Severity Of Allergic Diseases Research Articles

Effect of heat, enzymatic hydrolysis and acid-alkali treatment on the allergenicity of silkworm pupa protein extract

Silkworm pupae are edible insects with high-quality nutrition in many Asian countries, but consumption of silkworm pupae can cause severe IgE-mediated allergic disease. The aim of this study was to investigate the effect of heat, enzymatic hydrolysis and acid-alkali treatment on the allergenicity of silkworm pupa protein extract (SPPE). Heating reduced the allergenicity of SPPE when the temperature was higher than 60 °C. Spectroscopy studies suggested an unfolded conformation of SPPE with heating, dependent on temperature and time. Enzymatic hydrolysis revealed that SPPE at 25 to 33 kDa contained pepsin- and trypsin-resistant allergens. The results of acid-alkali treatment suggested that low pH can promote hydrolysis of SPPE and decrease its allergenicity. Thus, heat, enzymatic hydrolysis and acid-alkali treatment can significantly decrease the allergenicity of SPPE, with heat-, enzyme- and acid-alkali–resistant allergens at 25 to 33 kDa SPPE. This study can help in the development of methods to prepare silkworm pupa protein.

Sex differences in group 2 innate lymphoid cell-dominant allergic airway inflammation

There were gender differences in the prevalence and severity of allergic diseases. Group 2 innate lymphoid cells (ILC2s) were recently reported to play a critical role in allergic diseases. We investigated the sex-dependent differences in ILC2-dominant allergic airway inflammation model using T\\B cell-deficient mice, and determined the gender differences of ILC2 levels in patients with asthma and allergic rhinitis. Female mice exhibited higher levels of inflammatory infiltration and large production of IL-5 and IL-13, especially for ILC2 levels compared to male mice with the induction of IL-33. However, no significant differences were found for the levels of circulating ILC2s between the genders of patients. The treatment of testosterone significantly decreased the intracellular type 2 cytokines in ILC2s and the proliferation of pure ILC2s in response to epithelial cytokines. Our study suggested the sex differences and the involvement of androgen on ILC2s in allergic diseases.

Allergic sensitization pattern of patients in Brazil

ObjectiveAllergic sensitization is one of the key components for the development of allergies. Polysensitization seems to be related to the persistence and severity of allergic diseases. Furthermore, allergic sensitization has a predictive role in the development of allergies. The aim of this study was to characterize the pattern of sensitization of atopic patients treated at different pediatric allergy referral centers in Brazil. MethodsA nation-wide transversal multicenter study collected data on patients attended in Brazil. Peripheral blood samples were collected to determine the serum levels of allergen-specific IgE. If allergen-specific IgE was higher than 0.1 kUA/L, the following specific components were quantified. ResultsA total of 470 individuals were enrolled in the study. Mite sensitization was the most frequent kind in all participants. A high frequency of sensitization to furry animals and grasses featured in the respiratory allergies. Regarding components, there was a predominance of sensitization to Der p 1 and Der p 2. It has been verified that having a food allergy, atopic dermatitis, or multimorbidity are risk factors for the development of more severe allergic disease. ConclusionStudies on the pattern of allergic sensitization to a specific population offer tools for the more effectual prevention, diagnosis, and treatment of allergic diseases. Sensitization to dust mites house was the most prevalent in the evaluated sample. High rates of sensitization to furry animals also stand out. Patients with food allergy, atopic dermatitis, or multimorbidity appear to be at greater risk for developing more severe allergic diseases.

