Allergic Phenotype Research Articles

Probiotics in obstetric practice: efficacy and safety

The intestinal microbiota modulates immune programming and can prevent the realization of an allergic phenotype. For the formation of a normal microbiocenosis of the intestine, skin and oral cavity, a sufficient quantitative and qualitative bacterial colonization of the newborn is necessary during the transition from a sterile intrauterine environment to microbial colonization, resulting in the appearance of more than 1014 microorganisms. Low levels of bifidobacteria and early colonization of potentially pathogenic bacteria are associated with the development of severe allergic reactions. Prescribing probiotics containing Lactobacillus rhamnosus GG (LGG) at a concentration of 1081010 CFU from 36 weeks of gestation and during the first 34 months of lactation is associated with a 21% reduction in the risk of allergic reactions in the child.

Oral Feeding of Cow Milk Containing A1 Variant of \u03b2 Casein Induces Pulmonary Inflammation in Male Balb/c Mice

Milk is globally consumed as a rich source of protein and calcium. A major protein component of milk is casein, with β-casein having 2 major variants A1 and A2. Of these, A1 casein variant has been implicated as a potential etiological factor in several pathologies, but direct effect on lungs has not been studied. The objective of the present study was to evaluate the A1and A2 β casein variants of cow milk as factors causing allergic airway disease in murine model. Mice fed with A1A1 milk exhibited increased airway hyperresponsiveness with increasing concentration of bronchoconstrictor (methacholine), which was not observed in mice fed with A2A2 milk. Significantly elevated levels of IL-4 and IL-5 were found in bronchoalveolar lavage and serum of A1A1 variant fed mice. Increased IgE and IgG levels along with increased infiltration of lymphocytes and eosinophils, leading to peribronchial inflammation was also observed in A1A1 variant fed mice, although, no goblet cell hyperplasia or airway remodeling was observed. In contrast, A2A2 milk fed mice presented phenotype matching the control group, while A1A2 milk fed group presented an intermediate phenotype. In summary, our results show that A1 form of cow milk has a proinflammatory effect on the lung resulting in phenotype closely matching with the typical allergic asthma phenotype.

Type 2 immunity in the skin and lungs.

There has been extensive progress in understanding the cellular and molecular mechanisms of inflammation and immune regulation in allergic diseases of the skin and lungs during the last few years. Asthma and atopic dermatitis (AD) are typical diseases of type 2 immune responses. interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin are essential cytokines of epithelial cells that are activated by allergens, pollutants, viruses, bacteria, and toxins that derive type 2 responses. Th2 cells and innate lymphoid cells (ILC) produce and secrete type 2 cytokines such as IL-4, IL-5, IL-9, and IL-13. IL-4 and IL-13 activate B cells to class-switch to IgE and also play a role in T-cell and eosinophil migration to allergic inflammatory tissues. IL-13 contributes to maturation, activation, nitric oxide production and differentiation of epithelia, production of mucus as well as smooth muscle contraction, and extracellular matrix generation. IL-4 and IL-13 open tight junction barrier and cause barrier leakiness in the skin and lungs. IL-5 acts on activation, recruitment, and survival of eosinophils. IL-9 contributes to general allergic phenotype by enhancing all of the aspects, such as IgE and eosinophilia. Type 2 ILC contribute to inflammation in AD and asthma by enhancing the activity of Th2 cells, eosinophils, and their cytokines. Currently, five biologics are licensed to suppress type 2 inflammation via IgE, IL-5 and its receptor, and IL-4 receptor alpha. Some patients with severe atopic disease have little evidence of type 2 hyperactivity and do not respond to biologics which target this pathway. Studies in responder and nonresponder patients demonstrate the complexity of these diseases. In addition, primary immune deficiency diseases related to T-cell maturation, regulatory T-cell development, and T-cell signaling, such as Omenn syndrome, severe combined immune deficiencies, immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome, and DOCK8, STAT3, and CARD11 deficiencies, help in our understanding of the importance and redundancy of various type 2 immune components. The present review aims to highlight recent advances in type 2 immunity and discuss the cellular sources, targets, and roles of type 2 mechanisms in asthma and AD.

