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Meri K Tulic - One of the best experts on this subject based on the ideXlab platform.
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a role for early oral exposure to house dust mite allergens through breast milk in ige mediated Food allergy susceptibility
The Journal of Allergy and Clinical Immunology, 2020Co-Authors: Akila Rekima, Chrystelle Bonnart, Patricia Macchiaverni, Jessica Metcalfe, Meri K Tulic, Nicolas Halloin, Samah Rekima, Jon GenuneitAbstract:Background Successful prevention of Food allergy requires the identification of the factors adversely affecting the capacity to develop oral tolerance to Food Antigen in early life. Objectives This study sought to determine whether oral exposure to Dermatophagoides pteronyssinus through breast milk affects gut mucosal immunity with long-term effects on IgE-mediated Food allergy susceptibility. Methods Gut immunity was explored in 2-week-old mice breast-fed by mothers exposed to D pteronyssinus, protease-inactivated D pteronyssinus, or to PBS during lactation. We further analyzed oral tolerance to a bystander Food allergen, ovalbumin (OVA). In a proof-of-concept study, Der p 1 and OVA levels were determined in 100 human breast milk samples and the association with prevalence of IgE-mediated egg allergy at 1 year was assessed. Results Increased permeability, IL-33 levels, type 2 innate lymphoid cell activation, and Th2 cell differentiation were found in gut mucosa of mice nursed by mothers exposed to D pteronyssinus compared with PBS. This pro-Th2 gut mucosal environment inhibited the induction of Antigen-specific FoxP3 regulatory T cells and the prevention of Food allergy by OVA exposure through breast milk. In contrast, protease-inactivated D pteronyssinus had no effect on offspring gut mucosal immunity. Based on the presence of Der p 1 and/or OVA in human breast milk, we identified groups of lactating mothers, which mirror the ones found in mice to be responsible for different egg allergy risk. Conclusions This study highlights an unpredicted potential risk factor for the development of Food allergy, that is, D pteronyssinus allergens in breast milk, which disrupt gut immune homeostasis and prevents oral tolerance induction to bystander Food Antigen through their protease activity.
Ludvig M Sollid - One of the best experts on this subject based on the ideXlab platform.
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the intestinal t cell response to α gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase
Journal of Experimental Medicine, 2000Co-Authors: Helene Arentzhansen, Roman Korner, Oyvind Molberg, Hanne Quarsten, Willemijn Vader, Y Kooy, Knut E A Lundin, Frits Koning, Peter Roepstorff, Ludvig M SollidAbstract:The great majority of patients that are intolerant of wheat gluten protein due to celiac disease (CD) are human histocompatibility leukocyte Antigen (HLA)-DQ2+, and the remaining few normally express HLA-DQ8. These two class II molecules are chiefly responsible for the presentation of gluten peptides to the gluten-specific T cells that are found only in the gut of CD patients but not of controls. Interestingly, tissue transglutaminase (tTG)-mediated deamidation of gliadin plays an important role in recognition of this Food Antigen by intestinal T cells. Here we have used recombinant Antigens to demonstrate that the intestinal T cell response to α-gliadin in adult CD is focused on two immunodominant, DQ2-restricted peptides that overlap by a seven-residue fragment of gliadin. We show that tTG converts a glutamine residue within this fragment into glutamic acid and that this process is critical for T cell recognition. Gluten-specific T cell lines from 16 different adult patients all responded to one or both of these deamidated peptides, indicating that these epitopes are highly relevant to disease pathology. Binding studies showed that the deamidated peptides displayed an increased affinity for DQ2, a molecule known to preferentially bind peptides containing negatively charged residues. Interestingly, the modified glutamine is accommodated in different pockets of DQ2 for the different epitopes. These results suggest modifications of anchor residues that lead to an improved affinity for major histocompatibility complex (MHC), and altered conformation of the peptide–MHC complex may be a critical factor leading to T cell responses to gliadin and the oral intolerance of gluten found in CD.
