Development Of Respiratory Allergy Research Articles

Birch pollen-The unpleasant herald of spring.

Type I respiratory allergies to birch pollen and pollen from related trees of the order Fagales are increasing in industrialized countries, especially in the temperate zone of the Northern hemisphere, but the reasons for this increase are still debated and seem to be multifaceted. While the most important allergenic molecules of birch pollen have been identified and characterized, the contribution of other pollen components, such as lipids, non-allergenic immunomodulatory proteins, or the pollen microbiome, to the development of allergic reactions are sparsely known. Furthermore, what also needs to be considered is that pollen is exposed to external influences which can alter its allergenicity. These external influences include environmental factors such as gaseous pollutants like ozone or nitrogen oxides or particulate air pollutants, but also meteorological events like changes in temperature, humidity, or precipitation. In this review, we look at the birch pollen from different angles and summarize current knowledge on internal and external influences that have an impact on the allergenicity of birch pollen and its interactions with the epithelial barrier. We focus on epithelial cells since these cells are the first line of defense in respiratory disease and are increasingly considered to be a regulatory tissue for the protection against the development of respiratory allergies.

Avoidance measures for mite allergy—an update

AbstractHouse dust mites are a major source of allergens in house dust and, thus, the main trigger of perennial allergic respiratory diseases [1–5]. Scientific research on the life cycle, diet, and reproductive behavior of dust mites and on the biology of mite allergens has uncovered mechanisms leading to the development of respiratory allergies and suggests measures that can minimize exposure to dust mite allergens. Here, we discuss the evidence linking house dust mite exposure and respiratory allergies and present the efficacy of avoidance measures and their scientific evidence.

Atopic dermatitis: clinical phenotypes, persistence and comorbidity

Background. Atopic dermatitis is the most common skin disease among children. Its natural history is heterogeneous with a difference in age of manifestation, localization of lesions, severity, sensitization profiles, presence of comorbid atopic conditions, and longitudinal trajectories of disease progression. The study aimed to assess the impact of factors such as the onset of the disease, atopic family history, presence of concomitant allergic pathology, duration of breastfeeding on the course of the disease and the development of respiratory allergies, and the impact of environmental factors that aggravate the disease. Materials and methods. Children with atopic dermatitis (n = 88) were included in the study from September 2020 to April 2021 in Kyiv, Ukraine. Symptoms of respiratory allergy in the history of patients have been documented as comorbidity. Results. Total of 88 patients at the time of examination presented with manifestations of atopic dermatitis in the form of a rash, dry skin, scaling, itching, lichenization. The disease severity was significantly related to the age of onset: children with early phenotype had more severe disease (OR = 16.261; 2.056–127.911). There was no statistically significant association of early phenotype of atopic dermatitis with the development of concomitant allergic diseases (OR = 1.813; 0.415–7.916). A severe course was observed in the group of children with atopic family history (OR = 2.750; 1.123–6.735). Children with severe atopic dermatitis had a high risk of concomitant respiratory allergy (OR = 5.604; 1.863–16.863). The duration of breastfeeding did not impact the severity of atopic dermatitis (OR = 0.778; 0.119–5.100) and the risk of concomitant atopic diseases (OR = 1.417; 0.444–4.521). The course of atopic dermatitis was influenced by seasonality in 76 children (86.4 %): the condition of the skin deteriorated in the winter. Contact with the animal was associated with exacerbation of atopic dermatitis in 4 (4.5 %) children, food ingestion — in 20 children (25 %), pollen trees and grasses caused exacerbation in 5 children (5.7 %). Conclusions. Children with a severe phenotype of atopic dermatitis are at risk of developing respiratory allergies. Patients with atopic dermatitis who develop symptoms at the age of under 2 years, as well as those with an atopic family history, are at high risk of developing a severe disease phenotype.

Respiratory allergy control by probiotic fermented milk intake: a mouse model from weaning to maturity.

