IL-9 is a key component of memory TH cell peanut-specific responses from children with peanut allergy

Brough, Helen A.; Cousins, David J.; Munteanu, Alina; Wong, Yuen Fei; Sudra, Asha; Makinson, Kerry; Stephens, Alick; Arno, Matthew; Ciortuz, Liviu; Lack, Gideon; Turcanu, Victor

doi:10.1016/j.jaci.2014.06.032

Cited by 89 publications

(68 citation statements)

References 53 publications

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“…A more recent publication from the same group defined IL-9 as a potential marker differentiating between peanut-sensitized and peanutallergic individuals at an allergen-specific T-cell level. They demonstrated a significant upregulation of this cytokine among other TH2-type cytokines in peanut-specific activated gut and skin homing memory T-cell populations (127). This finding corresponds with data from peanut-stimulated PBMCs (128).…”

Section: Oral and Sublingual Immunotherapy In Food Allergysupporting

confidence: 78%

Markers of tolerance development to food allergens

Ponce

Diesner

Szépfalusi

et al. 2016

Allergy

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IgE-mediated reactions to food allergens are the most common cause of anaphylaxis in childhood. Although allergies to cow's milk, egg, or soy proteins, in contrast to peanut and tree nut allergens, resolve within the first 6 years of life in up to 60% due to natural tolerance development, this process is not well understood. At present, there is no cure or treatment for food allergy that would result in an induction of tolerance to the symptom-eliciting food. Avoidance, providing an emergency plan and education, is the standard of treatment. Oral immunotherapeutic approaches have been proven reasonable efficacy; however, they are associated with high rates of side-effects and low numbers of patients achieving tolerance. Nevertheless, mechanisms that take place during oral immunotherapy may help to understand tolerance development. On the basis of these therapeutic interventions, events like loss of basophil activation and induction of regulatory lymphocyte subsets and of blocking antibodies have been described. Their functional importance at a clinical level, however, remains to be investigated in detail. Consequently, there is eminent need to understand the process of tolerance development to food allergens and define biomarkers to develop and monitor new treatment strategies for food allergy.IgE-mediated food allergy represents the most important cause of anaphylaxis in childhood. While milk and egg allergy are associated with a high rate of natural tolerance development within the first 6 years of life, this is less clear for other food allergies. Consequently, once it is communicated the diagnosis persists often lifelong severely impacting the quality of life of the patient and the environment despite the recommendation to reconsider clinical tolerance development from time to time.Currently, avoidance, providing an emergency plan and teaching, is the standard of treatment; however, there is no cure or treatment that has reached the level of recommendation to re-induce tolerance to the symptom-eliciting food. Tolerance assessment occurs either via oral food challenges or due to unintended exposure. Given the cost and time intensiveness of oral food challenges and its potential harmfulness, there is eminent need to understand the process of tolerance development and define markers thereof to develop and monitor new treatment strategies for food allergy. This review aimed to provide an overview on recent advances regarding markers and mechanisms of tolerance development to food allergens.Oral tolerance in the context of food allergy is considered to occur if the antigen/food can be ingested without problems despite prolonged periods of avoidance, while the status of desensitization is strictly dependent on regular ingestion of the respective food in order to confer protection from allergic reactions. Currently, there is no general consensus on the exact time frame of avoidance and re-exposure that would allow the usage of the terminus tolerance that is considered equivalent to cure in the context of or...

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Section: Oral and Sublingual Immunotherapy In Food Allergysupporting

confidence: 78%

Markers of tolerance development to food allergens

Ponce

Diesner

Szépfalusi

et al. 2016

Allergy

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“…Downregulated genes predominantly encode lysosomal and endosomal enzymes and scavenger receptors. The observed upregulation of IL-9, IL-5, CEAMCAM1, and CISH was consistent with another published report of gene expression from purified peanut-responsive CD4+ T cells from peanut allergic individuals [12]. Thus we were able to detect a gene signature consistent with allergen-specific CD4+ T cells using bulk PBMC microarray.…”

