Kinetics of epitope-specific IgE and IgG in early peanut allergy development and resolution.

Background: The development and resolution of peanut allergy (PA) was evaluated in children enrolled or screened for the Learning Early About Peanut (LEAP) intervention trial. The development of epitope-specific (es) IgE and es-IgG antibodies was evaluated in a subset of these children to determine whether their PA status could be predicted at 4-11 months of age.

Methods: Sera from 386 children enrolled or screened as part of the LEAP trial were assayed at 4-11 months (baseline) and 60 months of age, and final allergy status was established by oral food challenge at 60 months.

Factors associated with placebo response rate in randomized controlled trials of antiseizure medications for focal epilepsy.

Objective: Randomized controlled trials (RCTs) are necessary to evaluate the efficacy of novel treatments for epilepsy. However, there have been concerning increases in the placebo responder rate over time. To understand these trends, we evaluated features associated with increased placebo responder rate.

Baseline epitope-specific IgE profiles are predictive of sustained unresponsiveness or high threshold 1-year post oral immunotherapy in the POISED trial.

Background: Results from the POISED trial suggest that discontinuation of peanut oral immunotherapy can increase the risk of regaining clinical reactivity to peanut.

Objective: We sought to determine whether patients who achieved sustained unresponsiveness (SU) or sustained high threshold (SHT) have different baseline sequential epitope-specific IgE profiles than patients who achieved transient desensitization.

Methods: Subjects in the POISED trial (NCT02103270) were randomized to peanut (n = 95) or placebo (n = 25) for 24 months.

Utility of epitope-specific IgE, IgG4, and IgG1 antibodies for the diagnosis of wheat allergy.

Background: The bead-based epitope assay has been used to identify epitope-specific (es) antibodies and successfully used to diagnose clinical allergy to milk, egg, and peanut.

Objective: We sought to identify es-IgE, es-IgG4, and es-IgG1 of wheat proteins and determine the optimal peptides to differentiate wheat-allergic from wheat-tolerant using the bead-based epitope assay.

Methods: Children and adolescents who underwent an oral food challenge to confirm their wheat allergy status were enrolled.

CD23IgG1 memory B cells are poised to switch to pathogenic IgE production in food allergy.

Food allergy is caused by allergen-specific immunoglobulin E (IgE) antibodies, but little is known about the B cell memory of persistent IgE responses. Here, we describe, in human pediatric peanut allergy, a population of CD23IgG1 memory B cells arising in type 2 immune responses that contain high-affinity peanut-specific clones and generate IgE-producing cells upon activation. The frequency of CD23IgG1 memory B cells correlated with circulating concentrations of IgE in children with peanut allergy.

Epitope-Based IgE Assays and Their Role in Providing Diagnosis and Prognosis of Food Allergy.

With advances in molecular and computational science, epitope-specific IgE antibody profiling has been developed and recently brought into clinical practice. Epitope-based testing detects IgE antibodies that directly bind to antigenic sites of an allergen, providing increased resolution specificity and fewer false-positive results for diagnosing food allergy. Epitope-binding profiles may also serve as prognostic markers of food allergy and help predict quantities of allergen that would provoke a reaction (ie, eliciting dose, possible severity of a reaction after allergen ingestion, and outcomes of treatment options such as oral immunotherapy [OIT]).

A machine learning approach to determine resilience utilizing wearable device data: analysis of an observational cohort.

Objective: To assess whether an individual's degree of psychological resilience can be determined from physiological metrics passively collected from a wearable device.

Materials And Methods: Data were analyzed in this secondary analysis of the Warrior Watch Study dataset, a prospective cohort of healthcare workers enrolled across 7 hospitals in New York City. Subjects wore an Apple Watch for the duration of their participation.

Baroreflex sensitivity is associated with markers of hippocampal gliosis and dysmyelination in patients with psychosis.