This study is based on our previous research showing that commercial probiotic fermented milk (PFM) intake mitigates respiratory allergy development to ovalbumin (OVA) in adult mice (6-weeks old) increasing specific immunoglobulin (Ig)G2a and interferon (IFN)-γ rather than IgE. The aim was to determine if PFM exerts a protective effect when an allergy model is induced 5 days after weaning and whether the mechanisms involved are similar to those previously reported. Before inducing allergy, a group of 21-day old BALB/c mice received PFM for 10 days to analyse the impact on intestinal epithelial cells (IECs) activation. Two more groups received PFM for 5 days and were sensitised with OVA; only one group continued taking PFM until the end of the experiment. Sensitisation scheme: 3 OVA injections 1% in phosphate buffered saline (PBS) plus 7 days OVA aerosol exposure and re-stimulus 15 days later. The contents of specific- IgE, IgG, total-secretory-IgA and Th1/Th2 balance in serum, bronchoalveolar lavage (BAL) and gut were measured at 7 and 15 days post-sensitisation (dPS) and 2 days post-re-stimulus (2dPR). Treg cells in lungs were also quantified. Results were compared with normal and sensitised controls. PFM induced mild activation of IECs increasing monocyte chemoattractant protein-1 (MCP-1 or CCL2) and interleukin (IL)-6 production. In sensitised mice, PFM controlled the response inducing IgG rather than IgE at 7 and 15-dPS and 2dPR (60 days old). Th1-balance (IFN-γ) was favoured by PFM in lungs at 7 dPS with low levels of IL-10 released to regulate the response. Total-S-IgA increased in lungs and gut; however, PFM intake did not affect Treg cells in lungs. PFM maintains controlled stimulation of the immune cells involved in Th1 response, favouring IgG at the respiratory mucosal site. Although the effect was not as strong as that reported previously, PFM promoted maturation and activation of gut immune cells preserving intestinal homeostasis and lung immune response.

Acute and Subacute Oral Toxicity of Deoxynivalenol Exposure in a Dermatophagoides farinae-Induced Murine Asthma Model.

Previously, researchers have demonstrated that mycotoxin deoxynivalenol (DON) significantly enhances immunocyte activation. However, the interaction between DON exposure and immune disorders remains unclear. In this study, we aimed to investigate whether acute and subacute oral exposure to DON exacerbates the development of respiratory allergy using a mite allergen (Dermatophagoides farina, Derf)-induced mouse model of asthma. The direct relationship between DON exposure and asthma development was examined following acute oral DON administration (0, 0.1, or 0.3 mg/kg body weight), immediately before the final mite allergen challenge. Simultaneously, the influence of subacute oral exposure via low dose DON contaminated wheat (0.33 ppm) was evaluated using the same settings. To detect the proinflammatory effects of DON exposure, we examined the total and Derf-specific serum IgE levels, histology, number of immunocytes, and cytokine and chemokine secretion. Acute oral DON significantly enhanced the inflammatory responses, including cellular infiltration into bronchoalveolar lavage fluid, infiltration of immunocytes and cytokine production in local lymph nodes, and cytokine levels in lung tissues. Corresponding proinflammatory responses were observed in a mouse group exposed to subacute oral DON. In vivo results were validated by in vitro experiments using the human bronchial epithelial (BEAS-2B) and human eosinophilic leukemia (EOL-1) cell lines. Following exposure to DON, the secretion of interleukin (IL)-1β, IL-6, IL-8, and/or tumor necrosis factor-α in BEAS-2B cells, as well as EoL-1 cells, increased significantly. Our findings indicate that DON exposure is significantly involved in the proinflammatory response observed in respiratory allergy.