Domestic Risk Factors for Atopic and non-Atopic Asthma in First Nations Children Living in Saskatchewan, Canada.

Both allergic and non-allergic asthma phenotypes are thought to vary by specific housing and other indoor environmental conditions. This study evaluated risk factors for allergic asthma phenotypes in First Nation children, an understudied Canadian population with recognized increased respiratory morbidity. We conducted a cross-sectional survey with a clinical component to assess the respiratory health of 351 school-age children living on two rural reserve communities. Asthma was defined as parental report of physician diagnosed asthma or a report of wheeze in the past 12 months. Atopy was determined by a ≥ 3-mm wheal response to any of six respiratory allergens upon skin prick testing (SPT). Important domestic and personal characteristics evaluated included damp housing conditions, household heating, respiratory infections and passive smoking exposure. Asthma and atopy prevalence were 17.4% and 17.1%, respectively. Of those with asthma, 21.1% were atopic. We performed multivariate multinomial logistic regression modelling with three outcomes: non-atopic asthma, atopic asthma and no asthma for 280 children who underwent SPT. After adjusting for potential confounders, children with atopic asthma were more likely to be obese and to live in homes with either damage due to dampness (p < 0.05) or signs of mildew/mold (p = 0.06). Both natural gas home heating and a history of respiratory related infections were associated with non-atopic asthma (p < 0.01). Domestic risk factors for asthma appear to vary by atopic status in First Nations children. Determining asthma phenotypes could be useful in environmental management of asthma in this population.

Dibutyl Phthalate Augments Allergen-induced Lung Function Decline and Alters Human Airway Immunology. A Randomized Crossover Study.

Rationale: Phthalates are a group of chemicals used in common commercial products. Epidemiological studies suggest that phthalate exposure is associated with development or worsening of allergic diseases such as asthma. However, effects of dibutyl phthalate (DBP) or other phthalates found in high concentrations in indoor air have never been examined in allergic individuals in a controlled exposure setting.Objectives: To investigate the airway effects in humans caused by inhalation of a known concentration of a single phthalate, DBP.Methods: In a randomized crossover study, 16 allergen-sensitized participants were exposed to control air or DBP for 3 hours in an environmental chamber followed immediately by an allergen inhalation challenge. Bronchoalveolar wash and lavage were obtained 24 hours after exposure. Lung function, early allergic response, airway responsiveness, inflammation, immune mediators, and immune cell phenotypes were assessed after DBP exposure.Measurements and Main Results: DBP exposure increased the early allergic response (21.4% decline in FEV1 area under the curve, P = 0.03). Airway responsiveness was increased by 48.1% after DBP exposure in participants without baseline hyperresponsiveness (P = 0.01). DBP increased the recruitment of BAL total macrophages by 4.6% (P = 0.07), whereas the M2 macrophage phenotype increased by 46.9% (P = 0.04). Airway immune mediator levels were modestly affected by DBP.Conclusions: DBP exposure augmented allergen-induced lung function decline, particularly in those without baseline hyperresponsiveness, and exhibited immunomodulatory effects in the airways of allergic individuals. This is the first controlled human exposure study providing biological evidence for phthalate-induced effects in the airways.Clinical trial registered with www.clinicaltrials.gov (NCT02688478).

Anti-IL-5 Biologicals Targeting Severe Late Onset Eosinophilic Asthma.

Improved knowledge about the pathogenesis of asthma has facilitated the development of novel drugs and provided hope for patients with severe asthma. After the short- and long-term success of omalizumab in severe allergic phenotype, researchers have targeted patients with severe eosinophilic asthma who comprise up to 45% of adult severe asthma. Interleukin (IL)-5 and IL-5 receptor subunit α play crucial roles in the development, maturation, and operation of eosinophils. Currently, patients treated with anti-IL-5 biologicals depleting eosinophils experience the positive efficacy of these drugs, especially with regard to the reduction of exacerbation rate. The aim of this review was to shed light on severe eosinophilic asthma treatment with these new currently available agents selectively targeting IL-5 or its receptor, discussing their usage including pre-treatment concerns, such as selecting the target population and choosing the right agent among them, and subsequent assessment of relevant effect and safety issues.

