B cells in human food allergy have been studied predominantly in the blood. Little is known about IgE+ B cells or plasma cells in tissues exposed to dietary antigens. We characterized IgE+ clones in blood, stomach, duodenum, and esophagus of 19 peanut-allergic patients, using high-throughput DNA sequencing. IgE+ cells in allergic patients are enriched in stomach and duodenum, and have a plasma cell phenotype. Clonally related IgE+ and non-IgE–expressing cell frequencies in tissues suggest local isotype switching, including transitions between IgA and IgE isotypes. Highly similar antibody sequences specific for peanut allergen Ara h 2 are shared between patients, indicating that common immunoglobulin genetic rearrangements may contribute to pathogenesis. These data define the gastrointestinal tract as a reservoir of IgE+ B lineage cells in food allergy.
Background Thirty percent of children with food allergies have multiple simultaneous allergies, however, the features of these multiple allergies are not well characterized serologically or clinically. Objective We comprehensively evaluated 60 multi-allergic patients by measuring serum IgE to key allergen components, evaluating clinical histories and medication use, performing skin tests, and conducting double-blind, placebo-controlled food challenges (DBPCFCs). Methods Sixty participants with multiple food allergies were characterized by clinical history, DBPCFCs, total IgE, sIgE, and component resolved diagnostics (IgE and IgG4) data. The food allergens tested were almond, egg, milk, sesame, peanut, pecan, walnut, hazelnut, cashew, pistachio, soy and wheat. Results Our data demonstrate that of the reactions observed during a graded DBPCFC, gastrointestinal reactions occurred more often in boys than in girls, as well as in individuals with high levels of IgE to 2S albumins from cashew, walnut and hazelnut. Certain food allergies often occurred concomitantly in individuals (i.e., cashew/pistachio and walnut/pecan/hazelnut). IgE testing to components further corroborated serological relationships between and among these clustered food allergies. Conclusions Associations of certain food allergies was shown by DBPCFC outcomes as well as by correlations in IgE reactivity to structurally related food allergen components. Each of these criteria independently demonstrated a significant association between allergies to cashew and pistachio, as well as among allergies to walnut, pecan and hazelnut.
Aging is intimately linked to system‐wide metabolic changes that can be captured in blood. Understanding biological processes of aging in humans could help maintain a healthy aging trajectory and promote longevity. We performed untargeted plasma metabolomics quantifying 770 metabolites on a cross‐sectional cohort of 268 healthy individuals including 125 twin pairs covering human lifespan (from 6 months to 82 years). Unsupervised clustering of metabolic profiles revealed 6 main aging trajectories throughout life that were associated with key metabolic pathways such as progestin steroids, xanthine metabolism, and long‐chain fatty acids. A random forest (RF) model was successful to predict age in adult subjects (≥16 years) using 52 metabolites (R2 = .97). Another RF model selected 54 metabolites to classify pediatric and adult participants (out‐of‐bag error = 8.58%). These RF models in combination with correlation network analysis were used to explore biological processes of healthy aging. The models highlighted established metabolites, like steroids, amino acids, and free fatty acids as well as novel metabolites and pathways. Finally, we show that metabolic profiles of twins become more dissimilar with age which provides insights into nongenetic age‐related variability in metabolic profiles in response to environmental exposure.
BackgroundA number of clinical studies focused on treating a single food allergy through oral immunotherapy (OIT) with adjunctive omalizumab treatment have been published. We previously demonstrated safety and tolerability of a rapid OIT protocol using omalizumab in a phase 1 study to achieve desensitization to multiple (up to 5) food allergens in parallel, rapidly (7–36 weeks; median = 18 weeks). In the current long-term, observational study, we followed 34 food allergic participants for over 5 years, who had originally undergone the phase 1 rapid OIT protocol.MethodsAfter reaching the maintenance dose of 2 g protein for each of their respective food allergens as a part of the phase 1 study, the long-term maintenance dose was reduced for some participants based on a pragmatic team-based decision. Participants were followed up to 62 months through standard oral food challenges (OFCs), skin prick tests, and blood tests.ResultsEach participant passed the 2 g OFC to each of their offending food allergens (up to 5 food allergens in total) at the end of the long-term follow-up (LTFU) study.ConclusionOur data demonstrate the feasibility of long-term maintenance dosing of a food allergen without compromising the desensitized status conferred through rapid-OIT. Trial registration Registry: Clinicaltrials.gov. Registration numbers: NCT01510626 (original study), NCT03234764 (LTFU study). Date of registration: November 29, 2011 (original study); July 26, 2017 (LTFU study, retrospectively registered)Electronic supplementary materialThe online version of this article (10.1186/s13223-017-0223-8) contains supplementary material, which is available to authorized users.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.