Specific Allergen Research Articles

Prevalence of sensitization to specific allergens in allergic patients in Beijing, China: A 7-year retrospective study.

Knowledge of the prevalence of common sensitizing allergens may aid in overall management of allergic disease in a specified area. The aim of this study was to identify and analyse the prevalence of common inhaled and food sensitizing allergens in Beijing. This was a retrospective study, analysing demographic data and serum sIgE antibody test results from 59057 outpatients who presented to Beijing TongRen Hospital, from January 2013 to December 2019. 28879 patients (48.9%) showed positive sIgE test results; with significantly more males aged under 16 years sensitized to at least one allergen than females, and most patients (53.62%) were sensitized to multiple allergens. The first inhaled sensitizing allergens was Artemisia grass (11910 (41.24%)); and the first food allergens was crab (3547 (12.28%)). For Artemisia sensitized patients, sIgE levels were mostly at level 5. The number of patients with ragweed allergy is increasing year by year. The detection rates for sIgE to Artemisia, common ragweed, and Humulus grass allergens were significantly higher in August and September. R package ggplot2 analysis, demonstrated strong correlations between tree allergens and common ragweed and Humulus grass allergens (phi coefficients = 0.50 and 0.46, respectively; both P < 0.01). The prevalence of sensitization to different allergens in Beijing showed Artemisia grass was the most commonly inhaled sensitizing allergen, and the number of patients with ragweed grass allergy was increasing by year.

Influence of Antihistamines on Basophil Activation Test in Food Allergy to Milk and Egg.

Background: The basophil activation test (BAT) is used to improve the accuracy of food allergy diagnosis. To date, the influence of antiallergic drugs on BAT reactivity is poorly investigated. The aim of the study was to investigate if BAT results were influenced by antihistamine intake for 3 months in a cohort of patients with IgE-mediated food allergy to milk or egg. Methods: A retrospective, single-center, observational study was performed. We enrolled subjects with history of hypersensitivity reaction after specific food ingestion, positive skin prick tests and specific IgEs, concomitant allergic rhinitis, and, contraindication to the double-blind, placebo-controlled food challenge due to personal history of systemic reactions related to the ingestion of culprit food. Validated allergens (α-lactoalbumin, β-lactoglobulin, casein, egg white, and yolk) for BAT were used. Results: Thirty-nine patients with well-documented food symptoms and positive allergological workup were included in the study. BAT was positive in 29 patients. The mean percentages of CD63+ expression to specific culprit allergen did not change after the administration of drugs. Conclusions: This was the first study assessing the effects of oral antihistamines on basophil reactivity in cow’s milk and egg food allergy. Antihistamines do not interfere with BAT results.

Quality of life of patients undergoing specific allergen immunotherapy in allergic rhinitis

Although allergic diseases have been known since antiquity, both their understanding and systematics came later. The World Allergy Organization (WAO) defines the phenomenon of atopy as a predisposition of a person or family to the uncontrolled synthesis and release of IgE antibodies. Allergic rhinitis (AR) is one of the most important clinical diseases of rhinitis (NN, rhinitis). AR significantly reduces the quality of life, tends to increase, and its consequences may be life-threatening diseases. The aim of the study is to determine the quality of life of patients who underwent specific allergen immunotherapy in allergic rhinitis. The study was conducted at the Center for Specialist Allergology in Lublin between October 2018 - February 2019. The study covered a group of 157 patients. The diagnostic method used was a questionnaire. The first research tool was own questionnaire consisting of 31 questions. The second tool was the standardized questionnaire, the Polish version of the SF-36 Quality of Life Questionnaire. Studies have shown statistically significant changes in the symptoms of before and after immunotherapy, which means improving the quality of life and reducing the severity of symptoms and problems of respondents after therapy. The respondents were not in the best of health (50%). Over 50% of respondents said that the immunotherapy process significantly reduced personal / family expenses for treatment associated with allergic rhinitis. The conducted process of specific allergen immunotherapy improved the quality of life of respondents by increasing awareness of the quality of life through the prism of health change in relation to the general indicator in the area of mental problems by reducing their nuisance value more than in the area of somatic symptoms.

Improved pulmonary function test (PFT) after 1 one year of Sublingual Immunotherapy (SLIT) in unison with pharmacotherapy in mild allergic asthmatics

BackgroundAllergen immunotherapy (AIT) is a promising treatment for allergic disease that induces immunological tolerance through the administration of specific allergens. The study of AIT is in its early stage and its clinical effects are not well elucidated. The present study was aimed at determining the effect of AIT on pulmonary function and serum variables of mild allergic asthma patients. MethodsA total of 80 patients with mild allergic asthma were recruited for the study. Allergen Specific Immunotherapy was administered in the form of Sublingual Immunotherapy and consisted of a build up phase followed by a maintenance phase (six months each respectively). Total serum IgE and vitamin D levels were quantified by ELISA. The percent eosinophill count was determined by cell analyzers. Pulmonary function test was performed at the baseline and after the end of study period. Subjective symptom score was recorded in the form of asthma control questionnaire score. ResultsThere was a significant increase in the pre FEV1% and pre FEV1/FVC post AIT administration. A significant decrease in the total serum IgE was found post AIT. A decrease in Asthma control Questionnaire (ACQ) scores indicated an improvement in clinical symptoms. Besides there was a significant effect on ICS discontinuation after AIT. ConclusionThe study supports SLIT as an effective treatment for Immunomodulation in mild allergic asthmatics besides it gives us significant information regarding the safety and efficacy of SLIT in such patients.