TNF-α (rs1800629) polymorphism modifies the effect of sensitization to house dust mite on asthma and bronchial hyperresponsiveness in children

Asthma is a complex disease, with various genetic and environmental factors implicated in its development. Sensitization to the house dust mite (HDM) is closely linked with the development of respiratory allergies, including asthma. However, some children sensitized to HDM do not complain of any symptoms of respiratory allergies, even though HDM is correlated with an increased risk for developing asthma, suggesting the involvement of other factors. Tumor necrosis factor (TNF)-α is associated with the pathophysiologies of asthma in combination with its genetic polymorphism. The aim of the present study was to elucidate the associations between sensitization to HDM, polymorphism of TNF-α rs1800629, and asthma/bronchial hyperresponsiveness (BHR). Our results revealed that sensitization to HDM is associated with asthma diagnosis in lifetime, current asthma, and BHR in Korean children. Furthermore, the genetic polymorphism of TNF-a rs1800629 was found to modify and interact with these associations. This study suggests that prevention strategies for childhood asthma need to be targeted according to genetic susceptibility.

Association of pulmonary, cardiovascular, and hematologic metrics with carbon nanotube and nanofiber exposure among U.S. workers: a cross-sectional study

BackgroundCommercial use of carbon nanotubes and nanofibers (CNT/F) in composites and electronics is increasing; however, little is known about health effects among workers. We conducted a cross-sectional study among 108 workers at 12 U.S. CNT/F facilities. We evaluated chest symptoms or respiratory allergies since starting work with CNT/F, lung function, resting blood pressure (BP), resting heart rate (RHR), and complete blood count (CBC) components.MethodsWe conducted multi-day, full-shift sampling to measure background-corrected elemental carbon (EC) and CNT/F structure count concentrations, and collected induced sputum to measure CNT/F in the respiratory tract. We measured (nonspecific) fine and ultrafine particulate matter mass and count concentrations. Concurrently, we conducted physical examinations, BP measurement, and spirometry, and collected whole blood. We evaluated associations between exposures and health measures, adjusting for confounders related to lifestyle and other occupational exposures.ResultsCNT/F air concentrations were generally low, while 18% of participants had evidence of CNT/F in sputum. Respiratory allergy development was positively associated with inhalable EC (p=0.040) and number of years worked with CNT/F (p=0.008). No exposures were associated with spirometry-based metrics or pulmonary symptoms, nor were CNT/F-specific metrics related to BP or most CBC components. Systolic BP was positively associated with fine particulate matter (p-values: 0.015-0.054). RHR was positively associated with EC, at both the respirable (p=0.0074) and inhalable (p=0.0026) size fractions. Hematocrit was positively associated with the log of CNT/F structure counts (p=0.043).ConclusionsMost health measures were not associated with CNT/F. The positive associations between CNT/F exposure and respiratory allergies, RHR, and hematocrit counts may not be causal and require examination in other studies.

Airway IL-1α promotes development of allergen-specific follicular helper T (Tfh) cells and production of IgE antibody

Recent literature suggests that Tfh cells that produce IL-4 play a pivotal role in allergic immune responses. However, the molecular and immunological mechanisms involved in the development of Tfh cells are not fully understood. The goal of this study was to test the hypothesis that IL-1α released from alveolar macrophage plays a pivotal role in respiratory allergy. Naïve wild-type BALB/c mice and IL-4 reporter 4get mice were exposed intranasally (i.n.) to a model antigen ovalbumin (OVA) with or without serial dilutions of IL-1α. Development of allergic immune responses was analyzed by collecting mediastinal lymph nodes (mLNs) and sera, and by challenging the animals i.n. with OVA antigen. Alveolar macrophages were isolated of naïve BALB/c mice and stimulated in vitro with pollens of short ragweed or Japanese cedar. The mice exposed i.n. to OVA with IL-1α produced OVA-specific IgE antibody; the IgE response was dependent on the doses of IL-1α. These mice showed airway eosinophilia and increased lung levels of type 2 cytokines when challenged i.n. with OVA. Marked increase in the IL-4eGFP+CD4+CXCR5+ST2- Tfh cell population was observed in mLNs of mice exposed OVA plus IL-1α as compared to those mice exposed to OVA alone. Furthermore, alveolar macrophages produced and released IL-1α extracellular when they were exposed to allergen pollens in vitro. IL-1α produced by alveolar macrophages by airway allergen exposure may paly a pivotal role to promote generation of antigen-specific Tfh cells and hence development of respiratory allergy.

