the GALT.

Novel peanut-specific human IgE monoclonal antibodies enable screens for inhibitors of the effector phase in food allergy.

Background: 10% of US residents have food allergies, including 2% with peanut allergy. Mast cell mediators released during the allergy effector phase drive allergic reactions. Therefore, targeting sensitized mast cells may prevent food allergy symptoms.

The Meat of the Matter: Understanding and Managing Alpha-Gal Syndrome.

Alpha-gal syndrome is an unconventional food allergy, characterized by IgE-mediated hypersensitivity responses to the glycan galactose-alpha-1,3-galactose (alpha-gal) and not to a food-protein. In this review, we discuss how alpha-gal syndrome reframes our current conception of the mechanisms of pathogenesis of food allergy. The development of alpha-gal IgE is associated with tick bites though the possibility of other parasites promoting sensitization to alpha-gal remains.

Treatment for food allergy: Current status and unmet needs.

The treatment of food allergy has traditionally relied on avoidance of the offending food(s) and use of emergency medications in the event of accidental exposures. However, this long-standing paradigm is beginning to shift, as a variety of treatment approaches have been and are being developed. This report provides an overview of the past, present, and future landscape of interventional clinical trials for the treatment of food allergy.

Targeting CD22 on memory B cells to induce tolerance to peanut allergens.

Background: Circulating IgE and subsequent severe allergic reactions to peanut are sustained and propagated by recall of peanut allergen-specific memory B cells.

Objectives: This study aimed to determine whether targeting mouse and human CD22 on peanut-specific memory B cells induces tolerance to peanut allergens.

Methods: Siglec-engaging tolerance-inducing antigenic liposomes (STALs) codisplaying peanut allergens (Ara h 1, Ara h 2, or Ara h 3) and high-affinity CD22 ligand (CD22L-STALs) were employed in various mouse models (BALB/cJ, C57BL/6, human CD22 transgenic, and NSG) of peanut allergy.

Mouse Models of Food Allergy in the Pursuit of Novel Treatment Modalities.

The prevalence of IgE-mediated food allergies has increased dramatically in the past three decades, now affecting up to 10% of the US population. IgE-mediated food allergy is an immunologic disease, involving a variety of cells, including B and T cells, mast cells, basophils, ILC2s, and epithelial cells. Mouse models of food allergy mimic the overall immunologic processes known to exist in humans.

Where's the Beef? Understanding Allergic Responses to Red Meat in Alpha-Gal Syndrome.

Alpha-gal syndrome (AGS) describes a collection of symptoms associated with IgE-mediated hypersensitivity responses to the glycan galactose-alpha-1,3-galactose (alpha-gal). Individuals with AGS develop delayed hypersensitivity reactions, with symptoms occurring >2 h after consuming mammalian ("red") meat and other mammal-derived food products. The mechanisms of pathogenesis driving this paradigm-breaking food allergy are not fully understood.

Safety of peanut (Arachis hypogaea) allergen powder-dnfp in children and teenagers with peanut allergy: Pooled summary of phase 3 and extension trials.

Background: Peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; previously known as AR101) is a daily oral immunotherapy approved to mitigate allergic reactions after accidental peanut exposure in peanut-allergic individuals aged 4-17 years.

Objective: We sought to comprehensively summarize the PTAH safety profile for up to ∼2 years of treatment.

Methods: Safety and adverse event (AE) data from participants aged 4-17 years from 3 controlled, phase 3 and 2 open-label extension trials were pooled and assessed.

The airway as a route of sensitization to peanut: An update to the dual allergen exposure hypothesis.

Food allergies have increased at an alarming rate over the past 2 decades, indicating that environmental factors are driving disease progression. It has been postulated that sensitization to foods, in particular, peanut, occurs through impaired skin. Peanut allergens have been quantified in household dust and may be the culprit source.

T and B Lymphocyte Transcriptional States Differentiate between Sensitized and Unsensitized Individuals in Alpha-Gal Syndrome.

The mechanisms of pathogenesis driving alpha-gal syndrome (AGS) are not fully understood. Differences in immune gene expression between AGS individuals and non-allergic controls may illuminate molecular pathways and targets critical for AGS development. We performed immune expression profiling with RNA from the peripheral blood mononuclear cells (PBMCs) of seven controls, 15 AGS participants, and two participants sensitized but not allergic to alpha-gal using the NanoString nCounter PanCancer immune profiling panel, which includes 770 genes from 14 different cell types.