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the intestinal t cell response to alpha gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase
Journal of Experimental Medicine, 2000Co-Authors: Helene Arentzhansen, Roman Korner, Oyvind Molberg, Hanne Quarsten, Willemijn Vader, Y Kooy, Knut E A Lundin, Frits Koning, Peter Roepstorff, Ludvig M SollidAbstract:The great majority of patients that are intolerant of wheat gluten protein due to celiac disease (CD) are human histocompatibility leukocyte Antigen (HLA)-DQ2(+), and the remaining few normally express HLA-DQ8. These two class II molecules are chiefly responsible for the presentation of gluten peptides to the gluten-specific T cells that are found only in the gut of CD patients but not of controls. Interestingly, tissue transglutaminase (tTG)-mediated deamidation of gliadin plays an important role in recognition of this Food Antigen by intestinal T cells. Here we have used recombinant Antigens to demonstrate that the intestinal T cell response to alpha-gliadin in adult CD is focused on two immunodominant, DQ2-restricted peptides that overlap by a seven-residue fragment of gliadin. We show that tTG converts a glutamine residue within this fragment into glutamic acid and that this process is critical for T cell recognition. Gluten-specific T cell lines from 16 different adult patients all responded to one or both of these deamidated peptides, indicating that these epitopes are highly relevant to disease pathology. Binding studies showed that the deamidated peptides displayed an increased affinity for DQ2, a molecule known to preferentially bind peptides containing negatively charged residues. Interestingly, the modified glutamine is accommodated in different pockets of DQ2 for the different epitopes. These results suggest modifications of anchor residues that lead to an improved affinity for major histocompatibility complex (MHC), and altered conformation of the peptide-MHC complex may be a critical factor leading to T cell responses to gliadin and the oral intolerance of gluten found in CD.
Jon Genuneit - One of the best experts on this subject based on the ideXlab platform.
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a role for early oral exposure to house dust mite allergens through breast milk in ige mediated Food allergy susceptibility
The Journal of Allergy and Clinical Immunology, 2020Co-Authors: Akila Rekima, Chrystelle Bonnart, Patricia Macchiaverni, Jessica Metcalfe, Meri K Tulic, Nicolas Halloin, Samah Rekima, Jon GenuneitAbstract:Background Successful prevention of Food allergy requires the identification of the factors adversely affecting the capacity to develop oral tolerance to Food Antigen in early life. Objectives This study sought to determine whether oral exposure to Dermatophagoides pteronyssinus through breast milk affects gut mucosal immunity with long-term effects on IgE-mediated Food allergy susceptibility. Methods Gut immunity was explored in 2-week-old mice breast-fed by mothers exposed to D pteronyssinus, protease-inactivated D pteronyssinus, or to PBS during lactation. We further analyzed oral tolerance to a bystander Food allergen, ovalbumin (OVA). In a proof-of-concept study, Der p 1 and OVA levels were determined in 100 human breast milk samples and the association with prevalence of IgE-mediated egg allergy at 1 year was assessed. Results Increased permeability, IL-33 levels, type 2 innate lymphoid cell activation, and Th2 cell differentiation were found in gut mucosa of mice nursed by mothers exposed to D pteronyssinus compared with PBS. This pro-Th2 gut mucosal environment inhibited the induction of Antigen-specific FoxP3 regulatory T cells and the prevention of Food allergy by OVA exposure through breast milk. In contrast, protease-inactivated D pteronyssinus had no effect on offspring gut mucosal immunity. Based on the presence of Der p 1 and/or OVA in human breast milk, we identified groups of lactating mothers, which mirror the ones found in mice to be responsible for different egg allergy risk. Conclusions This study highlights an unpredicted potential risk factor for the development of Food allergy, that is, D pteronyssinus allergens in breast milk, which disrupt gut immune homeostasis and prevents oral tolerance induction to bystander Food Antigen through their protease activity.