Respiratory sensitization: toxicological point of view on the available assays.

Respiratory sensitization as a consequence of exposure to chemical products has increased over the last decades, leading to an increase of morbidity. The increased use of synthetic compounds resulted in an exponential growth of substances to which we are potentially exposed on a daily basis. Some of them are known to induce respiratory sensitization, meaning that they can trigger the development of allergies. In the past, animal studies provided useful results for the understanding of mechanisms involved in the development of respiratory allergies. However, the mechanistic understanding of the involved cellular effects is still limited. Currently, no in vitro or in vivo models are validated to identify chemical respiratory sensitizers. Nonetheless, chemical respiratory sensitizers elicit a positive response in validated assays for skin sensitization. In this review, we will discuss how these assays could be used for respiratory sensitization and if necessary, what can be learnt from these assays to develop a model to assess the respiratory sensitizing potential of chemicals. In the last decades, much work has been done to study the respiratory toxicity of inhaled compounds especially in developing in vitro assays grown at the air-liquid interface. We will discuss how possibly the tests currently used to investigate general particle toxicity could be transformed to investigate respiratory sensitization. In the present review, we describe the most known mechanism involved in the sensitization process and the experimental in vivo and alternative in vitro models, which are currently available and how to adapt and improve existing models to study respiratory sensitization.

Development of Respiratory Allergies, Asthma and Allergic Rhinits in Children with Atopic Dermatitis.

Children with atopic dermatitis (AD) usually develop symptoms when they reach the age of 6-7 years, but the risk of developing respiratory allergies, asthma and allergic rhinitis (AR) remains high. In most children with AD, the development of asthma and AR is associated with sensitization to food allergens and/or aeroallergens, while only a small percentage missed atopic diathesis. In about 35% of children with AD, food allergy is the provoking cause, and 60% of infants who had AD in the first 3 months of life were sensitized against aeroallergens by the age of 5. The aim of the study was to follow development of asthma and AR and to assess the most significant risk factors for developing respiratory allergy. A total of 114 children with AD were followed up for five years. At annual visits, the severity of disease, total immunoglobulin E (IgE) antibody values, skin prick tests, specific IgE antibodies to food allergens and aeroallergens, and absolute eosinophil count were assessed. Information on the family history of atopy and AD, feeding patterns during infancy, data on sensitivity to food allergens and/or aeroallergens, and on the occurrence of bronchial obstruction and nose symptoms were obtained. Asthma developed in 36 children, median age 7.7 years; 33 children had symptoms of AR, and 13 children with AD had both diseases associated; 38 children had sensitivity to food, of which 24 developed asthma and 13 AR; asthma developed in 18/23 children with sensitivity to aeroallergens, and almost an equal number of children developed AR. The increased absolute eosinophil count and specific IgE to aeroallergens and food allergens were the best asthma predictors, while AR predictors were family history and early onset of AD. In conclusion, children with AD are at a significant risk of developing respiratory allergies, and those with the increased absolute eosinophil count, positive specific IgE to aeroallergens and food allergens, heredity of AD, and early onset of AD are at the highest risk. Identification of risk factors will enable us to improve the treatments of AD in order to reduce the severity of disease and prevent manifestation of respiratory allergy.

