Differential T follicular helper cell phenotypes distinguish IgE-mediated milk allergy from eosinophilic esophagitis in children.

Background: IgE-mediated food allergy and eosinophilic esophagitis (EoE) are diseases commonly triggered by milk. Milk-responsive CD4 T cells producing type 2 cytokines are present in both diseases, yet the clinical manifestation of disease in milk allergy (MA) and EoE are distinct.

Objective: We sought to identify differences in CD4 T cells between EoE and MA that may be responsible for distinct disease manifestations.

Contribution of T cell subsets to different food allergic diseases.

Food allergies occur due to a lack of tolerance to the proteins found in foods. While IgE- and non-IgE-mediated food allergies have different clinical manifestations, epidemiology, pathophysiology, and management, they share dysregulated T cell responses. Recent studies have shed light on the contributions of different T cell subsets to the development and persistence of different food allergic diseases.

Joint transcriptomic and cytometric study of children with peanut allergy reveals molecular and cellular cross talk in reaction thresholds.

Background: Reaction thresholds in peanut allergy are highly variable. Elucidating causal relationships between molecular and cellular processes associated with variable thresholds could point to therapeutic pathways for raising thresholds.

Objective: The aim of this study was to characterize molecular and cellular systemic processes associated with reaction threshold in peanut allergy and causal relationships between them.

Evaluation of the Suppressive Capacity of Regulatory T Cells in Food Allergy Research.

Regulatory T cells (Treg) exert a crucial role in the suppression of exacerbated T helper (Th) cell responses, including those of type 2 Th (Th2) cells, and in the maintenance of tolerance to environmental antigens and food allergens. The functional capacity of Tregs to suppress Th2 responses has been studied through activation and immunosuppression assays using cells from mice and humans. The immunosuppression assay is an essential in vitro tool that allows the evaluation of the Treg capacity to limit the proliferation and expansion of conventional T cells.

Coculture of Human Dendritic and T Cells for the Study of Specific T Cell-Mediated Responses Against Food Allergens.

Dendritic cells (DCs) connect innate and adaptive immunity by sampling, capturing, processing, and presenting the allergen to distinct subsets of CD4 T cells. In food allergy, this process leads to the generation of allergen-specific Th2 responses and the production of type 2 cytokines that ultimately induce the synthesis of IgE by allergen-specific B cells. In this chapter, we have described different protocols for the isolation of circulating DCs as well as the generation of DC-like cells derived from autologous peripheral monocytes and the human monocytic THP-1 cell line.

JAK1 inhibition with abrocitinib decreases allergen-specific basophil and T-cell activation in pediatric peanut allergy.

Background: JAK1 is a signaling molecule downstream of cytokine receptors, including IL-4 receptor α. Abrocitinib is an oral JAK1 inhibitor; it is a safe and effective US Food and Drug Administration-approved treatment for adults with moderate-to-severe atopic dermatitis.

Objective: Our objective was to investigate the effect of abrocitinib on basophil activation and T-cell activation in patients with peanut allergy to determine the potential for use of JAK1 inhibitors as a monotherapy or an adjuvant to peanut oral immunotherapy.

Reservoirs of allergic memory.

Two preprints by Koenig et al. and Ota et al. characterize a subset of memory B cells that can retain allergen-specific IgE memory.

Targeting type 2 immunity and the future of food allergy treatment.

IgE-mediated food allergy affects 6-8% of the population in the United States. Type 2 immune responses are central to the pathogenesis of food allergy, but type 2 CD4+ T cell responses have been found to be heterogeneous in food allergy suggesting a division of labor between Tfh13 and peTH2 cells in promotion of IgE class switching, modulation of intestinal barrier function, and regulation of mast cell expansion. Oral immunotherapy for the treatment of food allergy incompletely targets subsets of type 2 immunity in a transient manner, but new therapeutics targeting different levels of type 2 immunity are in current or planned trials for food allergy.

Jak out of the box: Targeting Bruton's tyrosine kinase, sialic acid-binding immunoglobulin-like lectin-8, and Janus kinase 1 in food allergy.

There has been rapid growth in the field of immunoglobulin E-mediated food allergy therapeutics, with 1 US Food and Drug Administration-approved therapy in 2020 and several others in various stages of investigation. Oral immunotherapy is the approach with the longest track record of study and provides desensitization for most individuals undertaking the therapy. However, the therapy must be maintained for continued clinical protection, and adverse effects of the therapy are frequent.

Oral tolerance and oral immunotherapy for food allergy: Evidence for common mechanisms?

Food allergies affect up to 10% of the US population, can be life-threatening, and have a significant negative impact on quality of life. Delayed dietary introduction of foods in childhood can hinder the induction of oral tolerance, an active regulatory response to foods that prevents the development of food allergy. Some children outgrow their food allergies naturally, while many others have persistent, lifelong food allergy for which there are few therapeutic options.

Untargeted serum metabolomic analysis reveals a role for purinergic signaling in FPIES.