Replication study of susceptibility variants associated with allergic rhinitis and allergy in Han Chinese

BackgroundAllergic rhinitis (AR) is believed to be a complex genetic disease. The last decade has been marked by the publication of more than 20 genome-wide association studies (GWASs) of AR and associated allergic phenotypes and allergic diseases, which have shown allergic diseases and traits to share a large number of genetic susceptibility loci. The aim of present study was therefore to investigate the highly replicated allergy related genes and variants as candidates for AR in Han Chinese subjects.MethodsA total of 762 AR patients and 760 control subjects were recruited, and a total of 58 susceptible variants previously reported to be associated with allergic traits were choose for replication.ResultsLogistic regression analyses revealed that in the co-dominant-effect model as assessed by the AIC, compared with wild-type carriers, significant AR risk were associated with rs9865818 in LPP (P = 0.029, OR = 1.469 for GG vs. AA); rs6554809 in DNAH5 (P = 0.000, OR = 1.597 for TC vs. CC); rs1438673 in WDR36-CAMK4 loci (P = 0.037, OR = 1.396 for CC vs.TT), rs7775228 in HLA region (P = 0.000, OR = 1.589 for TC vs.TT), rs7203459 in CLEC16A (P = 0.025, OR = 0.731 for TC vs. TT).ConclusionWe replicated Han Chinese AR-specific susceptibility loci in LPP, DNAH5, HLA, CLEC16A and WDR36-CAMK4. Further understanding the molecular mechanisms underlying these associations may provide new insights into the etiology of allergic disease.

CME Exam: Allergic Endotypes and Phenotypes of Asthma

CME Exam: Allergic Endotypes and Phenotypes of Asthma

Allergic Endotypes and Phenotypes of Asthma

Allergic asthma is defined as asthma associated with sensitization to aeroallergens, which leads to asthma symptoms and airway inflammation. Allergic asthma is the most common asthma phenotype. The onset of allergic asthma is most often in childhood and is usually accompanied by other comorbidities including atopic dermatitis and allergic rhinitis. It is often persistent although there is a wide variation in disease severity. It is a TH2-driven process. Biomarkers have been identified to distinguish patients with allergic asthma, particularly serum IgE levels, tests to indicate sensitization to aeroallergens such as specific IgE or skin prick test positivity, blood and sputum eosinophil levels, fraction of exhaled nitric oxide, and periostin. Treatments for allergic asthma include environmental control measures, allergen immunotherapy, and glucocorticoids. Biologics, targeting the TH2 pathway, have been shown to be effective in the treatment of allergic asthma.

Alteration of gut microbiota and microbial products in distinct allergic phenotypes: data from an Asian birth cohort study

Alteration of gut microbiota and microbial products in distinct allergic phenotypes: data from an Asian birth cohort study

Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis

Asthma is one of the most common chronic diseases affecting both children and adults. We report a genome-wide association meta-analysis of 69,189 cases and 702,199 controls from Iceland and UK biobank. We find 88 asthma risk variants at 56 loci, 19 previously unreported, and evaluate their effect on other asthma and allergic phenotypes. Of special interest are two low frequency variants associated with protection against asthma; a missense variant in TNFRSF8 and 3‘ UTR variant in TGFBR1. Functional studies show that the TNFRSF8 variant reduces TNFRSF8 expression both on cell surface and in soluble form, acting as loss of function. eQTL analysis suggests that the TGFBR1 variant acts through gain of function and together with an intronic variant in a downstream gene, SMAD3, points to defective TGFβR1 signaling as one of the biological perturbations increasing asthma risk. Our results increase the number of asthma variants and implicate genes with known role in T cell regulation, inflammation and airway remodeling in asthma pathogenesis.

Generation of a Human Allergic Mast Cell Phenotype from CD133+ Stem Cells.

Cultured human mast cells are a useful tool for research into innate immune responses as well as allergic mechanisms. Mast cells cultured from peripheral blood can provide information on immune mechanisms of known, selected individuals. With the method presented here, eight million mast cells can be cultured from ca. one million stem cells purified from one unit (450mL) of human peripheral blood. Culture with IgE and IL4 optimizes an allergic phenotype of the mast cells.