IgE-hypersensitivity to allergens of the fungi Rhizopus Nigricans and Cladosporium Herbarum in childrenwith respiratory allergies

A survey of 111 children diagnosed with respiratory allergies (allergic rhinitis, allergic bronchitis, obstructive bronchitis, recurrent bronchitis, bronchial asthma) aged 1 year to 17 years, of which 58 children have a diagnosis of atopic bronchial asthma of different severity. All children are at risk for the development of fungal sensitization, having a household contact with these allergens. Allergological diagnostics was performed by ELISA using a panel of pediatric and fungal (Rhizopus nigricans and Cladosporium herbarum) biotinylated allergens. As a result of the study revealed that allergens mold Rhizopus nigricans and Cladosporium herbarum are the causal significant factor in the development of respiratory allergies, including asthma, in children at risk. Most often a high level of hypersensivity to Rhizopus nigricans is seen in children aged 2-5 years, Cladosporium herbarum - aged 6-9 years, concomitant to both fungal allergens at the age of 10-17 years. The correlation between the severity of atopic process and degree of sensitization to fungal allergens was not detected. All children with atopic asthma have polyvalent sensitization. Allergens mold Rhizopus nigricans and Cladosporium herbarum must be taken into account in the preparation of a diagnostic panel for children with respiratory allergies at risk. It is necessary to support drug therapy of respiratory allergy in children the activities aimed at elimination of cause significant fungal sensitization everyday surroundings.

The epidemiologic characteristics of healthcare provider-diagnosed eczema, asthma, allergic rhinitis, and food allergy in children: a retrospective cohort study.

BackgroundThe rates of childhood allergic conditions are changing, prompting the need for continued surveillance. Examination of healthcare provider-based diagnosis data is an important and lacking methodology needed to complement existing studies that rely on participant reporting.MethodsUtilizing our care network of 1,050,061 urban and sub-urban children, we defined two retrospective cohorts: (1) a closed birth cohort of 29,662 children and (2) a cross-sectional cohort of 333,200 children. These cohorts were utilized to determine the epidemiologic characteristics of the conditions studied. Logistic regression was utilized to determine the extent to which food allergy was associated with respiratory allergy.ResultsIn our birth cohort, the peak age at diagnosis of eczema, asthma, rhinitis, and food allergy was between 0 and 5 months (7.3 %), 12 and 17 months (8.7 %), 24 and 29 months (2.5 %), and 12 and 17 months (1.9 %), respectively. In our cross-sectional cohort, eczema and rhinitis prevalence rates were 6.7 % and 19.9 %, respectively. Asthma prevalence was 21.8 %, a rate higher than previously reported. Food allergy prevalence was 6.7 %, with the most common allergenic foods being peanut (2.6 %), milk (2.2 %), egg (1.8 %), shellfish (1.5 %), and soy (0.7 %). Food allergy was associated with development of asthma (OR 2.16, 95 % CI 1.94-2.40), and rhinitis (OR 2.72, 95 % CI 2.45-3.03).ConclusionsCompared with previous reports, we measure lower rates of eczema and higher rates of asthma. The distribution of the major allergenic foods diverged from prior figures, and food allergy was associated with the development of respiratory allergy. The utilization of provider-based diagnosis data contributes an important and lacking methodology that complements existing studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12887-016-0673-z) contains supplementary material, which is available to authorized users.

A child’s spit epigenome can reveal its respiratory allergy risk

Environmental exposures like parental lifestyle and diet, smoking, obesity and exposure to toxin can modulate disease risk. Epigenetic DNA methylation changes can be part of the underlying molecular mechanisms. Early life exposures can alter DNA methylation patterns, and thereby predispose the child to develop respiratory allergy (RA) later in life. Longitudinal birth cohorts are instrumental to study disease development, but DNA biomarker research is hampered because blood sampling is kept to a minimum for practical and ethical reasons. Saliva is a non-invasive and convenient source of DNA that can be used for biomarker research. In this study, we aimed at discovery and confirmation of differential methylation regions (DMR) in saliva of children with RA when comparing to controls. Saliva samples collected in two independent longitudinal birth cohorts in Belgium were analyzed using Illumina Methylation 450K BeadChips.A statistical analysis pipeline was developed in R to identify genome-wide differential methylation. The Illumina Methylation 450K BeadChips revealed 13 DMR in saliva from 11y old allergic children (N=26) vs. controls (N=20). 5 DMR were located in genes involved in IL4 signalling and Th2-response, showing a link with wheezing and other RA phenotypes. The 13 DMR were selected for further biological and technical validation by iPLEX MassArray analysis in the same birth cohort as well as in a second cohort (N=78). This project is providing novel insights in the molecular mechanisms that may predispose children to RA development. We are among the first to show the utility of saliva to identify DNA methylation marks in children that are relevant for RA.

