BackgroundThe oligosaccharide galactose‐α‐1,3‐galactose (α‐Gal), present in mammalian proteins and lipids, causes an unusual delayed allergic reaction 3 to 6 hours after ingestion of mammalian meat in individuals with IgE antibodies against α‐Gal. To better understand the delayed onset of allergic symptoms and investigate whether protein‐bound or lipid‐bound α‐Gal causes these symptoms, we analyzed the capacity of α‐Gal conjugated proteins and lipids to cross a monolayer of intestinal cells.MethodsExtracts of proteins and lipids from beef were prepared, subjected to in vitro digestions, and added to Caco‐2 cells grown on permeable supports. The presence of α‐Gal in the basolateral medium was investigated by immunoblotting, thin‐layer chromatography with immunostaining and ELISA, and its allergenic activity was analyzed in a basophil activation test.ResultsAfter addition of beef proteins to the apical side of Caco‐2 cells, α‐Gal containing peptides were not detected in the basolateral medium. Those peptides that crossed the Caco‐2 monolayer did not activate basophils from an α‐Gal allergic patient. Instead, when Caco‐2 cells were incubated with lipids extracted from beef, α‐Gal was detected in the basolateral medium. Furthermore, these α‐Gal lipids were able to activate the basophils of an α‐Gal allergic patient in a dose‐dependent manner.ConclusionOnly α‐Gal bound to lipids, but not to proteins, is able to cross the intestinal monolayer and trigger an allergic reaction. This suggests that the slower digestion and absorption of lipids might be responsible for the unusual delayed allergic reactions in α‐Gal allergic patients and identifies glycolipids as potential allergenic molecules.

Background: Peanut and tree nut allergies are the most important causes of anaphylaxis. Co-reactivity to more than one nut is frequent, and co-sensitization in the absence of clinical data is often obtained. Confirmatory oral food challenges (OFCs) are inconsistently performed.Objective: To investigate the utility of the basophil activation test (BAT) in diagnosing peanut and tree nut allergies. Methods:The Markers Of Nut Allergy Study (MONAS) prospectively enrolled patients aged 0.5-17 years with confirmed peanut and/or tree nut (almond, cashew, hazelnut, pistachio, walnut) allergy or sensitization from Canadian (n = 150) and Austrian (n = 50) tertiary pediatric centers. BAT using %CD63 + basophils (SSClow/CCR3pos) as outcome was performed with whole blood samples stimulated with allergen extracts of each nut (0.001-1000 ng/mL protein). BAT results were assessed against confirmed | 1801 DUAN et Al.

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...

Author contributions: M.P. took care of the sample preparation, selection of patients according to inclusion criteria, contributed to the design of the arrays, selection of allergens, analysis of data and interpretation of the results and writing of the manuscript. F.S. processed the experimental data and did statistical analysis and R.S. contributed to prepare the samples, Accepted Article This article is protected by copyright. All rights reserved. IgG purification and subsequent quantification, to the processing of the experimental data and contributed to the methods section of the manuscript. K.S. contributed to sample collection and preparation and selection of patients according to inclusion criteria. K. L.B. and C.S.H. helped in the design and analysis and interpretation of the peptide chip. C.B. was involved in the clinical trial and provided the clinical data Z.S. as PI served responsible for design, conduction of the clinical trial, provided the samples. A.W. contributed to the design of the study, design of arrays, analysis of data and interpretation of the results. S.W. provided the draft genome of Dermatophagoides farinae. T.E. and Z.S. conceived the present idea and T.E. designed the study, contributed to manuscript´s generation and was involved in data analysis and supervised the whole project.

Food allergy is the major reason for severe anaphylaxis in childhood and adolescence. Currently, effective and safe treatments for food allergy are unavailable. Allergen-specific CD4 T cells have a pivotal role in causing and maintaining the allergic response to food allergens. The purpose of this review is to provide an overview on the role of allergen-specific T cells in food allergy during allergic sensitization, natural tolerance development and allergen immunotherapy. Allergen-specific T cells in the context of food allergy are predominantly of a Th2 type with slightly different surface marker expression patterns in different food allergies. During the process of reverting food allergy to a status of tolerance or sustained unresponsiveness there is a loss of this Th2 committed compartment with an asymptotic approximation to a regulatory and Th0/Th1 dominated compartment seen in non-allergic individuals. This process is accompanied by a significant reduction of absolute frequencies of allergen-specific T cells. Particularly, regulatory T cells may provide significant help to achieve sustained control of the effector cell populations via suppression of effector cell function and possibly induction of blocking antibodies.