Section: Resultssupporting

confidence: 92%

Transcriptional Profiling of Egg Allergy and Relationship to Disease Phenotype

et al. 2016

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BackgroundEgg 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.ObjectiveTo use transcriptional profiling as a novel approach to uncover immunologic processes associated with different phenotypes of egg allergy.MethodsPeripheral blood mononuclear cells (PBMCs) were obtained from egg-allergic children who were defined as reactive (BER) or tolerant (BET) to baked egg, and from food allergic controls (AC) who were egg non-allergic. PBMCs were stimulated with egg white protein. Gene transcription was measured by microarray after 24 h, and cytokine secretion by multiplex assay after 5 days.ResultsThe transcriptional response of PBMCs to egg protein differed between BER and BET versus AC subjects. Compared to the AC group, the BER group displayed increased expression of genes associated with allergic inflammation as well as corresponding increased secretion of IL-5, IL-9 and TNF-α. A similar pattern was observed for the BET group. Further similarities in gene expression patterns between BER and BET groups, as well as some important differences, were revealed using a novel Immune Annotation resource developed for this project. This approach identified several novel processes not previously associated with egg allergy, including positive associations with TLR4-stimulated myeloid cells and activated NK cells, and negative associations with an induced Treg signature. Further pathway analysis of differentially expressed genes comparing BER to BET subjects showed significant enrichment of IFN-α and IFN-γ response genes, as well as genes associated with virally-infected DCs.ConclusionsTranscriptional profiling identified several novel pathways and processes that differed when comparing the response to egg allergen in BET, BER, and AC groups. We conclude that this approach is a useful hypothesis-generating mechanism to identify novel immune processes associated with allergy and tolerance to forms of egg.

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“…Upon food allergen, but not nonspecific stimulation, peripheral blood mononuclear cells from EoE patients with or without allergen-specific IgE produce significant amounts of IL-5 (48). In peanut-allergic children, skin-and gut-homing T cells expressing Th2 and Th9 genes as well as IL-9 and IL-5 production by distinct T helper cell populations have been reported (49).…”

Section: Food-specific T-cell Responses In the Skinmentioning

confidence: 99%

Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity

Simon

Cianferoni

Spergel

et al. 2016

Allergy

205

130

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Eosinophilic esophagitis (EoE) is a chronic disease characterized clinically by symptoms of esophageal dysfunction and histologically by eosinophil-predominant inflammation. EoE is frequently associated with concomitant atopic diseases and immunoglobulin E (IgE) sensitization to food allergens in children as well as to aeroallergens and cross-reactive plant allergen components in adults. Patients with EoE respond well to elemental and empirical food elimination diets. Recent research has, however, indicated that the pathogenesis of EoE is distinct from IgE-mediated food allergy. In this review, we discuss the individual roles of epithelial barrier defects, dysregulated innate and adaptive immune responses, and of microbiota in the pathogenesis of EoE. Although food has been recognized as a trigger factor of EoE, the mechanism by which it initiates or facilitates eosinophilic inflammation appears to be largely independent of IgE and needs to be further investigated. Understanding the pathogenic role of food in EoE is a prerequisite for the development of specific diagnostic tools and targeted therapeutic procedures.Abbreviations ACD, allergic contact dermatitis; AD, atopic dermatitis; APT, atopy patch test; DHR, drug hypersensitivity reactions; EoE, eosinophilic esophagitis; FPIES, food protein-induced enterocolitis; GERD, gastroesophageal reflux disease; GI, gastrointestinal; IBD, inflammatory bowel disease; Ig, immunoglobulin; OAS, oral allergy syndrome; PPI-REE, proton pump inhibitor-responsive esophageal eosinophilia; SFED, six-food elimination diet; SPT, skin prick test; TCR, T-cell receptor; TNF, tumor necrosis factor.Allergy 71 (2016) 611-620

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IL-9 is a key component of memory TH cell peanut-specific responses from children with peanut allergy

Cited by 89 publications

References 53 publications

Markers of tolerance development to food allergens

Markers of tolerance development to food allergens

Transcriptional Profiling of Egg Allergy and Relationship to Disease Phenotype

Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity

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