Basophil activation test in allergy diagnostics

The prevalence of allergic diseases in Poland and in the world continues to rise in recent years. The most commonly used methods for diagnosing IgE – dependent allergies are skin prick testing (SPT) and assessment of specific IgE (sIgE) directed against specific allergens. However, both methods have some disadvantages and the obtained results may be inconsistent. In particular, routine diagnostic tests are not always effective for some drugs and foods. Consequently, additional laboratory tools should be used. Basophil activation test (BAT) based on flow cytometry is a promising diagnostic method. The present paper demonstrates the usefulness and effectiveness of BAT protocols in allergy diagnosis in scientific research. In comparison to routinely used diagnostic methods, BAT is an expensive and complicated laboratory tool. However, it offers the possibility to efficiently and effectively recognize allergies. Introducing BAT into routine diagnostics in allergology is problematic because this method has not yet been standardized and validated. Therefore, there is a justified need to continue research in this field. If standardized and validated, BAT may offer a reasonable improvement in allergy diagnostics in the future.

Role of IgE-FcεR1 in Pathological Cardiac Remodeling and Dysfunction.

Immunoglobulin E (IgE) belongs to a class of immunoglobulins involved in immune response to specific allergens. However, the roles of IgE and IgE receptor (FcεR1) in pathological cardiac remodeling and heart failure are unknown. Serum IgE levels and cardiac FcεR1 expression were assessed in diseased hearts from human and mouse. The role of FcεR1 signaling in pathological cardiac remodeling was explored in vivo by FcεR1 genetic depletion, anti-IgE antibodies, and bone marrow transplantation. The roles of the IgE-FcεR1 pathway were further evaluated in vitro in primary cultured rat cardiomyocytes and cardiac fibroblasts (CFs). RNA sequencing and bioinformatic analyses were used to identify biochemical changes and signaling pathways that are regulated by IgE/FcεR1. Serum IgE levels were significantly elevated in patients with heart failure as well as in 2 mouse cardiac disease models induced by chronic pressure overload via transverse aortic constriction and chronic angiotensin II infusion. Interestingly, FcεR1 expression levels were also significantly upregulated in failing hearts from human and mouse. Blockade of the IgE-FcεR1 pathway by FcεR1 knockout alleviated transverse aortic constriction- or angiotensin II-induced pathological cardiac remodeling or dysfunction. Anti-IgE antibodies (including the clinical drug omalizumab) also significantly alleviated angiotensin II-induced cardiac remodeling. Bone marrow transplantation experiments indicated that IgE-induced cardiac remodeling was mediated through non-bone marrow-derived cells. FcεR1 was found to be expressed in both cardiomyocytes and CFs. In cultured rat cardiomyocytes, IgE-induced cardiomyocyte hypertrophy and hypertrophic marker expression were abolished by depleting FcεR1. In cultured rat CFs, IgE-induced CF activation and matrix protein production were also blocked by FcεR1 deficiency. RNA sequencing and signaling pathway analyses revealed that transforming growth factor-β may be a critical mediator, and blocking transforming growth factor-β indeed alleviated IgE-induced cardiomyocyte hypertrophy and cardiac fibroblast activation in vitro. Our findings suggest that IgE induction plays a causative role in pathological cardiac remodeling, at least partially via the activation of IgE-FcεR1 signaling in cardiomyocytes and CFs. Therapeutic strategies targeting the IgE-FcεR1 axis may be effective for managing IgE-mediated cardiac remodeling.

Restaurant disclosure of food allergens: Analysis and economic implications

Research suggests that between 20–30% of consumers self-identify as having some form of food allergy or sensitivity and demand for allergy-safe foods is growing. European Union regulations require restaurants to inform diners of the presence of 14 primary food allergens. The method of disclosure, however, is left to the discretion of the restaurant and may include verbal communication, menu labels, or separate informational pamphlets. Despite these requirements, 74% of allergen related food incidents arise from the non-prepackaged (restaurant) environment. Individuals with allergens, therefore, may avoid restaurants or intentionally seek out, especially in the tourism context, venues with publicly disclosed allergen prevention protocols. Due to group effects and social media's ability to channel consumers, implementing allergy-friendly practices could substantially increase restaurant profits. This research examines the performance of the restaurant industry in leading tourist destinations in Croatia with respect to self-disclosure of potential food allergens. Menus, accompanying websites and social media reviews of 973 restaurants across 43 locations were analyzed. Results indicate that very few restaurants have taken affirmative steps to disclose food allergens on their websites (1.3% of English and 0.8% of Croatian websites). Of the subset of restaurants with on-line menus, 6.5% disclosed specific food allergens. In contrast, third-party social media reviews of 24.6% of the restaurants included some statement relating to food allergens. Based on the results, this paper suggests strategies for improved food allergen communication. Specifically, restaurants should make greater efforts to affirmatively disclose allergen information on their websites and monitor social media reviews. Very few restaurants responded to consumer comments, thereby allowing others to dictate the narrative. In light of the strong consumer interest and relatively weak self-disclosure efforts, the hospitality industry has a ready opportunity to attract new consumers by moving beyond regulatory minimums through enhanced allergen communication efforts and social media engagement.