Corneal fibroblasts: Function and markers

Corneal stromal keratocytes contribute to the maintenance of corneal transparency and shape by synthesizing and degrading extracellular matrix. They are quiescent in the healthy cornea, but they become activated in response to insults from the external environment that breach the corneal epithelium, with such activation being associated with phenotypic transformation into fibroblasts. Corneal fibroblasts (activated keratocytes) act as sentinel cells to sense various external stimuli—including damage-associated molecular patterns derived from injured cells, pathogen-associated molecular patterns of infectious microorganisms, and inflammatory mediators such as cytokines—under pathological conditions such as trauma, infection, and allergy. The expression of various chemokines and adhesion molecules by corneal fibroblasts determines the selective recruitment and activation of inflammatory cells in a manner dependent on the type of insult. In infectious keratitis, the interaction of corneal fibroblasts with various components of microbes and with cytokines derived from infiltrated inflammatory cells results in excessive degradation of stromal collagen and consequent corneal ulceration. Corneal fibroblasts distinguish between type 1 and type 2 inflammation through recognition of corresponding cytokines, with their activation by type 2 cytokines contributing to the pathogenesis of corneal lesions in severe ocular allergic diseases. Pharmacological targeting of corneal fibroblast function is thus a potential novel therapeutic approach to prevention of excessive corneal stromal inflammation, damage, and scarring.

Biologic Use in Allergic and Asthmatic Children and Adolescents During the COVID-19 Pandemic.

Background: Biologics are the cornerstone of therapy in children and adolescents with severe or uncontrolled allergic diseases, such as asthma, atopic dermatitis, and chronic urticaria. Since the World Health Organization (WHO) declared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection a pandemic in March 2020, some scientific societies have released statements on the use of biologics in allergic children and adolescents. Materials and Methods: Given the very limited data in Italy on use of biological therapies in allergic children and adolescents during the coronavirus disease 2019 (COVID-19) pandemic, a multicenter observational nationwide survey was conducted to collect this information. The 11-question survey was designed to determine (1) the number of allergic children and adolescents treated with omalizumab, mepolizumab, or dupilumab for asthma, atopic dermatitis, and chronic urticaria; (2) the number of these patients who developed COVID-19; and (3) severity of COVID-19 symptoms. Twenty pediatric centers participated, and data were collected from February to April 2020. Results: Three hundred eight children and adolescents (mean age 12.8 years, 161 males) were treated with biologics. Only 3 subjects (1%) who had been treated with omalizumab experienced paucisymptomatic COVID-19, but those symptoms promptly resolved. Of the 9 patients treated with mepolizumab, none had COVID-19 or asthma exacerbations. Of the 6 asthmatic subjects and 7 patients with chronic urticaria treated with dupilumab, none had COVID-19. Also, there was no worsening of the underlying disease. Conclusion: These very preliminary outcomes suggest that continuing biologics seem to be safe. Therefore, biologics could be continued in patients with severe allergic diseases, but withheld once contracted COVID-19.

Association of air pollution with severe ocular allergic inflammatory diseases

Association of air pollution with severe ocular allergic inflammatory diseases

Effects of Intervention on Home-Based Environmental Counselling for Children with Severe Allergic Diseases

Background/Objectives: Home-based environmental management is the key to managing allergic diseases. This study identified the effects of environmental counseling intervention in children with atopic dermatitis and respiratory diseases.Methods/Statistical analysis: The participants were 198 children with allergic diseases who participated in the study in 2016. In 2017, 66 children with severe allergic diseases in a follow-up study were selected. We ultimately analyzed the effect of environmental counseling in 26 children. To assess the effect of the intervention, the research team conducted a pre-test (baseline) and post-test (follow-up) twice. Trans-epidermal water loss (TEWL) and scoring atopic dermatitis (SCORAD) index were used to assess atopic dermatitis (AD) and forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), immunoglobulin E (IgE), and eosinophil counts were used to assess respiratory diseases.Findings: In children with AD, the baseline and follow-up SCORAD index values were 40.33 and 31.15 points, respectively. In children with respiratory diseases, the baseline and follow-up FEV1 values were 77.77 and 87.53 points, respectively; baseline and follow-up FVC values were 81.38 and 95.54 points, respectively; baseline and follow-up IgE values were 520.86 and 481.37 points, respectively; and baseline and follow-up eosinophil values were 4.97 and 4.42 points, respectively. Thus, home-based environmental counseling decreased FEV1 and FVC values.Improvements/Applications: Patients with respiratory diseases treated with home-based environmental counseling exhibited positive changes in FEV1 and FVC values. Home-based indoor environmental counseling is regularly needed to manage respiratory diseases. The parents of children with respiratory diseases must try to minimize their exposure to harmful substances indoors