Asthma in children and adolescents: the ControL'Asma project.

The control of asthma is the objective of asthma management. However, it is difficult to obtain in clinical practice. The Italian Society of Allergy and Clinical Immunology promoted the nationwide project “ControL’Asma” to investigate the real situation in a group of children and adolescents with asthma. The preliminary outcomes demonstrated that many asthmatic subjects do not achieve adequate asthma control. Moreover, asthma in Italian children and adolescents was usually more frequent in males, had an early onset and allergic phenotype with very frequent rhinitis comorbidity, uncontrolled and partly controlled asthma affected about the half of subjects. However, this project suggested that the assessment of asthma symptom perception by VAS could be a reliable tool in the asthma management. (www.actabiomedica.it)

Risk Factors and Comorbidities Associated With the Allergic Rhinitis Phenotype in Children According to the ARIA Classification.

PurposeData are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study.MethodsWe enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed.ResultsThe prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77–15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40–40.74).ConclusionsModerate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.

Study and Follow-Up of Patients with Allergic Eosinophilic Esophagitis Phenotype

Study and Follow-Up of Patients with Allergic Eosinophilic Esophagitis Phenotype

Comparison of asthma phenotypes in OVA-induced mice challenged via inhaled and intranasal routes

BackgroundThe respiratory system is exposed to various allergens via inhaled and intranasal routes. Murine models of allergic lung disease have been developed to clarify the mechanisms underlying inflammatory responses and evaluate the efficacy of novel therapeutics. However, there have been no comparative studies on differences in allergic phenotypes following inhaled vs. intranasal allergen challenge. In this study, we compared the asthmatic features of mice challenged via different routes following allergen sensitization and investigated the underlying mechanisms.MethodsTo establish ovalbumin (OVA)-induced allergic asthma models, BALB/c mice were sensitized to 20 μg OVA with 1 mg aluminum hydroxide by the intraperitoneal route and then challenged by inhalation or intranasal administration with 5% OVA for 3 consecutive days. Cellular changes and immunoglobulin (Ig) E levels in bronchoalveolar lavage fluid (BALF) and serum, respectively, were assessed. Histological changes in the lungs were examined by hematoxylin and eosin (H&E) and periodic acid Schiff (PAS) staining. Levels of T helper (Th)2 cytokines including interleukin (IL)-4, -5, and -13 in BALF and epithelial cytokines including IL-25 and -33 in BALF and lung tissues were measured by enzyme-linked immunosorbent assay and western blotting. Airway hyperresponsiveness (AHR) was evaluated by assessing airway resistance (Rrs) and elastance (E) via an invasive method.ResultsOVA-sensitized and challenged mice showed typical asthma features such as airway inflammation, elevated IgE level, and AHR regardless of the challenge route. However, H&E staining showed that inflammation of pulmonary vessels, alveolar ducts, and alveoli were enhanced by inhaled as compared to intranasal OVA challenge. PAS staining showed that intranasal OVA challenge induced severe mucus production accompanied by inflammation in bronchial regions. In addition, Th2 cytokine levels in BALF and AHR in lung were increased to a greater extent by inhalation than by intranasal administration of OVA. Epithelial cytokine expression, especially IL-25, was increased in the lungs of mice in the inhaled OVA challenge group.ConclusionOVA-sensitized mice exhibit different pathophysiological patterns of asthma including expression of epithelial cell-derived cytokines depending on the OVA challenge route. Thus, some heterogeneous phenotypes of human asthma can be replicated by varying the mode of delivery after OVA sensitization.