Purpose: Hippocampal dysfunction plays a key role in the pathology of psychosis. Given hippocampal sensitivity to changes in cerebral perfusion, decreased baroreflex function could contribute to psychosis pathogenesis. This study had two aims: (1) To compare baroreflex sensitivity in participants with psychosis to two control groups: participants with a nonpsychotic affective disorder and participants with no history of psychiatric disease; (2) to examine the relationship between hippocampal neurometabolites and baroreflex sensitivities in these three groups.

Epitope-Specific IgE at 1 Year of Age Can Predict Peanut Allergy Status at 5 Years.

Background: Currently, there is no laboratory test that can accurately identify children at risk of developing peanut allergy. Utilizing a subset of children randomized to the peanut avoidance arm of the LEAP trial, we monitored the development of epitope-specific (ses-)IgE and ses-IgG4 from 4-11 months to 5 years of age.

Objective: The aim of the study was to evaluate the prognostic ability of epitope-specific antibodies to predict the result of an oral food challenge (OFC) at 5 years.

Predicting probability of tolerating discrete amounts of peanut protein in allergic children using epitope-specific IgE antibody profiling.

Background: IgE-epitope profiling can accurately diagnose clinical peanut allergy.

Objective: We sought to determine whether sequential (linear) epitope-specific IgE (ses-IgE) profiling can provide probabilities of tolerating discrete doses of peanut protein in allergic subjects undergoing double-blind, placebo-controlled food challenges utilizing PRACTALL dosing.

Methods: Sixty four ses-IgE antibodies were quantified in blood samples using a bead-based epitope assay.

Mapping Sequential IgE-Binding Epitopes on Major and Minor Egg Allergens.

Introduction: Molecular studies of hen's egg allergens help define allergic phenotypes, with IgE to sequential (linear) epitopes on the ovomucoid (OVM) protein associated with a persistent disease. Epitope profiles of other egg allergens are largely unknown. The objective of this study was to construct an epitope library spanning across 7 allergens and further evaluate sequential epitope-specific (ses-)IgE and ses-IgG4 among baked-egg reactive or tolerant children.

Environmental exposure unit simulates natural seasonal birch pollen exposures while maximizing change in allergic symptoms.

Background: Birch pollen is a prevalent aeroallergen during the springtime allergy season. In field studies, variable allergen exposure and environmental factors can affect data quality while environmental exposure units (EEUs) deliver controlled, standardized, and reproducible allergen exposures.

Objective: To inform study design for EEU trials evaluating antiallergic therapies.

Accurate and reproducible diagnosis of peanut allergy using epitope mapping.

Background: Accurate diagnosis of peanut allergy is a significant clinical challenge. Here, a novel diagnostic blood test using the peanut bead-based epitope assay ("peanut BBEA") was developed utilizing the LEAP cohort and then validated using two independent cohorts.

Methods: The development of the peanut BBEA diagnostic test followed the National Academy of Medicine's established guidelines with discovery performed on 133 subjects from the non-interventional arm of the LEAP trial and an independent validation performed on 82 subjects from the CoFAR2 and 84 subjects from the POISED study.

Evolution of epitope-specific IgE and IgG antibodies in children enrolled in the LEAP trial.

Background: In the LEAP (Learning Early About Peanut Allergy) trial, early consumption of peanut in high-risk infants was found to decrease the rate of peanut allergy at 5 years of age. Sequential epitope-specific (ses-)IgE is a promising biomarker of clinical peanut reactivity.

Objective: We sought to compare the evolution of ses-IgE and ses-IgG in children who developed (or not) peanut allergy and to evaluate the immunomodulatory effects of early peanut consumption on these antibodies.

bbeaR: an R package and framework for epitope-specific antibody profiling.

Summary: Analysis of epitope-specific antibody repertoires has provided novel insights into the pathogenesis of inflammatory disorders, especially allergies. A novel multiplex immunoassay, termed Bead-Based Epitope Assay (BBEA), was developed to quantify levels of epitope-specific immunoglobulins, including IgE, IgG, IgA and IgD isotypes. bbeaR is an open-source R package, developed for the BBEA, provides a framework to import, process and normalize .

