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.

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.

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.

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.

Downregulation of exhausted cytotoxic T cells in gene expression networks of multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) presents with fever, inflammation and pathology of multiple organs in individuals under 21 years of age in the weeks following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although an autoimmune pathogenesis has been proposed, the genes, pathways and cell types causal to this new disease remain unknown. Here we perform RNA sequencing of blood from patients with MIS-C and controls to find disease-associated genes clustered in a co-expression module annotated to CD56CD57 natural killer (NK) cells and exhausted CD8 T cells.

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.

Immune Characterization of Bone Marrow-Derived Models of Mucosal and Connective Tissue Mast Cells.

Purpose: It is well appreciated that mast cells (MCs) demonstrate tissue-specific imprinting, with different biochemical and functional properties between connective tissue MCs (CTMCs) and mucosal MCs (MMCs). Although in vitro systems have been developed to model these different subsets, there has been limited investigation into the functional characteristics of the 2 major MC subsets. Here, we report the immunologic characterization of 2 MCs subsets developed in vitro from bone marrow progenitors modeling MMCs and CTMCs.

Egg-specific IgE and basophil activation but not egg-specific T-cell counts correlate with phenotypes of clinical egg allergy.

Background: Egg allergy is phenotypically heterogeneous. A subset of patients with egg allergy can tolerate egg in an extensively heated form. Inclusion of baked egg (BE) into the diet accelerates resolution of egg allergy.

Single-cell profiling of peanut-responsive T cells in patients with peanut allergy reveals heterogeneous effector T2 subsets.

Background: The contribution of phenotypic variation of peanut-specific T cells to clinical allergy or tolerance to peanut is not well understood.

Objectives: Our objective was to comprehensively phenotype peanut-specific T cells in the peripheral blood of subjects with and without peanut allergy (PA).

Methods: We obtained samples from patients with PA, including a cohort undergoing baseline peanut challenges for an immunotherapy trial (Consortium of Food Allergy Research [CoFAR] 6).

Impact of granulocyte contamination on PBMC integrity of shipped blood samples: Implications for multi-center studies monitoring regulatory T cells.

In centralized immune monitoring for a multi-center allergen immunotherapy trial, we observed frequent loss of CD4 T cell integrity following staining of cultured PBMCs with our regulatory T cell flow cytometry panel. Samples were marked by a loss of total cellular events, altered scatter properties, and reduced CD3CD4 events. This occurred only in samples that were stained with Foxp3 and were therefore treated with Foxp3 fixation-permeabilization buffer.

Transcriptional Profiling of Egg Allergy and Relationship to Disease Phenotype.

Background: Egg allergy is one of the most common food allergies of childhood. There is a lack of information on the immunologic basis of egg allergy beyond the role of IgE.

Objective: To use transcriptional profiling as a novel approach to uncover immunologic processes associated with different phenotypes of egg allergy.