Jonathan M Spergel - One of the best experts on this subject based on the ideXlab platform.
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Eosinophilic Esophagitis and Gastroenteritis
Current Allergy and Asthma Reports, 2015Co-Authors: Antonella Cianferoni, Jonathan M SpergelAbstract:Eosinophilic gastrointestinal disease (EGID) can be classified as eosinophilic esophagitis (EoE) when the eosinophilia is limited to the esophagus or as eosinophilic gastritis (EG) if it is limited to the gastric tract, eosinophilic colitis (EC) if it is limited to the colon, and eosinophilic gastroenteritis (EGE) if the eosinophilia involves one or more parts of the gastrointestinal tract. EoE is by far the most common EGID. It is a well-defined chronic atopic disease due to a T helper type 2 (Th2) inflammation triggered often by Food allergens. EoE diagnosis is done if an esophageal biopsy shows at least 15 eosinophils per high power field (eos/hpf). Globally accepted long-term therapies for EoE are the use of swallowed inhaled steroids or Food Antigen avoidance. The treatment of EoE is done not only to control symptoms but also to prevent complications such as esophageal stricture and Food impaction. EGE cause non-specific gastrointestinal (GI) symptoms and are diagnosed if esophagogastroduodenoscopy (EGD)/colonoscopy show eosinophilia in one or more parts of the GI tract. They are rare diseases with an unclear pathogenesis, and they are poorly defined in terms of diagnostic criteria and treatment. Before initiating treatment of any EGE, it is imperative to conduct a differential diagnosis to exclude other causes of hypereosinophilia with GI localization. EGE are often poorly responsive to therapy and there is no commonly accepted long-term treatment. EG has many characteristics similar to EoE, including the fact that it is often due to a Food allergen-driven Th2 inflammation; transcriptome analysis however shows that it is more a systemic disease and has a different gene signature than EoE. EC is a benign form of delayed Food allergy in infant and is instead a difficult-to-treat severe inflammatory condition in older children and adults. EC in the latter groups can be a manifestation of drug allergy or autoimmune disease. Overall EGE, EC, and EG are rare and are a diagnosis of exclusion until more common causes of eosinophilia have been excluded.
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identification of causative Foods in children with eosinophilic esophagitis treated with an elimination diet
The Journal of Allergy and Clinical Immunology, 2012Co-Authors: Jonathan M Spergel, Terri F Brownwhitehorn, Antonella Cianferoni, Michele Shuker, Meilun Wang, Ritu VermaAbstract:Background Eosinophilic esophagitis (EoE) is a chronic inflammatory disease with isolated eosinophils in the esophagus predominantly triggered by Foods. The optimal testing to identify inciting Foods remains unclear. Objectives We sought to determine the effectiveness of allergy testing-directed diets in patients with EoE. Methods A retrospective analysis of all children with EoE seen at the Children's Hospital of Philadelphia between 2000 and 2011 identified 941 patients with EoE. Skin prick tests (SPTs) and atopy patch tests (APTs) were conducted, and predictive values were calculated. IgE-mediated Food reactions were also identified. A Food was considered to cause EoE if its elimination led to resolution of esophageal eosinophilia or reintroduction led to reoccurrence of EoE. The effectiveness of the various elimination diets was compared with targeted Food Antigen elimination. Results Definitive Foods causing EoE were identified, with milk, egg, wheat, and soy as the most common Foods in 319 patients. IgE-mediated reactions (urticaria and anaphylaxis) were seen in 15%. The negative predictive value for the combination of SPTs and APTs averaged 92%, with the exception of milk at 44%, and the positive predictive value averaged 44%. An empiric 6-Food elimination diet or removal of positive Foods on allergy testing (SPTs/APTs) both had a histologic success rate of 53%. Removal of Foods identified on SPTs/APTs plus empiric elimination of milk leads to resolution in 77% of patients. Conclusion An elimination diet based on SPT/APT results leads to resolution of esophageal eosinophilia in a similar proportion of patients as empiric removal of Foods but required that fewer Foods be removed. These observations suggest that both methods are acceptable options.