Phénotypes des maladies allergiques vus par l’allergologie moléculaire : les leçons des cohortes du monde

Molecular components of allergens shows the diversity of the reactivity of allergens and their components according to the environment, for example the main allergies are towards animal dander and pollens in Sweden, cockroach in États-Unis and house dust mites in France and in England. Food allergies follow these same rules, for example the major problem is peanut in English spoken countries and cow's milk in France. The classification of allergen molecules into different families of proteins (depending on their structure and function) can help to predict the development local or systemic reactions. Members of the same protein family can share similar IgE épitopes, with the risk of strong cross-reactivity response. For allergy to food allergens, a stable allergenic component toward the heat is associated with greater risk of development of severe allergic reaction. For inhaled allergens, specific IgE towards major allergenic compounds were associated with the severity of allergic disease. Multiple sensitizations towards native allergens but also molecular allergens are associated with the severity of the allergy for inhaled but also food allergens in the word.

Quality In Allergology.

High-quality treatment of patients suffering from allergies should be a first priority of ENT specialists. In daily routine of otolaryngologists, allergic diseases play a significant role and have to be diagnosed and treated competently. A multitude of guidelines provide a clear corridor for identification of suitable methods. The most important sensitization tests such as skin tests and the determination of specific IgE in the serum lay the foundations of allergy diagnostics. Nasal provocation tests with allergens as most important and most frequently applied allergen provocation tests can be performed especially by highly qualified ENT specialists. They allow the determination of the clinical relevance of single allergens.Beside pharmacotherapy and avoidance of allergens, the allergen-specific immunotherapy has a central position in the treatment of allergy diseases. Also in this context, correct indication and targeted selection of the pharmaceutics lead to an increased treatment quality.In particular complex or severe allergic diseases require specialized and even highly specialized treatment. In Germany, structured requirements for establishing Comprehensive Allergy Centers have been developed. The involvement of otolaryngology in the further development of such centers should be improved.Sound allergy education and training are the basis for competence and quality of the treatment of allergy patients. In medical studies, allergology is currently underrepresented. In specialization, some basic aspects of allergies are taken into account. The medical education for the additional specialization in allergology is currently changing; it is intended to be simplified but this might lead to devaluation. A full speciality of allergology does currently not exist in Germany.In particular in the areas of allergy training, allergy research, and in the cooperation of ENT specialists in highly specialized allergy centers, an enormous potential for improvement is seen for the discipline of otolaryngology.

Human Mast Cell Proteome Reveals Unique Lineage, Putative Functions, and Structural Basis for Cell Ablation

Mast cells are rare tissue-resident cells of importance to human allergies. To understand the structural basis of principle mast cell functions, we analyzed the proteome of primary human and mouse mast cells by quantitative mass spectrometry. We identified a mast-cell-specific proteome signature, indicative of a unique lineage, only distantly related to other immune cell types, including innate immune cells. Proteome comparison between human and mouse suggested evolutionary conservation of core mast cell functions. In addition to specific proteases and proteins associated with degranulation and proteoglycan biosynthesis, mast cells expressed proteins potentially involved in interactions with neurons and neurotransmitter metabolism, including cell adhesion molecules, ion channels, and G protein coupled receptors. Toward targeted cell ablation in severe allergic diseases, we used MRGPRX2 for mast cell depletion in human skin biopsies. These proteome analyses suggest a unique role of mast cells in the immune system, probably intertwined with the nervous system.

Mechanisms of allergy and adult asthma.

