A multi‐centre study of candidate genes for wheeze and allergy: the International Study of Asthma and Allergies in Childhood Phase 2

Genuneit, Jon; Cantelmo, JL; Weinmayr, Gudrun; Wong, Gary; Cooper, Philip J.; Riikjärv, Mall-Anne; Gotua, Maia; Kabesch, Michael; Mutius, Erika von; Forastiére, Francesco; Crane, Julian; Nystad, Wenche; Sharif, Nuha El; Batllés-Garrido, J.; García‐Marcos, Luis; García‐Hernández, Gloria; Morales-Suárez-Varela, María; Nilsson, Lennart; Bråbäck, Lennart; Saraçlar, Y; Weiland, Stephan K.; Cookson, William; Strachan, D P; Moffatt, Miriam F.

doi:10.1111/j.1365-2222.2009.03364.x

Cited by 55 publications

(40 citation statements)

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“…if one parent is atopic there is a 20-40 % probability of a child developing this condition and, if both parents are atopic, a 50-80 % probability). Epidemiological studies are identifying genes involved in atopic predisposition (Walley et al, 2001;Weidinger et al, 2008;Genuneit et al, 2009). For example, filaggrin gene defects have recently been identified as a major risk factor for the development of atopic dermatitis.…”

Section: Atopic Dermatitismentioning

confidence: 99%

Scientific Opinion on the evaluation of allergenic foods and food ingredients for labelling purposes

Products¹

2014

EFS2

117

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Following a request from the Food Safety Authority of Ireland, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA Panel) was asked to deliver a scientific opinion on the evaluation of allergenic foods and food ingredients for labelling purposes. In view of the request, the NDA Panel decided to update its previous opinions relative to food ingredients or substances with known allergenic potential listed in Annex IIIa of 2003/89/EC, as amended. These include cereals containing gluten, milk and dairy products, eggs, nuts, peanuts, soy, fish, crustaceans, molluscs, celery, lupin, sesame, mustard and sulphites. The opinion relates to immunoglobulin (Ig)E-and non-IgE-mediated food allergy, to coeliac disease and to adverse reactions to sulphites in food, and it does not address non-immune-mediated adverse reactions to food. It includes information on the prevalence of food allergy in unselected populations, proteins identified as food allergens, cross-reactivities, the effects of food processing on the allergenicity of foods and ingredients, methods for the detection of allergens and allergenic foods, doses observed to trigger adverse reactions in sensitive individuals and risk assessment methodologies that have been used to derive individual and population thresholds for selected allergenic foods. The present opinion relates to immunoglobulin (Ig)E-and non-IgE-mediated food allergy, to coeliac disease and to adverse reactions to sulphites in food, and it does not address non-immune-mediated adverse reactions to food. For each food ingredient or substance listed in Annex IIIa, it includes information on the prevalence of food allergy in unselected populations, on proteins identified as food allergens, on cross-reactivities, on the effects of food processing on the allergenicity of foods and ingredients, on methods for the detection of allergens and allergenic foods, and on doses observed to trigger adverse reactions in sensitive individuals.Immune-mediated adverse reactions to foods manifest with clinical signs and symptoms of variable severity and duration, which may affect different organs and systems. Anaphylactic reactions to food are IgE mediated and may occur at any age. Non-IgE-mediated food allergy includes a wide range of diseases, including protein-induced enterocolitis and eosinophilic oesophagitis.A careful family and clinical history are the basis for diagnosis of food allergy. Food diaries, skin prick tests (SPTs), allergen-specific IgE measurements, food elimination diets and food challenges are part of the standard protocol for the diagnosis of food allergy. A positive SPT indicates sensitisation to the tested food, but it is not diagnostic of food allergy. Allergen-specific serum IgE antibodies similarly denote sensitisation to a particular food, but they are not diagnostic without a clinical history or food challenge. The use of atopy patch tests for the diagnosis of food allergy is controversial. Other available tests have no current role in the diagnosis of food allergy. Diag...