Peripheral blood neutrophils and upregulated surface expression of interleukin-17 and CD177 in patients with bronchial asthma: an association with fungal allergy

BackgroundAsthma is a prevalent debilitating airway disease, with a tremendous effect worldwide. Fungi and their spores are identified as major culprits in allergic asthma (AA) etiology. Peripheral blood neutrophils and interleukin 17 (IL-17), which are considered crucial players in both bronchial asthma and host defense mechanisms against fungi, increase concomitantly; moreover, certain subsets of neutrophils express and even release IL-17.ObjectivesIn this study, we sought to determine the peripheral frequency of certain neutrophil subpopulations, expressing both CD177 and IL-17, among AA patients, particularly those with fungal allergy.MethodsThis observational study comprised 40 patients with AA (age range 19–60 years) and 20 age-matched and sex-matched healthy controls (age range 20–55 years). All patients had positive allergy skin prick test results, and accordingly, they were further subdivided into two groups (18 reactive to fungal allergens and 22 to other aeroallergens). The frequency of IL-17+CD177+ neutrophils in the peripheral blood was assessed by flow cytometry in all studied participants.ResultsThe authors observed significantly increased frequency of circulating IL-17+CD177+ neutrophils among AA patients (especially mild to moderate cases) compared with healthy controls (43.3±13.9 vs 15.3±4.8). On the contrary, and surprisingly, patients with fungal allergy and those without did not show any difference with respect to this neutrophil subpopulation (44.6±14.4 vs 42.2±13.7).ConclusionDespite limited sample size, we reported elevated IL-17+CD177+ neutrophil proportion in all AA, regardless of fungal aeroallergenicity. This observation points to a role played by this neutrophil subpopulation in asthma pathophysiology, especially the allergic phenotype, and hopefully offer a new therapeutic approach in asthma management.

Anaphylaxie à l’arachide par voie inhalée, à propos de 3 cas

Paradoxically, some dispute surrounds the risk of anaphylaxis through inhalation of peanut fragments and the literature contains only rare reports. Herein we describe 3 cases of inhaled peanut anaphylaxis in patients with a strong allergic phenotype: 2 cases of adolescents coming into contact with peanuts in public places (cinema, train) on two occasions, and a third case in a child receiving peanut immune tolerance induction (ITI). Following published cases of inhaled peanut anaphylaxis and complaints by allergic patients, protective measures have been taken by airlines and in certain countries. However, it has recently been asserted that peanuts are not volatile and that the risk of reaction to inhalation is minimal at most! However, we believe it is important to protect patients with a strong phenotype and high anaphylactic risk and for whom social situations (travel, outings, etc.) present a potential danger. We feel that ITI should be proposed, coupled with therapeutic education, even though the limits of ITI were evident in our third patient.

Полиморфные маркеры генов врожденного иммунитета у пациентов с аллергическим и неаллергическим фенотипом бронхиальной астмы

Полиморфные маркеры генов врожденного иммунитета у пациентов с аллергическим и неаллергическим фенотипом бронхиальной астмы

Intranasal nanoemulsion vaccine confers long-lasting immunomodulation and sustained unresponsiveness in a murine model of milk allergy.

Immunotherapy for food allergy requires prolonged treatment protocols and, in most cases, does not lead to durable modulation of the allergic immune response. We have demonstrated an intranasal (IN) nanoemulsion adjuvant that redirects allergen-specific Th2 responses toward Th1 and Th17 immunity, and protects from allergen challenge after only 2-4 monthly administrations. Here, we investigate the ability of this technology to provide long-term modulation of allergy in a murine model of cow's milk allergy. Six weeks after sensitization to bovine casein, mice received four, monthly IN immunizations with nanoemulsion formulated with casein. Protection from casein challenge was assessed at 4 and 16weeks after the final vaccine administration. The NE vaccine significantly blunted the physiological responses to allergen challenge, and this effect persisted for at least 16weeks. The protection from challenge was associated with the suppression of casein-specific Th2 immunity and induced Th1 and Th17 cytokines as well as induction of IL-10. Of interest, while immunized animals showed significantly decreased Th2 cytokine responses, cow's milk-specific IgE remained elevated in the serum at levels associated with reactivity in control sensitized animals. Protection was associated with suppressed mast cell activation and markedly reduced mast cell infiltration into the small intestine. The sustained unresponsiveness of at least 16weeks after vaccination suggests that the nanoemulsion vaccine alters the allergic phenotype in a persistent manner different from traditional desensitization, and this leads to long-term suppressive effects on allergic disease without eliminating serum IgE.