IgE binding epitope mapping with TL1A tagged peptides.

Linear IgE epitopes play essential roles in persistent allergies, including peanut and tree nut allergies. Using chemically synthesized peptides attached to membranes and microarray experiments is one approach for determining predominant epitopes that has seen success. However, the overall expense of this approach and the inherent challenges in scaling up the production and purification of synthetic peptides precludes the general application of this approach.

Expression, purification, characterization, and patient IgE reactivity of new macadamia nut iso-allergen.

Structural and functional information about food allergens is essential for understanding the allergenicity of food proteins. All allergens belong to a small number of protein families. Various allergens from different families have been successfully produced recombinantly in E.

STAT5B restrains human B-cell differentiation to maintain humoral immune homeostasis.

Background: Lymphocyte differentiation is regulated by coordinated actions of cytokines and signaling pathways. IL-21 activates STAT1, STAT3, and STAT5 and is fundamental for the differentiation of human B cells into memory cells and antibody-secreting cells. While STAT1 is largely nonessential and STAT3 is critical for this process, the role of STAT5 is unknown.

A positive feedback loop reinforces the allergic immune response in human peanut allergy.

Food allergies are a leading cause of anaphylaxis, and cellular mechanisms involving antigen presentation likely play key roles in their pathogenesis. However, little is known about the response of specific antigen-presenting cell (APC) subsets to food allergens in the setting of food allergies. Here, we show that in peanut-allergic humans, peanut allergen drives the differentiation of CD209+ monocyte-derived dendritic cells (DCs) and CD23+ (FcєRII) myeloid dendritic cells through the action of allergen-specific CD4+ T cells.

Can the biomolecular corona induce an allergic reaction?-A proof-of-concept study.

Ferumoxytol nanoparticles are being used clinically for the treatment of anemia and molecular imaging in patients. It is well documented that while most patients tolerate ferumoxytol well, a small percentage of patients (i.e.

Targeted DNA methylation profiling reveals epigenetic signatures in peanut allergy.

DNA methylation (DNAm) has been shown to play a role in mediating food allergy; however, the mechanism by which it does so is poorly understood. In this study, we used targeted next-generation bisulfite sequencing to evaluate DNAm levels in 125 targeted highly informative genomic regions containing 602 CpG sites on 70 immune-related genes to understand whether DNAm can differentiate peanut allergy (PA) versus nonallergy (NA). We found PA-associated DNAm signatures associated with 12 genes (7 potentially novel to food allergy, 3 associated with Th1/Th2, and 2 associated with innate immunity), as well as DNAm signature combinations with superior diagnostic potential compared with serum peanut-specific IgE for PA versus NA.

Aging and CMV discordance are associated with increased immune diversity between monozygotic twins.

Background: Broadly, much of variance in immune system phenotype has been linked to the influence of non-heritable factors rather than genetics. In particular, two non-heritable factors: aging and human cytolomegavirus (CMV) infection, have been known to account for significant inter-individual immune variance. However, many specific relationships between them and immune composition remain unclear, especially between individuals over narrower age ranges.

Regulation of peanut-specific CD8 T cells from nonallergic individuals.

Peanut-specific CD8 T cells in nonallergic individuals are not deleted, but have an expansion block that can be released by impairing regulatory T cell associated signaling pathways.

Transcriptional changes in peanut-specific CD4+ T cells over the course of oral immunotherapy.

Oral immunotherapy (OIT) can successfully desensitize allergic individuals to offending foods such as peanut. Our recent clinical trial (NCT02103270) of peanut OIT allowed us to monitor peanut-specific CD4+ T cells, using MHC-peptide Dextramers, over the course of OIT. We used a single-cell targeted RNAseq assay to analyze these cells at 0, 12, 24, 52, and 104 weeks of OIT.

Mass cytometry reveals cellular fingerprint associated with IgE+ peanut tolerance and allergy in early life.

IgE-mediated peanut allergic is common, often serious, and usually lifelong. Not all individuals who produce peanut-specific IgE will react upon consumption of peanut and can eat the food without adverse reactions, known as sensitized tolerance. Here, we employ high-dimensional mass cytometry to define the circulating immune cell signatures associated with sensitized tolerance and clinical allergy to peanut in the first year of life.

Phase 2a randomized, placebo-controlled study of anti-IL-33 in peanut allergy.