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Section: Atopic Dermatitismentioning

confidence: 99%

Scientific Opinion on the evaluation of allergenic foods and food ingredients for labelling purposes

Products¹

2014

EFS2

117

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“…AR is an inflammatory disease of the nasal mucosa induced by an immunoglobulin E (Helbling et al, 2014)-mediated reaction in allergen-sensitized individuals. It has been reported that numerous loci and candidate genes show an association with AR (Gaddam et al, 2012;Genuneit et al, 2009;Ibrahim et al, 2012;Tomazic et al, 2014). In spite of that, the molecular mechanisms underlying the development of AR have not been completely determined.…”

Section: Introductionmentioning

confidence: 95%

IL-23, rather than IL-17, is crucial for the development of ovalbumin-induced allergic rhinitis

Guo

Chen

2015

Molecular Immunology

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“…Allergic inflammation is characterized by airway hyperreactivity, type 2 cytokines (IL-4, -5, and -13), IgE, and the overproduction of mucus in the lung (1)(2)(3). Macrophages present at the site of allergic inflammation can be polarized by Th2-cytokines to become "alternatively activated" or M2 macrophages.…”

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confidence: 99%

The TORC1-activated Proteins, p70S6K and GRB10, Regulate IL-4 Signaling and M2 Macrophage Polarization by Modulating Phosphorylation of Insulin Receptor Substrate-2

Warren

Fang

Gowda

et al. 2016

Journal of Biological Chemistry

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Edited by Luke O'NeillLung M2 macrophages are regulators of airway inflammation, associated with poor lung function in allergic asthma. Previously, we demonstrated that IL-4-induced M2 gene expression correlated with tyrosine phosphorylation of the insulin receptor substrate-2 (IRS-2) in macrophages. We hypothesized that negative regulation of IRS-2 activity after IL-4 stimulation is dependent upon serine phosphorylation of IRS-2. Herein, we describe an inverse relationship between tyrosine phosphorylation (Tyr(P)) and serine phosphorylation (Ser(P)) of IRS-2 after IL-4 stimulation. Inhibiting serine phosphatase activity increased Ser(P)-IRS-2 and decreased Tyr(P)-IRS-2 leading to reduced M2 gene expression (CD200R, CCL22, MMP12, and TGM2). We found that inhibition of p70S6K, downstream of TORC1, resulted in diminished Ser(P)-IRS-2 and prolonged Tyr(P)-IRS-2 as well. Inhibition of p70S6K increased expression of CD200R and CCL22 indicating that p70S6K negatively regulates some, but not all, human M2 genes. Knocking down GRB10, another negative regulatory protein downstream of TORC1, enhanced both Tyr(P)-IRS-2 and increased expression of all four M2 genes. Furthermore, GRB10 associated with IRS-2, NEDD4.2 (an E3-ubiquitin ligase), IL-4R␣, and ␥C after IL-4 stimulation. Both IL-4R␣ and ␥C were ubiquitinated after 30 min of IL-4 treatment, suggesting that GRB10 may regulate degradation of the IL-4 receptor-signaling complex through interactions with NEDD4.2. Taken together, these data highlight two novel regulatory proteins that could be therapeutically manipulated to limit IL-4-induced IRS-2 signaling and polarization of M2 macrophages in allergic inflammation.Both genetic and environmental factors influence the onset and exacerbation of allergic asthma, which remains one of the most costly, non-communicable diseases of the human population. Allergic inflammation is characterized by airway hyperreactivity, type 2 cytokines (IL-4, -5, and -13), IgE, and the overproduction of mucus in the lung (1-3). Macrophages present at the site of allergic inflammation can be polarized by Th2-cytokines to become "alternatively activated" or M2 macrophages. In addition, the abundance of M2 macrophages in the lungs of asthmatics correlates with symptom severity (4 -6). As M2 macrophage polarization is dependent upon IL-4 stimulation, this cytokine and its signaling pathways represent excellent targets for asthma therapies.Our previous work has identified IL-4 signaling through the type I IL-4 receptor complex and activation of insulin receptor substrate 2 (IRS-2) 2 as important for the degree of polarization of M2 macrophages (7). IL-4 binds first to the IL-4R␣ chain with high affinity followed by recruitment of the common ␥ chain (IL-2R␥ or ␥C) to create a functional type I receptor. Assembly of this receptor complex leads to recruitment and phosphorylation of the JAK1 and -3 proteins followed by robust, yet transient, tyrosine phosphorylation of IRS-2 and STAT6. Phosphorylated STAT6 homodimerizes and translocates to the nucleus, ...

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A multi‐centre study of candidate genes for wheeze and allergy: the International Study of Asthma and Allergies in Childhood Phase 2

Cited by 55 publications

References 29 publications

Scientific Opinion on the evaluation of allergenic foods and food ingredients for labelling purposes

Scientific Opinion on the evaluation of allergenic foods and food ingredients for labelling purposes

IL-23, rather than IL-17, is crucial for the development of ovalbumin-induced allergic rhinitis

The TORC1-activated Proteins, p70S6K and GRB10, Regulate IL-4 Signaling and M2 Macrophage Polarization by Modulating Phosphorylation of Insulin Receptor Substrate-2

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