Allergic asthma reflects the interplay between inflammatory mediators and immune, airway epithelial, and other cells. This review summarizes key insights in these areas over the past year. Key findings over the past year demonstrate that epithelial cells mediate tight junction breakdown to facilitate the development of asthma-like disease in mice. Innate lymph lymphoid cells (ILC), while previously shown to promote allergic airway disease, have now been shown to inhibit the development of severe allergic disease in mice. Fibrinogen cleavage products (previously shown to mediate allergic airway disease and macrophage fungistatic immunity by signaling through Toll-like receptor 4) have now been shown to first bind to the integrin Mac-1 (CD11c/CD18). Therapeutically, recent discoveries include the development of the antiasthma drug PM-43I that inhibits the allergy-related transcription factors STAT5 and STAT6 in mice, and confirmatory evidence of the efficacy of the antifungal agent voriconazole in human asthma. Studies over the past year provide critical new insight into the mechanisms by which epithelial cells, ILC, and coagulation factors contribute to the expression of asthma-like disease and further support the development antiasthma drugs that block STAT factors and inhibit fungal growth in the airways.

Allergic inflammation is initiated by IL-33-dependent crosstalk between mast cells and basophils.

IgE-primed mast cells in peripheral tissues, including the skin, lung, and intestine, are key initiators of allergen-triggered edema and inflammation. Particularly in severe forms of allergy, this inflammation becomes strongly neutrophil dominated, and yet how mast cells coordinate this type of response is unknown. We and others have reported that activated mast cells––a hematopoietic cell type––can produce IL-33, a cytokine known to participate in allergic responses but generally considered as being of epithelial origin and driving Type 2 immune responses (e.g., ILC2 and eosinophil activation). Using models of skin anaphylaxis, our data reveal that mast cell-derived IL-33 also initiates neutrophilic inflammation. We demonstrate a cellular crosstalk mechanism whereby activated mast cells crosstalk to IL-33 receptor–bearing basophils, driving these basophils to adopt a unique response signature rich in neutrophil-associated molecules. We further establish that basophil expression of CXCL1 is necessary for IgE-driven neutrophilic inflammation. Our findings thus unearth a new mechanism by which mast cells initiate local inflammation after antigen triggering and might explain the complex inflammatory phenotypes observed in severe allergic diseases. Moreover, our findings (i) establish a functional link from IL-33 to neutrophilic inflammation that extends IL-33–mediated biology well beyond that of Type 2 immunity, and (ii) demonstrate the functional importance of hematopoietic cell–derived IL-33 in allergic pathogenesis.

Effect of ethnicity on the prevalence of allergic disease

Differences in the prevalence and severity of allergic diseases exist among racial and ethnic groups. However, influence of popula tion admixing on allergic disease has not been studied. This review aimed to review studies in the literature which examined the dif ference in the prevalence and severity of allergic disease among populations with different ancestry and to discuss the effect of population admixing on the occurrence and severity of allergic disease. Several studies have shown that the prevalence and sever ity of asthma, allergic rhinitis, and atopic dermatitis were different according to ethnicity. However, there have been only a few stud ies evaluating the effect of population admixing on allergic disease. Ethnicity and environmental effect should be considered in the diagnosis and treatment of allergic disease. (Allergy Asthma Respir Dis 2020;8:114-118)

Biotherapies and ocular surface

AbstractThe pathophysiology of ocular surface diseases is better understood today. Several targets have been identified for their treatment, and currently available biotherapies are already used in clinical practice for selected cases.In severe allergic diseases: Omalizumab (Xolair®) is a systemic anti‐IgE treatment that suppresses the allergic response. It has been successfully used in vernal and atopic keratoconjunctivitis Dupilumab (Dupixent®) is an anti‐IL4/IL13 systemic therapy indicated for severe atopic dermatitis. It has been used in atopic keratoconjunctivitis patients. It also has frequent ocular side effects such as conjunctivitis and blepharitis In severe dry eye: Lifitegrast (Xiidra®) is a LFA1 receptor inhibitor eye drop that prevents inflammatory cells to bind to the adhesion molecule ICAM 1. It has been approved in the US for the treatment of dry eye. The effects on symptoms seem to be superior to those of topical cyclosporine. In mucous membrane pemphigoid: Rituximab (Mabthera®) is a systemic anti CD20 antibody that targets B and pre‐B lymphocytes. It has shown very interesting results in severe cases.

