SciCombinator

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Concept: Allergy

173

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a specific form of wheat allergy typically induced by exercise after ingestion of wheat products. Wheat ω-5 gliadin is a major allergen associated with conventional WDEIA, and detection of serum immunoglobulin E (IgE) specific to recombinant ω-5 gliadin is a reliable method for its diagnosis. Recently, an increased incidence of a new subtype of WDEIA, which is likely to be sensitized via a percutaneous and/or rhinoconjunctival route to hydrolyzed wheat protein (HWP), has been observed. All of the patients with this new subtype had used the same brand of soap, which contained HWP. Approximately half of these patients developed contact allergy several months later and subsequently developed WDEIA. In each of these patients, contact allergy with soap exposure preceded food ingestion-induced reactions. Other patients directly developed generalized symptoms upon ingestion of wheat products. The predominant observed symptom of the new WDEIA subtype was angioedema of the eyelids; a number of patients developed anaphylaxis. This new subtype of WDEIA has little serum ω-5 gliadin-specific serum IgE.

Concepts: Immune system, Asthma, Hypersensitivity, Immunoglobulin E, Allergy, Mast cell, Wheat, Allergology

172

Resveratrol is a bioactive polyphenol enriched in red wine that exhibits many beneficial health effects via multiple mechanisms. However, it is unclear whether resveratrol is beneficial for the prevention of food allergy. This study investigated whether resveratrol inhibited the development of food allergy by using a mouse model of the disease.

Concepts: Human, Nutrition, Allergy, Mouse, Resveratrol, Wine, Polyphenol, French Paradox

171

Recent studies have shown that zinc ion (Zn) can behave as an intracellular signaling molecule. We previously demonstrated that mast cells stimulated through the high-affinity IgE receptor (FcεRI) rapidly release intracellular Zn from the endoplasmic reticulum (ER), and we named this phenomenon the “Zn wave”. However, the molecules responsible for releasing Zn and the roles of the Zn wave were elusive. Here we identified the pore-forming α(1) subunit of the Cav1.3 (α(1D)) L-type calcium channel (LTCC) as the gatekeeper for the Zn wave. LTCC antagonists inhibited the Zn wave, and an agonist was sufficient to induce it. Notably, α(1D) was mainly localized to the ER rather than the plasma membrane in mast cells, and the Zn wave was impaired by α(1D) knockdown. We further found that the LTCC-mediated Zn wave positively controlled cytokine gene induction by enhancing the DNA-binding activity of NF-κB. Consistent with this finding, LTCC antagonists inhibited the cytokine-mediated delayed-type allergic reaction in mice without affecting the immediate-type allergic reaction. These findings indicated that the LTCC α(1D) subunit located on the ER membrane has a novel function as a gatekeeper for the Zn wave, which is involved in regulating NF-κB signaling and the delayed-type allergic reaction.

Concepts: Immune system, Signal transduction, Asthma, Cell membrane, Cell biology, Immunoglobulin E, Allergy, Mast cell

171

Crosslinking of immunoglobulin E antibodies (IgE) bound at the surface of mast cells and subsequent mediator release is considered the most important trigger for allergic reactions. Therefore, the genetic control of IgE levels is studied in the context of allergic diseases, such as asthma, atopic rhinitis, or atopic dermatitis (AD). We performed genome-wide association studies in 161 Labrador Retrievers with regard to total and allergen-specific immunoglobulin E (IgE) levels. We identified a genome-wide significant association on CFA 5 with the antigen-specific IgE responsiveness to Acarus siro. We detected a second genome-wide significant association with respect to the antigen-specific IgE responsiveness to Tyrophagus putrescentiae at a different locus on chromosome 5. A. siro and T. putrescentiae both belong to the family Acaridae and represent so-called storage or forage mites. These forage mites are discussed as major allergen sources in canine AD. No obvious candidate gene for the regulation of IgE levels is located under the two association signals. Therefore our studies offer a chance of identifying a novel mechanism controlling the host’s IgE response.

Concepts: Immune system, White blood cell, Asthma, Hypersensitivity, Immunoglobulin E, Allergy, Mast cell, Atopy

170

BACKGROUND: Food allergy has been reported increasingly around the world during the past several decades. Epstein-Barr virus (EBV), a common herpesvirus with high infection rate, is now suspected to be a risk or protective factor in food allergy. The aim of the study was to investigate the possible role of EBV infection in IgE-mediated food allergy. METHODS: 34 patients with an egg allergy and 34 healthy controls participated in this study. Egg allergy was confirmed by open-food challenge. Serum anti-viral capsid antigen (VCA), anti-Epstein-Barr nuclear antigen 1 (EBNA-1) IgG and egg specific (yolk and white)-IgE levels were evaluated by enzyme linked immunosorbent assay (ELISA). At the same time, EBV DNA as well as viral miRNAs in these samples was quantified by real-time PCR. RESULTS: The results showed that serum anti EBNA-1 IgG and two viral miRNAs (miR-BART1-5p and miR-BART7) were highly expressed in patients with egg allergy compared with healthy controls (p < 0.05, < 0.001 and < 0.01, respectively). Moreover, the expressions of anti EBNA-1 specific IgG, miR-BART1-5p and miR-BART7 positively correlated with the level of egg-specific IgE (p < 0.05, < 0.01 and < 0.01, respectively). The differences in anti VCA IgG concentration and EBV DNA copy number between the allergy patients and control individuals were not statistically significant. CONCLUSIONS: The high expression of EBV-specific antibody and miRNAs indicated that EBV infection might play a promoting role in IgE-mediated egg food allergy, and viral miRNAs-related immunomodulatory pathway was likely involved in this allergy process.