Early epidemiological indicators, outcomes, and interventions of COVID-19 pandemic: A systematic review.

Background: Coronavirus disease-2019 (COVID-19), a pandemic that brought the whole world to a standstill, has led to financial and health care burden. We aimed to evaluate epidemiological characteristics, needs of resources, outcomes, and global burden of the disease.

Methods: Systematic review was performed searching PubMed from December 1, 2019, to March 25, 2020, for full-text observational studies that described epidemiological characteristics, following MOOSE protocol.

Intestinal Inflammation Modulates the Expression of ACE2 and TMPRSS2 and Potentially Overlaps With the Pathogenesis of SARS-CoV-2-related Disease.

Background And Aims: The presence of gastrointestinal symptoms and high levels of viral RNA in the stool suggest active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication within enterocytes.

Methods: Here, in multiple, large cohorts of patients with inflammatory bowel disease (IBD), we have studied the intersections between Coronavirus Disease 2019 (COVID-19), intestinal inflammation, and IBD treatment.

Results: A striking expression of ACE2 on the small bowel enterocyte brush border supports intestinal infectivity by SARS-CoV-2.

Early epitope-specific IgE antibodies are predictive of childhood peanut allergy.

Background: Peanut allergy is characterized by the development of IgE against peanut antigen.

Objective: We sought to evaluate the evolution of epitope-specific (es)IgE and esIgG in a prospective cohort of high-risk infants to determine whether antibody profiles can predict peanut allergy after age 4 years.

Methods: The end point was allergy status at age 4 years; samples from 293 children were collected at age 3 to 15 months and 2 to 3 and 4 years.

Ovomucoid epitope-specific repertoire of IgE, IgG , IgG , IgA , and IgD antibodies in egg-allergic children.

Background: Egg-white ovomucoid, that is, Gal d 1, is associated with IgE-mediated allergic reactions in most egg-allergic children. Epitope-specific IgE levels have been correlated with the severity of egg allergy, while emerging evidence suggests that other antibody isotypes (IgG , IgG , IgA, and IgD) may have a protective function; yet, their epitope-specific repertoires and associations with atopic comorbidities have not been studied.

Methods: Bead-based epitope assay (BBEA) was used to quantitate the levels of epitope-specific (es)IgA, esIgE, esIgD, esIgG , and esIgG antibodies directed at 58 (15-mer) overlapping peptides, covering the entire sequence of ovomucoid, in plasma of 38 egg-allergic and 6 atopic children.

Author Correction: Novel Bead-Based Epitope Assay is a sensitive and reliable tool for profiling epitope-specific antibody repertoire in food allergy.

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

Molecular and Cellular Responses to the TYK2/JAK1 Inhibitor PF-06700841 Reveal Reduction of Skin Inflammation in Plaque Psoriasis.

The IL-23/T helper type 17 cell axis is a target for psoriasis. The TYK2/Janus kinase 1 inhibitor PF-06700841 will directly suppress TYK2-dependent IL-12 and IL-23 signaling and Janus kinase 1-dependent signaling in cells expressing these signaling molecules, including T cells and keratinocytes. This clinical study sought to define the inflammatory gene and cellular pathways through which PF-06700841 improves the clinical manifestations of psoriasis.

Novel Bead-Based Epitope Assay is a sensitive and reliable tool for profiling epitope-specific antibody repertoire in food allergy.

Identification of allergenic IgE epitopes is instrumental for the development of novel diagnostic and prognostic methods in food allergy. In this work, we present the quantification and validation of a Bead-Based Epitope Assay (BBEA) that through multiplexing of epitopes and multiple sample processing enables completion of large experiments in a short period of time, using minimal quantities of patients' blood. Peptides that are uniquely coupled to beads are incubated with serum or plasma samples, and after a secondary fluorophore-labeled antibody is added, the level of fluorescence is quantified with a Luminex reader.