Helene Arentzhansen - One of the best experts on this subject based on the ideXlab platform.
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the intestinal t cell response to α gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase
Journal of Experimental Medicine, 2000Co-Authors: Helene Arentzhansen, Roman Korner, Oyvind Molberg, Hanne Quarsten, Willemijn Vader, Y Kooy, Knut E A Lundin, Frits Koning, Peter Roepstorff, Ludvig M SollidAbstract:The great majority of patients that are intolerant of wheat gluten protein due to celiac disease (CD) are human histocompatibility leukocyte Antigen (HLA)-DQ2+, and the remaining few normally express HLA-DQ8. These two class II molecules are chiefly responsible for the presentation of gluten peptides to the gluten-specific T cells that are found only in the gut of CD patients but not of controls. Interestingly, tissue transglutaminase (tTG)-mediated deamidation of gliadin plays an important role in recognition of this Food Antigen by intestinal T cells. Here we have used recombinant Antigens to demonstrate that the intestinal T cell response to α-gliadin in adult CD is focused on two immunodominant, DQ2-restricted peptides that overlap by a seven-residue fragment of gliadin. We show that tTG converts a glutamine residue within this fragment into glutamic acid and that this process is critical for T cell recognition. Gluten-specific T cell lines from 16 different adult patients all responded to one or both of these deamidated peptides, indicating that these epitopes are highly relevant to disease pathology. Binding studies showed that the deamidated peptides displayed an increased affinity for DQ2, a molecule known to preferentially bind peptides containing negatively charged residues. Interestingly, the modified glutamine is accommodated in different pockets of DQ2 for the different epitopes. These results suggest modifications of anchor residues that lead to an improved affinity for major histocompatibility complex (MHC), and altered conformation of the peptide–MHC complex may be a critical factor leading to T cell responses to gliadin and the oral intolerance of gluten found in CD.
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the intestinal t cell response to alpha gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase
Journal of Experimental Medicine, 2000Co-Authors: Helene Arentzhansen, Roman Korner, Oyvind Molberg, Hanne Quarsten, Willemijn Vader, Y Kooy, Knut E A Lundin, Frits Koning, Peter Roepstorff, Ludvig M SollidAbstract:The great majority of patients that are intolerant of wheat gluten protein due to celiac disease (CD) are human histocompatibility leukocyte Antigen (HLA)-DQ2(+), and the remaining few normally express HLA-DQ8. These two class II molecules are chiefly responsible for the presentation of gluten peptides to the gluten-specific T cells that are found only in the gut of CD patients but not of controls. Interestingly, tissue transglutaminase (tTG)-mediated deamidation of gliadin plays an important role in recognition of this Food Antigen by intestinal T cells. Here we have used recombinant Antigens to demonstrate that the intestinal T cell response to alpha-gliadin in adult CD is focused on two immunodominant, DQ2-restricted peptides that overlap by a seven-residue fragment of gliadin. We show that tTG converts a glutamine residue within this fragment into glutamic acid and that this process is critical for T cell recognition. Gluten-specific T cell lines from 16 different adult patients all responded to one or both of these deamidated peptides, indicating that these epitopes are highly relevant to disease pathology. Binding studies showed that the deamidated peptides displayed an increased affinity for DQ2, a molecule known to preferentially bind peptides containing negatively charged residues. Interestingly, the modified glutamine is accommodated in different pockets of DQ2 for the different epitopes. These results suggest modifications of anchor residues that lead to an improved affinity for major histocompatibility complex (MHC), and altered conformation of the peptide-MHC complex may be a critical factor leading to T cell responses to gliadin and the oral intolerance of gluten found in CD.