Sensitization to workplace respiratory allergens among bakery workers in Douala, Cameroon: a cross-sectional study.

BackgroundSensitization to flour or fungal alpha-amylase is a prerequisite for the development of respiratory allergy in bakers. The knowledge of occupational allergen sensitization among bakery workers will facilitate the implementation of preventive measures for respiratory allergies in bakeries. The objective of this study was to determine the prevalence and factors associated with sensitization to wheat flour and α-amylase in bakers in Douala.MethodsA cross-sectional study was conducted in 42 of the 151 bakeries that are present in the city of Douala. Demographics, clinical data, as well as results of skin prick tests to wheat flour, α-amylase and common aeroallergens were collected from all participants. A logistic regression model of the SPSS.20 software was used to identify factors associated with sensitization to wheat flour and α-amylase.ResultsOf the 229 participants included in the study, 222 (96.9%) were male. The mean age was 36.3 ± 8.9 years. The prevalence of sensitization to flour and α-amylase were 16.6% and 8.3% respectively. After multivariate analysis, factors associated with sensitization to flour were work seniority and sensitization to storage mites while an age of 30 years and above was the only factor associated with sensitization to α-amylase.ConclusionBakers in Douala are at risk of sensitization to occupational allergens. The environmental hygiene in bakeries, health surveillance and the use of personal protective equipment could reduce the risk of respiratory allergies among bakers.

Consecutive food and respiratory allergies amplify systemic and gut but not lung outcomes in mouse

Aims Increasing clinical data suggest a link between food allergy and the later development of respiratory allergy. This progression may be triggered by exposures to different allergens but the mechanism implicated remains unknown. This study aimed to identify the impact of a first exposure to food allergen on the development of a new form of allergy caused by exposure to a novel allergen using a mouse model. Method In our model, mice were intraperitoneally sensitized to wheat proteins (modified gliadins) to induce a systemic response, then they were exposed orally to the same allergen and finally they were intranasally exposed to HDM (Dermatophagoides farinae extract) a respiratory allergen without adjuvant to assess an impact on lung mucosa. Results After food and respiratory allergen exposures, mice displayed stronger amount of blood markers: IgE specific and histamine. Moreover, splenocyte secretion of IL-4 and IL-17 were increased whereas weaker levels of IFNg were observed. In parallel, Peyer patches lymphocytes secreted higher amount of IL-4 with a decreased in IFNg, IL-10 and TGF-b productions. These mice exhibited intestine damages, higher paracellular flux and modification of transcellular permeability. In contrast, airway hyperresponsiveness, inflammatory cells and cytokines in lung remained unchanged compared to the respiratory allergy model. Conclusion We show that dual exposure induces a raise in specific IgE and local Th2 and Th17 cytokines secretion before triggering phase. During the latter, gut morphology and functions were affected but not lung in dual exposed mice compared to single one underlying the organospecific impact. Altogether, our data make a step further in the elucidation of the mechanisms linking allergy history to immunological and clinical status potentially linked to atopic march development.