Air pollution significantly associated with severe ocular allergic inflammatory diseases

Ambient air pollution is a well-recognized risk for various diseases including asthma and heart diseases. However, it remains unclear whether air pollution may also be a risk of ocular allergic diseases. Using a web-based, nation-wide, cross-sectional study design, we examined whether the level of ambient air pollution is significantly associated with the prevalence of ocular allergic diseases. A web-based questionnaire was posted to invite the participants who are members of the Japan Ophthalmologist Association and their family members. The answers from 3004 respondents were used to determine whether there were significant associations between the level of the pollutants and the prevalence of ocular allergic diseases. The study period was between March to May 2017. The data of the air pollutants during 2012 to 2016 were obtained from the National Institute for Environmental Studies. The prevalence of allergic diseases was calculated by post stratification and examined for significant associations with the level of pollutants using multiple logistic regression analyses. The prevalence of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, atopic keratoconjunctivitis (AKC), and vernal keratoconjunctivitis (VKC) in Japan was 45.4%, 14.0%, 5.3%, and 1.2%, respectively. The high prevalence of the severe forms of allergic conjunctivitis, including AKC and VKC, were significantly associated with the levels of the air pollutants. The prevalence of AKC was significantly associated with the levels of NO2 with an odds ratio (OR) of 1.23 (per quintile). The prevalence of VKC was significantly associated with the levels of NOx and PM10 with ORs of 1.72 and 1.54 respectively. The significant associations between the prevalence of AKC and VKC and the levels of air pollutants indicate that clinicians need to be aware that air pollutants may pose serious risks of vision threatening severe ocular allergy.

Topical tacrolimus for allergic eye diseases.

The spectrum of allergic eye diseases includes a variety of conditions, each characterized by complex immunopathologies.Antiallergic drugs, such as antihistamines and mast cell stabilizers, are often insufficient without concomitant topical corticosteroid treatment. The chronic course of the more severe allergic eye diseases, such as vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC), limits the treatment with topical corticosteroids to short courses. In addition, topical corticosteroid treatment puts patients at high risk of developing severe ocular complications, particularly during childhood when VKC most frequently occurs.The immunopathology of chronic diseases, such as VKC and AKC, involves predominantly T lymphocytes, and as such, immunomodulators that inhibit T-cell activation seem to be the appropriate treatment for these chronic diseases. In the past years, there is an increased incidence of managing chronic allergic eye diseases with the immunomodulator tacrolimus. The current review presents an update of the recent clinical experience with topical tacrolimus for the management of chronic allergic eye diseases. Topical tacrolimus significantly improves the symptoms and signs of the various forms of chronic allergic eye disease. Recent studies also demonstrate the efficacy of low concentrations of topical tacrolimus for VKC.Early medical treatment with topical tacrolimus can also prevent the development of serious ocular complications of VKC, such as shield ulcers or limbal stem cell deficiency. Topical tacrolimus has significantly changed the management approaches in severe and chronic allergic eye diseases and has minimized the need for topical corticosteroids.

Serum IL-1\u03b2 can be a biomarker in children with severe persistent allergic rhinitis