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy with a typical onset in infancy. Its symptoms are distinct from those of IgE-mediated food allergies and include severe repetitive vomiting, lethargy, and pallor. FPIES reactions are associated with T17 cytokines and a systemic innate immune activation; however, the link between immune activation and symptoms is poorly understood.

Allergen recognition by specific effector Th2 cells enables IL-2-dependent activation of regulatory T-cell responses in humans.

Type 2 allergen-specific T cells are essential for the induction and maintenance of allergies to foods, and Tregs specific for these allergens are assumed to be involved in their resolution. However, it has not been convincingly demonstrated whether allergen-specific Treg responses are responsible for the generation of oral tolerance in humans. We observed that sustained food allergen exposure in the form of oral immunotherapy resulted in increased frequency of Tregs only in individuals with lasting clinical tolerance.

Mass Cytometry Analysis of Whole Blood Response to an Allergen.

Mass cytometry allows for the use of highly multiplexed antibody panels due to the lack of spill-over between channels detected by mass spectrometry. An advantage over fluorescence cytometry is the relative lack of background, which provides excellent resolution for detection of phosphoproteins and quantification of cell signaling. We have applied mass cytometry to the analysis of whole blood staining after ex vivo stimulation with peanut allergen (Tordesillas et al.

Rapid, scalable assessment of SARS-CoV-2 cellular immunity by whole-blood PCR.

Fast, high-throughput methods for measuring the level and duration of protective immune responses to SARS-CoV-2 are needed to anticipate the risk of breakthrough infections. Here we report the development of two quantitative PCR assays for SARS-CoV-2-specific T cell activation. The assays are rapid, internally normalized and probe-based: qTACT requires RNA extraction and dqTACT avoids sample preparation steps.

Update on Food Protein-Induced Enterocolitis Syndrome (FPIES).

Purpose Of Review: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by delayed, and potentially severe, gastrointestinal symptoms. Since the advent of a specific diagnostic code and establishment of diagnostic guidelines, our understanding of this condition has grown.

Recent Findings: FPIES affects patients from early infancy into adulthood.

The year in food allergy.

Research into food allergy continues to rapidly evolve, accompanying and driving real changes in the clinical approach to these diseases. The past year has seen the rollout of the first treatment approved for active management of food allergy, more data on alternative methods of treatment, the continued evolution of strategies for prevention of food allergy, a renewed interest in phenotyping food allergy subtypes, and, importantly, key new insights into the pathophysiology of food allergy. We expect that in the coming years, the therapies that are in preclinical or early clinical evaluation now will make their way to the clinic, finally allowing the possibility of safe and effective treatments for food allergy.

Pathophysiology of Non-IgE-Mediated Food Allergy.

Non-IgE-mediated food allergies are a group of disorders characterized by subacute or chronic inflammatory processes in the gut. Unlike IgE mediated food allergies that may result in multi-organ system anaphylaxis, the non-IgE mediated food allergies primarily affect the gastrointestinal tract. This review outlines the clinical manifestations, epidemiology, pathophysiology, and management of non-IgE-mediated food allergies.

Allergen-specific T cells and clinical features of food allergy: Lessons from CoFAR immunotherapy cohorts.

Background: Allergen-specific IL-4 and IL-13 CD4 cells (type 2 cells) are essential for helping B cells to class-switch to IgE and establishing an allergic milieu in the gastrointestinal tract. The role of T cells in established food allergy is less clear.

Objective: We examined the food allergen-specific T-cell response in participants of 2 food allergen immunotherapy trials to assess the relationship of the T-cell response to clinical phenotypes, including response to immunotherapy.

Differential effects of the second SARS-CoV-2 mRNA vaccine dose on T cell immunity in naive and COVID-19 recovered individuals.

The rapid development of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the design of accelerated vaccination schedules that have been extremely effective in naive individuals. While a two-dose immunization regimen with the BNT162b2 vaccine has been demonstrated to provide a 95% efficacy in naive individuals, the effects of the second vaccine dose in individuals who have previously recovered from natural SARS-CoV-2 infection has not been investigated in detail. In this study, we characterize SARS-CoV-2 spike-specific humoral and cellular immunity in naive and previously infected individuals during and after two doses of BNT162b2 vaccination.

Role of innate immunity and myeloid cells in susceptibility to allergic disease.

Allergic diseases, including asthma, food allergy, eczema, and allergic rhinitis, are common diseases increasing in prevalence. Allergy, a failure of immune tolerance to innocuous environmental allergens, is characterized by allergen-specific immune responses, including IgE antibodies and T helper and T follicular helper cells producing type 2 cytokines. Despite the central role of adaptive immunity in pathophysiology of allergy, there is a growing body of evidence indicating an important role for the innate immune system in allergic disease.

Acute FPIES reactions are associated with an IL-17 inflammatory signature.

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by profuse vomiting within hours of ingestion of the causative food. We have previously reported that FPIES is associated with systemic innate immune activation in the absence of a detectable antigen-specific antibody or T-cell response. The mechanism of specific food recognition by the immune system remains unclear.