Perinatal stress and food allergy: a preliminary study on maternal reports

Maternal stress in fetal and early life has been associated with the development of respiratory allergies, but no studies exist about food allergy. Stressful events and the quality of caregiving provided, as they affect the emotional and physiologic regulation of the infant, could alter the hypothalamic–pituitary–adrenal and immune system, facilitating an increased allergic response. This study aimed to investigate the influence of perinatal stress, as perceived by mothers, on developing food allergy in childhood. A survey on pregnancy and the first three months after giving birth was submitted to 59 Italian mothers of at least one child suffering from severe food allergy and one completely healthy child, for a total of 118 children examined. The presence of stressful events and the quality of perinatal period for each child were assessed retrospectively. The food allergic children’s data were compared to siblings’ data through inferential statistics. The results showed a significantly higher number of stressful events occurred during patients’ perinatal period, compared to siblings, in particular bereavements in pregnancy and parenting difficulties in postpartum. Mothers reported harder pregnancies and more stressful, harder, and, in general, worse postpartum when referring to their food-allergic children, in comparison with their siblings (p < .05). Psychological aspects are demonstrated to be involved in the development of allergic diseases. This study constitutes the first step to examine the role of early stress and perinatal psychosocial factors in the pathogenesis of food allergy; further studies are necessary to understand individual psychological impact and its relations with genetic and biological factors.

Pilot Study to Compare DNA Methylation Patterns in Blood and Saliva in Respiratory Allergy Cases and Healthy Controls

There is convincing evidence that environmental and lifestyle factors contribute to the development of respiratory allergies (RA), especially if these exposures occur during fetal and early-life development. The underlying mechanisms are still undiscovered, but changes in the epigenetic regulation of gene expression (such as DNA methylation) is plausible. Longitudinal (birth) cohorts are instrumental to study the epigenetic relation between early-life environmental factors and the development of RA, but investigations are hampered since blood sampling in children is kept minimal for practical and ethical reasons. Saliva is suggested as an alternative DNA source because the samples can be obtained in a decentralized manner with less constraints. It is of interest to know how saliva DNA methylation patterns compare with the blood patterns, with the latter being considered as a reflection of systemic effects. The aim of the pilot study was to set up an analysis pipeline for whole-genome DNA methylation analysis using the Illumina BeadChip platform and to investigate the comparability of DNA methylation patterns in mononuclear cells (MNC) versus saliva samples. Furthermore, we hypothesized that differential DNA methylation can be detected in respiratory allergy (RA) cases (n=5) when compared to healthy controls (n=5). The methylation status of the majority of the probes was comparable between MNC and saliva with about 10% of the probes having a differential methylation pattern (p&lt;0.05 and ß-value&gt;10%). When cases were compared with healthy controls, 216 differentially methylated probes were identified in common between MNC and saliva samples. All the probes showed the same methylation polarity. Some probes were linked to RA, but bioinformatics analysis did not identify enriched pathways. We selected a list of 12 differentially methylated regions for further biological and technical validation with bisulfite pyrosequencing and those results will be presented.

14: Previous food allergy aggravates allergic markers and intestinal damages in a mouse model of asthma

Aims Increasing clinical data suggest a link between food allergy and the later development of respiratory allergy. This progression may be triggered by exposures to different allergens but the mechanism implicated remains unknown. This study aimed to identify the impact of a first exposure to food allergen on the development of a new form of allergy caused by exposure to a novel allergen using a mouse model. Method In our model, mice were intraperitoneally sensitized to wheat proteins (modified gliadins) to induce a systemic response, then they were exposed orally to the same allergen and finally they were intranasally exposed to HDM (Dermatophagoides farinae extract) a respiratory allergen without adjuvant to assess an impact on lung mucosa. Results After food and respiratory allergen exposures, mice displayed stronger amount of blood markers: IgE specific and histamine. Moreover, splenocyte secretion of IL-4 and IL-17 were increased whereas weaker levels of IFN γ were observed In parallel Peyer patches lymphocytes secreted higher amount of IL-4 with a decreased in IFN γ , IL-10 and TGF- β productions. These mice exhibited intestine damages, higher paracellular flux and modification of transcellular permeability. In contrast, airway hyper-responsiveness, inflammatory cells and cytokines in lung remained unchanged compared to the respiratory allergy model. Conclusion We show that dual exposure induces a raise in specific IgE and local Th2 and Th17 cytokines secretion before triggering phase. During the latter, gut morphology and functions were affected but not lung in dual exposed mice compared to single one underlying the organospecific impact. Altogether, our data make a step further in the elucidation of the mechanisms linking allergy history to immunological and clinical status potentially linked to atopic March development.