Strategies for Mast Cell Inhibition in Food Allergy.

Mast cells are tissue resident allergic effector cells that drive IgE-mediated food allergies. There are several steps leading to mast cell activation in the context of allergic disease that can be targeted to prevent mast cell activation and degranulation. These include blocking IgE-FcεRI crosslinking and type 2 cytokine receptor activation; modulating cell-surface neural chemical receptors; stabilizing mast cell membranes to prevent co-localization of activating receptors; impeding intracellular signaling; and engaging cell surface inhibitory receptors.

'Doc, will I ever eat steak again?': diagnosis and management of alpha-gal syndrome.

Purpose Of Review: Alpha-gal syndrome encompasses a constellation of symptoms associated with immune-mediated hypersensitivity responses to galactose-alpha-1,3-galactose (alpha-gal). The purpose of this review is to discuss our current understanding of the etiology, clinical symptoms, natural history, epidemiology, and management of alpha-gal syndrome.

Recent Findings: Sensitization to alpha-gal is associated with bites from ectoparasites like the lone star tick Amblyomma americanum.

Timing of exposure to environmental adjuvants is critical to mitigate peanut allergy.

Toll-like receptor ligands in indoor dust act as environmental adjuvants to promote sensitization to inhaled peanut in mice. The timing of exposure to environmental adjuvants relative to peanut is a determinant of peanut allergy development.

IgE producers in the gut expand the gut's role in food allergy.

Details about IgE-producing B cells in the gut in the context of food allergy are scarce, despite the frequent exposure of the gut and its associated lymphoid tissues to dietary antigens. A new study finds that IgE-producing B cells are enriched in gut tissues and are probably generated from local antibody isotype switching.

Peanut applied to the skin of nonhuman primates induces antigen-specific IgG but not IgE.

Introduction: Previous studies in humans support the dual-allergen exposure hypothesis, and several studies in mouse models have demonstrated that cutaneous exposure to disrupted or intact skin can lead to sensitization to peanut. However, the field lacks definitive evidence that cutaneous exposure leads to peanut allergy in humans or other primates.

Methods: Peanut extract was applied to the shaved back of the neck of four male and four female African green monkeys three times per week for 4 weeks.

Glycolipid-mediated basophil activation in alpha-gal allergy.

Alpha-gal-containing glycolipids activate basophils sensitized with plasma from alpha-gal allergic subjects in an IgE-dependent manner suggesting a role for glycolipid in the effector phase of IgE-mediated food allergy.

Genetic diversity between mouse strains allows identification of the CC027/GeniUnc strain as an orally reactive model of peanut allergy.

Background: Improved animal models are needed to understand the genetic and environmental factors that contribute to food allergy.

Objective: We sought to assess food allergy phenotypes in a genetically diverse collection of mice.

Methods: We selected 16 Collaborative Cross (CC) mouse strains, as well as the classic inbred C57BL/6J, C3H/HeJ, and BALB/cJ strains, for screening.

Adjuvanted Immunotherapy Approaches for Peanut Allergy.

Food allergies are a growing public health concern with an estimated 8% of US children affected. Peanut allergies are also on the rise and often do not spontaneously resolve, leaving individuals at-risk for potentially life-threatening anaphylaxis throughout their lifetime. Currently, two forms of peanut immunotherapy, oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT), are in Phase III clinical trials and have shown promise to induce desensitization in many subjects.

High- and low-dose oral immunotherapy similarly suppress pro-allergic cytokines and basophil activation in young children.

Background: Mechanisms underlying oral immunotherapy (OIT) are unclear and the effects on immune cells at varying maintenance doses are unknown.

Objective: We aimed to determine the immunologic changes caused by peanut OIT in preschool aged children and determine the effect on these immune responses in groups ingesting low or high-dose peanut OIT (300 mg or 3000 mg, respectively) as maintenance therapy.

Methods: Blood was drawn at several time-points throughout the OIT protocol and PBMCs isolated and cultured with peanut antigens.