BACKGROUNDIL-33, found in high levels in participants with allergic disorders, is thought to mediate allergic reactions. Etokimab, an anti-IL-33 biologic, has previously demonstrated a good safety profile and favorable pharmacodynamic properties in many clinical studies.METHODSIn this 6-week placebo-controlled phase 2a study, we evaluated the safety and the ability of a single dose of etokimab to desensitize peanut-allergic adults.

Sustained outcomes in oral immunotherapy for peanut allergy (POISED study): a large, randomised, double-blind, placebo-controlled, phase 2 study.

Background: Dietary avoidance is recommended for peanut allergies. We evaluated the sustained effects of peanut allergy oral immunotherapy (OIT) in a randomised long-term study in adults and children.

Methods: In this randomised, double-blind, placebo-controlled, phase 2 study, we enrolled participants at the Sean N Parker Center for Allergy and Asthma Research at Stanford University (Stanford, CA, USA) with peanut allergy aged 7-55 years with a positive result from a double-blind, placebo-controlled, food challenge (DBPCFC; ≤500 mg of peanut protein), a positive skin-prick test (SPT) result (≥5 mm wheal diameter above the negative control), and peanut-specific immunoglobulin (Ig)E concentration of more than 4 kU/L.

Almond () Allergen Pru du 8, the First Member of a New Family of Food Allergens.

An almond allergen with two known short peptide sequences was reported as the almond 2S albumin but was later suspected to be almond vicilin. However, this allergen was not designated by the World Health Organization/International Union of Immunological Societies. This study aimed to determine the true identity of this elusive almond allergen.

Allergen-specific CD8 T cells in peanut-allergic individuals.

CD8 T cells are seldom considered in IgE mediated food allergy; we show that peanut specific CD8 T cells are increased in peanut allergic human subjects.

Identification of Almond ( Prunus dulcis) Vicilin As a Food Allergen.

Almond is one of the tree nuts listed by U.S. FDA as a food allergen source.

Identification, characterization, and initial epitope mapping of pine nut allergen Pin k 2.

The aims of this study were to predict, identify and characterize pine nut allergens. Korean pine (Pinus koraiensis) vicilin was predicted to be a pine nut allergen. Recombinant Korean pine vicilin was expressed in E.

Purification and Characterization of a Black Walnut (Juglans nigra) Allergen, Jug n 4.

Tree nuts as a group cause a significant number of fatal anaphylactic reactions to foods. Walnuts (Juglans spp.) are one of the leading causes of allergic reactions to tree nuts in the U.

Identification and Characterization of a New Pecan [Carya illinoinensis (Wangenh.) K. Koch] Allergen, Car i 2.

The 7S vicilin and 11S legumin seed storage globulins belong to the cupin protein superfamily and are major food allergens in many foods from the "big eight" food allergen groups. Here, for the first time, pecan vicilin was found to be a food allergen. Western blot experiments revealed that 30% of 27 sera used in this study and 24% of the sera from 25 patients with double-blind, placebo controlled clinical pecan allergy contained IgE antibodies specific to pecan vicilin.

Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets.

Allergen immunotherapy can desensitize even subjects with potentially lethal allergies, but the changes induced in T cells that underpin successful immunotherapy remain poorly understood. In a cohort of peanut-allergic participants, we used allergen-specific T-cell sorting and single-cell gene expression to trace the transcriptional "roadmap" of individual CD4+ T cells throughout immunotherapy. We found that successful immunotherapy induces allergen-specific CD4+ T cells to expand and shift toward an "anergic" Th2 T-cell phenotype largely absent in both pretreatment participants and healthy controls.

Single B-cell deconvolution of peanut-specific antibody responses in allergic patients.

Background: The frequencies, cellular phenotypes, epitope specificity, and clonal diversity of allergen-specific B cells in patients with food allergy are not fully understood but are of major pathogenic and therapeutic significance.

Objective: We sought to characterize peanut allergen-specific B-cell populations and the sequences and binding activities of their antibodies before and during immunotherapy.

Methods: B cells binding fluorescently labeled Ara h 1 or Ara h 2 were phenotyped and isolated by means of flow cytometric sorting from 18 patients at baseline and 13 patients during therapy.

Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3).

Background: The mechanisms contributing to clinical immune tolerance remain incompletely understood. This study provides evidence for specific immune mechanisms that are associated with a model of operationally defined clinical tolerance.

Objective: Our overall objective was to study laboratory changes associated with clinical immune tolerance in antigen-induced T cells, basophils, and antibodies in subjects undergoing oral immunotherapy (OIT) for peanut allergy.