Association of HLA-G 14bp insertion/deletion and TGF-β1 polymorphisms with atopic asthma monosensitized against Der p 1: An Algerian study with a review of the literature

Abstract Introduction Genetic diversity of HLA-G consists of sequence variations in promoter, exonic and 3′ untranslated (3′UTR) regions. Polymorphisms in the HLA-G promoter region had previously been associated with asthma. Of interest is also the fact that the genes encoding the effectors IL-10 and TGF-β1 (immunosuppressive molecules controlling the immune response in respiratory allergy) also exhibit genetic polymorphisms in populations. Objectives To investigate the potential role of the 14-bp insertion/deletion polymorphism in conjunction with IL-10 and TGF-β1 genes polymorphisms in respiratory allergy development. Methods The study involved 125 patients suffering from atopic asthma, all monosensitized against Der p 1 and 100 matched-controls, all originating from Algeria. PCR-based techniques were used to assess HLA-G, IL-10 and TGF-β1 genotypes. Results While the frequency of IL-10 gene polymorphisms did not differ between patients and controls, 3′UTR +14 bp insertion allele was significantly more frequent in patients group than in control group (P = 0.006) with the homozygous state of the 14-bp deletion allele being more frequent in controls (P = 0.02). TGF-β1 +869T/C polymorphism analysis showed a significant difference between allergic patients and controls for TC genotype (P = 0.03). Discussion Our findings suggest that HLA-G gene may participate in the pathogenesis of asthma in our population. A possible mechanism is that diminished immunosuppressive activity, mediated by HLA-G, may contribute to initiation/persistence of chronic airway inflammation in asthma. On the other hand, TC/GG are less frequent in atopic patients than in controls. This can be explained by the association of this haplotype with a high production of TGF-β1.

340 Sensitization to Aeroallergens and Risk of Respiratory Allergy in Atopic Dermatitis Children

BackgroundInfants and young children with atopic dermatitis (AD) are at grate risk of developing respiratory allergy later in life with rhinitis, eye symptoms, and sometimes asthma. The aim of our study was to describe the sensitization patterns to inhalants in our young patients with AD and to assess the relation between early sensitization to aeroallergens and the development of respiratory allergy.Methods80 children diagnosed of AD, aged from 11 to 34 months, were included (51 male and 29 female). Seventy two of these 80 were followed up to 7 years of age. Except a clinical examination, total IgE level was investigated by ELISA, and analysis of specific IgE antibodies to aeroallergens was performed with MAST CLA Allergen specific IgE Assay. Nonparametric tests were used in comparative analysis.Results79% of our infants with AD had increased level of total IgE (mean: 387 kU/L). Sensitization to inhalant allergens was determined in 52 atopic dermatitis children (65%). The most relevant results were: 39 patients (48.8%) were sensitized to pets, 36 patients (45.0%) were sensitized to house-dust mites, 25 patients (31.3%) were sensitized to pollen, 17 patients (21.5%) were sensitized to molds. During the follow up, 48% of patients developed asthma and 52% allergic rhinitis. The mean age of respiratory allergy onset was 29.8 ± 3.9 months. At the end of our study the cumulative prevalence of respiratory allergy symptoms was significantly higher in children with inhalant sensitization compared to children without sensitization to aeroallergens (71% vs 18%, P < 0.001). The risk of asthma in that group also was significantly higher (68% vs 14%, P < 0.001).ConclusionsEarly sensitization to aeroallergens in AD children is associated with increased risk of development of respiratory allergic symptoms later in life.