BackgroundAllergic rhinitis (AR) is one of the most common diseases globally and usually persists throughout life. In the present study, we aimed to determine whether the expression of inflammatory biomarkers has a relationship with the severity of allergic rhinitis and with comorbid asthma or other allergic diseases in children.MethodsFor diagnosis of AR, the skin prick test was performed to measure the responses to 18 allergens. Blood levels of eosinophils and immunoglobulin E (IgE) were examined. We classified the patients into 2 groups based on the severity of the condition as Group 1 [intermittent AR (IAR) or mild persistent AR (PAR)] and Group 2 (moderate to severe PAR). To determine the expression of inflammatory biomarkers, in serum and several biomarkers (caspase-1, IL-1β, CCL-11, CCL-24 and IL-33) were measured in the serum using enzyme-linked immunosorbent assay (ELISA). Additionally, we analyzed the correlation between clinical variables and the expression of biomarkers (eosinophils count, IL-1β and CCL-24) and the severity of AR.ResultsWe found that eosinophils count, IL-1β, a marker of activation of inflammasomes, and CCL-24 were significantly increased in the moderate to severe PAR group (p = 0.008, p = 0.003, p = 0.039). Additionally, the expressions of eosinophil count, IL-1β and CCL-24 were significantly higher in patients with active asthmatic symptoms than in those without these conditions. On univariate analysis, allergic rhinitis in sibling, paternal allergic rhinitis, high expression of eosinophils count, IL-1β and CCL-24, history of active asthma and atopy correlated with severity of AR. Multivariate analysis showed only paternal allergic rhinitis and high expression of IL-1β as significant risk factors of moderate to severe PAR with 6.4 fold and 4.7 fold-increase in risk, respectively (p = 0.011 and p = 0.030).ConclusionIn conclusion, this study provides the first evidence that an excessive release of biologically active IL-1β may promote inflammation in severe PAR. It demonstrates that IL-1β can be a biomarker for active allergic diseases such as AR, asthma, and atopy. Moreover, this finding suggests that IL-1B should be investigated as a therapeutic target in severe PAR and other allergic diseases.

Omalizumab in children with severe allergic disease: a case series

BackgroundCurrently, severe allergic asthma and food allergy in children represent an important public health problem with medical, psychosocial and economic impacts. Omalizumab is a humanized monoclonal anti-IgE antibody, approved for refractory allergic asthma and chronic urticaria. It has been widely used in clinical practice as add-on therapy in patients with severe uncontrolled allergic asthma. In recent years there has seen the emergence of an allergic epidemic with increasing food allergy, which represents the main cause of anaphylaxis in children. The standard of care for food allergy is strictly dietary allergen avoidance and emergency treatment, but recent clinical trials have suggested that omalizumab may have a role to play as an adjuvant to oral immunotherapy (OIT). We present a case series of patients treated at our institution with omalizumab for severe allergic asthma and food allergy.MethodsPatients received omalizumab according to a standard reference nomogram after failing standard therapies. In children with comorbid severe food allergy, omalizumab was administered in conjunction with an oral immunotherapy protocol.ResultsOmalizumab was effective in controlling symptoms of allergic asthma, allergic rhinitis and rhinosinusitis, but not eosinophilic esophagitis, while aiding successful oral desensitization of comorbid severe food allergies.ConclusionsOmalizumab appears to be an excellent therapeutic option in children with inadequately controlled severe allergic asthma, allergic rhinitis and rhinosinusitis, with or without food allergy.

House Dust Mite Allergy Under Changing Environments.

Environmental variations induced by industrialization and climate change partially explain the increase in prevalence and severity of allergic disease. One possible mechanism is the increase in allergen production leading to more exposure and sensitization in susceptible individuals. House dust mites (HDMs) are important sources of allergens inducing asthma and rhinitis, and experimentally they have been demonstrated to be very sensitive to microenvironment modifications; therefore, global or regional changes in temperature, humidity, air pollution or other environmental conditions could modify natural HDM growth, survival and allergen production. There is evidence that sensitization to HDMs has increased in some regions of the world, especially in the subtropical and tropical areas; however, the relationship of this increase with environmental changes is not so clear as has reported for pollen allergens. In this review, we address this point and explore the effects of current and predicted environmental changes on HDM growth, survival and allergen production, which could lead to immunoglobulin E (IgE) sensitization and allergic disease prevalence. We also assess the role of adjuvants of IgE responses, such as air pollution and helminth infections, and discuss the genetic and epigenetic aspects that could influence the adaptive process of humans to drastic and relatively recent environmental changes we are experiencing.

Effects of diet on the childhood gut microbiome and its implications for atopic dermatitis

Effects of diet on the childhood gut microbiome and its implications for atopic dermatitis