The use and implementation of omalizumab as food allergy treatment: Consensus-based guidance and Work Group Report of the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology.

Omalizumab was recently approved by the US Food and Drug Administration for treatment of any single food allergy or multiple food allergies in children aged 1 year and older and adults. There is currently no formal guidance regarding recommended best practices for omalizumab use in food allergy, including patient selection, anticipated goals and outcomes of therapy, procedure for monitoring patients who elect to start omalizumab therapy, and ways in which omalizumab can be incorporated into the landscape of food allergy management and daily clinical practice. This work group report was developed by the food allergy therapies subcommittee of the Adverse Reactions to Foods Committee within the American Academy of Allergy, Asthma & Immunology.

The use of adjunctive therapies during oral immunotherapy: A focus on biologics.

Oral immunotherapy (OIT), thus far, is the most evaluated therapeutic approach for food allergy. However, OIT is not known to lead to a cure, and it carries a risk for allergic reactions. Adjunct therapies to OIT are currently being investigated to evaluate their effect on safety and outcome.

High-resolution epitope mapping by AllerScan reveals relationships between IgE and IgG repertoires during peanut oral immunotherapy.

Peanut allergy can result in life-threatening reactions and is a major public health concern. Oral immunotherapy (OIT) induces desensitization to food allergens through administration of increasing amounts of allergen. To dissect peanut-specific immunoglobulin E (IgE) and IgG responses in subjects undergoing OIT, we have developed AllerScan, a method that leverages phage-display and next-generation sequencing to identify the epitope targets of peanut-specific antibodies.

Biologics and Novel Therapies for Food Allergy.

Food allergy is a significant public health burden affecting around 10% of adults and 8% of children. Although the first peanut oral immunotherapy product received Food and Drug Administration approval in 2020, there is still an unmet need for more effective therapeutic options that minimize the risk of anaphylaxis, nutritional deficiencies, and patient's quality of life. Biologics are promising modalities, as they may improve compliance, target multiple food allergies, and treat other concomitant atopic diseases.

The microbial origins of food allergy.

Food allergy (FA) is a significant public health issue, propelled by its rapidly increasing prevalence. Its sharp rise into prominence has focused attention on causative environmental factors and their interplay with the immune system in disease pathogenesis. In that regard, there is now substantial evidence that alterations in the gut microbiome early in life imprint the host gut mucosal immunity and may play a critical role in precipitating FA.

Regulatory T Cell-Derived TGF-β1 Controls Multiple Checkpoints Governing Allergy and Autoimmunity.

The mechanisms by which regulatory T (Treg) cells differentially control allergic and autoimmune responses remain unclear. We show that Treg cells in food allergy (FA) had decreased expression of transforming growth factor beta 1 (TGF-β1) because of interleukin-4 (IL-4)- and signal transducer and activator of transciription-6 (STAT6)-dependent inhibition of Tgfb1 transcription. These changes were modeled by Treg cell-specific Tgfb1 monoallelic inactivation, which induced allergic dysregulation by impairing microbiota-dependent retinoic acid receptor-related orphan receptor gamma t (ROR-γt) Treg cell differentiation.

Novel Therapies for Treatment of Food Allergy.

Food allergy prevalence has increased over the past 2 decades and is estimated to affect 8% of children and 4% to 10% of adults. There is an unmet need to evaluate new therapeutic modalities that may decrease the risk of food-induced anaphylaxis and improve patients' quality of life. Oral, epicutaneous, and sublingual food immunotherapies have different safety and efficacy profiles, and their long-term outcome and applicability are unclear.

Untargeted metabolomic profiling identifies disease-specific signatures in food allergy and asthma.

Background: Food allergy (FA) affects an increasing proportion of children for reasons that remain obscure. Novel disease biomarkers and curative treatment options are strongly needed.

Objective: We sought to apply untargeted metabolomic profiling to identify pathogenic mechanisms and candidate disease biomarkers in patients with FA.

Author Correction: Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Microbiota therapy acts via a regulatory T cell MyD88/RORγt pathway to suppress food allergy.

The role of dysbiosis in food allergy (FA) remains unclear. We found that dysbiotic fecal microbiota in FA infants evolved compositionally over time and failed to protect against FA in mice. Infants and mice with FA had decreased IgA and increased IgE binding to fecal bacteria, indicative of a broader breakdown of oral tolerance than hitherto appreciated.

AR101 Oral Immunotherapy for Peanut Allergy.

Background: Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions.

Methods: In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program.

Acquired Cold-Induced Urticaria in Pediatric Patients: A 22-Year Experience in a Tertiary Care Center (1996-2017).

Background: Acquired cold-induced urticaria (ACU) has not been well evaluated in pediatrics.

Objective: To further evaluate the presentation of ACU in children and associated risk of anaphylaxis.

Methods: A retrospective chart review was performed in children 18 years or younger diagnosed with ACU at Boston Children's Hospital (US, Northeast) from 1996 to 2017.

Long-Term Outcome of Peanut Oral Immunotherapy Facilitated Initially by Omalizumab.

Background: We successfully used omalizumab to facilitate peanut oral immunotherapy (OIT) in children with reactivity to ≤50mg peanut protein and with high peanut IgE (median, 229 kU/L).

Objective: We report on long-term OIT outcomes in these patients, including dosing changes, adverse events, peanut immunoglobulin changes, and quality of life (QoL).

Methods: Patients were followed for up to 72 months (67 months of maintenance).

Defective TLR9-driven STAT3 activation in B cells of patients with CVID.

B cell activation by Toll-like receptor 9 (TLR9) ligands is dependent on STAT3 and is important for optimal antibody responses to microbial antigens. B cells from patients with common variable immune deficiency (CVID) have impaired proliferation and differentiation in response to the TLR9 ligand CpG, despite normal levels of TLR9 expression. We demonstrate that CpG-driven STAT3 phosphorylation, but not activation of NFκB and p38, is selectively impaired in B cells from CVID patients.

A twenty-two-year experience with Hymenoptera venom immunotherapy in a US pediatric tertiary care center 1996-2018.

Background: The rate of systemic reactions (SRs) to venom immunotherapy (VIT) in children has not been well evaluated.

Objective: To evaluate the rate of SRs to VIT in pediatric patients age 5 to 18 years who were treated with a standard protocol.

Methods: A retrospective chart review was conducted to identify patients who received VIT at Boston Children's Hospital from 1996 through 2018.

Systemic Reactions in Pediatric Patients Receiving Standardized Allergen Subcutaneous Immunotherapy with and without Seasonal Dose Adjustment.

Background: The 2003 Joint Task Force on Practice Parameters recommended standardizing allergen subcutaneous immunotherapy (SCIT). Data from longitudinal surveillance survey in North America reported a systemic reaction (SR) rate of 0.1% to 0.