Concepts: Immune system, Antibody, Virus, Egg, Immunology, Allergy, Food allergy, Epstein-Barr virus

170

Food allergy has increased dramatically in prevalence over the past decade in westernized countries, and is now a major public health problem. Unfortunately for patients with food allergy, there is no effective therapy beyond food allergen avoidance, and rapid medical treatment for accidental exposures. Recently, oral immunotherapy (OIT) has been investigated as a treatment for this problem. In this review, we will discuss the progress in developing OIT for food allergy, including a novel approach utilizing Xolair (anti-IgE monoclonal antibody, omalizumab) in combination with OIT. This combination may enhance both the safety and efficacy of oral immunotherapy, and could lead to a widely available and safe therapy for food allergy.

Concepts: Immune system, Medicine, Asthma, Monoclonal antibodies, Immunology, Immunoglobulin E, Allergy, Food allergy

170

Mast cell-derived mediators mediate several of the pathological features of asthma. Microbial infections induce asthma exacerbations in which the contribution of mast cells remains incomprehensible.

Concepts: Immune system, Bacteria, Asthma, Cell biology, Immunoglobulin E, Allergy, Mast cell, Leukotriene

169

BACKGROUND: Bronchial asthma is one of the most prevalent diseases in Arab children. Environmental pollution has been suggested to be considered causative of asthma, nasal symptoms and bronchitis in both children and adult. The objectives of this study were to evaluate the association between serum polycyclic aromatic hydrocarbons (PAHs) levels, asthma and allergic outcomes among Saudi children aged up to 15 yrs. We hypothesized that increased serum PAHs are associated with allergy, asthma, or respiratory symptoms. METHODS: A total of 195 Saudi children (98 asthma pediatric patients and 97 healthy controls) were randomly selected from the Riyadh Cohort Study for inclusion. The diagnosis of Asthma was based on established pediatric diagnosis and medications taken. RESULTS: Asthma related markers showed highly significant differences between children with and without asthma. Thus IgE, resistin and IL-4 were significantly increased (p 0.004, 0.001 and 0.003, respectively) in children with asthma compared with non-asthma control subjects. GMCSF, IFN-gamma, IL-5, IL-8 and IL-10, on the other hand, were significantly decreased in children with asthma (p 0.003, 0.03, 0.001, 0.004 and 0.03, respectively). Strong associations between serum PAHs levels and biomarkers of childhood asthma were detected in Arabic children. Data confirmed the role of naphthalene, 4H-cyclobenta[def]phenanthrene, 1,2-benzanthracene, chrysene and benzo(e)acephenanthrylene in childhood asthma; levels of these PAHs were correlated with asthma related biomarkers including IgE, resistin, GMCSF and IFN-gamma as well as IL-4, IL-5, IL-8 and IL-10 cytokines. CONCLUSIONS: This data highlight the pivotal role of specific PAHs in childhood asthma.

Concepts: Asthma, Allergy, Polycyclic aromatic hydrocarbon, Benzene, Hydrocarbon, Aromaticity, Naphthalene, Chrysene

169

Airway hyperresponsiveness (AHR) and airway inflammation are key pathophysiological features of asthma. Bronchial provocation tests (BPTs) are objective tests for AHR that are clinically useful to aid in the diagnosis of asthma in both adults and children. BPTs can be either “direct” or “indirect,” referring to the mechanism by which a stimulus mediates bronchoconstriction. Direct BPTs refer to the administration of pharmacological agonist (e.g., methacholine or histamine) that act on specific receptors on the airway smooth muscle. Airway inflammation and/or airway remodeling may be key determinants of the response to direct stimuli. Indirect BPTs are those in which the stimulus causes the release of mediators of bronchoconstriction from inflammatory cells (e.g., exercise, allergen, mannitol). Airway sensitivity to indirect stimuli is dependent upon the presence of inflammation (e.g., mast cells, eosinophils), which responds to treatment with inhaled corticosteroids (ICS). Thus, there is a stronger relationship between indices of steroid-sensitive inflammation (e.g., sputum eosinophils, fraction of exhaled nitric oxide) and airway sensitivity to indirect compared to direct stimuli. Regular treatment with ICS does not result in the complete inhibition of responsiveness to direct stimuli. AHR to indirect stimuli identifies individuals that are highly likely to have a clinical improvement with ICS therapy in association with an inhibition of airway sensitivity following weeks to months of treatment with ICS. To comprehend the clinical utility of direct or indirect stimuli in either diagnosis of asthma or monitoring of therapeutic intervention requires an understanding of the underlying pathophysiology of AHR and mechanisms of action of both stimuli.

Concepts: Immune system, Inflammation, Asthma, Allergy, Mast cell, Histamine, Nitric oxide, Exhaled nitric oxide

168

Viral infection during pregnancy has been correlated with increased frequency of autism spectrum disorder (ASD) in offspring. This observation has been modeled in rodents subjected to maternal immune activation (MIA). The immune cell populations critical in the MIA model have not been identified. Using both genetic mutants and blocking antibodies in mice, we show that retinoic acid receptor-related orphan nuclear receptor γt (RORγt)-dependent effector T lymphocytes [e.g., T helper 17 (TH17) cells] and the effector cytokine interleukin-17a (IL-17a) are required in mothers for MIA-induced behavioral abnormalities in offspring. We find that MIA induces an abnormal cortical phenotype, which is also dependent on maternal IL-17a, in the fetal brain. Our data suggest that therapeutic targeting of TH17 cells in susceptible pregnant mothers may reduce the likelihood of bearing children with inflammation-induced ASD-like phenotypes.

Concepts: Immune system, White blood cell, Antibody, Protein, Gene, Bacteria, B cell, Allergy