A Systematic Review of Food Allergy: Nanobiosensor and Food Allergen Detection.

Several individuals will experience accidental exposure to an allergen. In this sense, the industry has invested in the processes of removing allergenic compounds in food. However, accidental exposure to allergenic proteins can result from allergenic substances not specified on labels. Analysis of allergenic foods is involved in methods based on immunological, genetic, and mass spectrometry. The traditional methods have some limitations, such as high cost. In recent years, biosensor and nanoparticles combined have emerged as sensitive, selective, low-cost, and time-consuming techniques that can replace classic techniques. Nevertheless, each nanomaterial has shown a different potential to specific allergens or classes. This review used Preferred Reporting Items for Systematic Reviews and the Meta-Analysis guidelines (PRISMA) to approach these issues. A total of 104 articles were retrieved from a standardized search on three databases (PubMed, Scopus and Web of Science). The systematic review article is organized by the category of allergen detection and nanoparticle detection. This review addresses the relevant biosensors and nanoparticles as gold, carbon, graphene, quantum dots to allergen protein detection. Among the selected articles it was possible to notice a greater potential application on the allergic proteins Ah, in peanuts and gold nanoparticle-base as a biosensor. We envision that in our review, the association between biosensor and nanoparticles has shown promise in the analysis of allergenic proteins present in different food samples.

15731 Allergic contact dermatitis in patients with atopic dermatitis: A 10-year retrospective review

Allergic contact dermatitis (ACD) is prevalent in 20% of patients with atopic dermatitis (AD). We performed a retrospective chart review of patients patch tested at the Massachusetts General Hospital from 2007 to 2016 to investigated the rate of ACD among patients with AD and those without AD. We further stratified by adult or pediatric (<18 years). Statistical analyses were carried out by contingency tables using χ2 and Fisher exact tests. A total of 2373 patients were patch tested: 695 (29.3%) in AD group and 1678 (70.7%) in non-AD group. One or more positive reactions were observed in 424 (61.0%) patients in AD group compared with 1003 (59.8%) patients in non-AD group. When stratified by age, there was no significant difference in ACD prevalence in the patients with AD and without AD. Nickel, Fragrance Mix 1, and Balsam of Peru were the top allergens in both groups. Six allergens were statistically different between AD and non-AD groups. Patients with AD had an increased sensitization to lanolin (amerchol-L101), quaternium-15, glyceryl monothioglycolate and dialkyl thiourea compared with non-AD patients. Patients with AD were noted to have decreased sensitization to neomycin and cinnamic aldehyde. Patients with AD were equally likely to develop contact sensitization as non-AD patients, regardless of age. Exposures to personal care products, such as lanolin containing moisturizers, in patients with AD may play a role in sensitization to specific allergens. Clinicians should consider patch testing patients with AD who report worsening of dermatitis or AD that does not respond to usual treatment.

Bos d 11 in baked milk poses a risk for adverse reactions in milk-allergic patients.

Patients are commonly challenged with foods containing baked milk, for example muffins, yet little is known about the specific allergen content of muffins used in milk challenges or of the effect that baking has on allergenicity. Our objective was to compare the levels of major milk allergens in uncooked and baked muffins using monoclonal immunoassays and IgE antibody binding before and after baking. Uncooked and baked muffins were prepared using recipes from Mount Sinai and Imperial College. Allergen levels were compared by ELISA for Bos d 5 (β-lactoglobulin) and Bos d 11 (β-casein). IgE reactivity was assessed using sera from milk-sensitized donors in direct binding and inhibition ELISA. Bos d 5 was reduced from 680µg/g in uncooked muffin mix to 0.17µg/g in baked muffins, representing a >99% decrease after baking. Conversely, Bos d 11 levels in baked muffin remained high and only decreased by 30% from a mean of 4249µg/g in uncooked muffin mix to 2961µg/g when baked (~181mg Bos d 11 per muffin). Baked muffins retained ~70% of the IgE binding to uncooked muffin mix. Baked muffin extract inhibited IgE binding to uncooked muffin mix by up to 80%, demonstrating retention of in vitro IgE reactivity. High levels of Bos d 11 in baked muffins pose a risk for adverse reactions, especially in patients who have high anti-casein IgE antibodies.

Non-allergic severe asthma: is it really always non-allergic? The IDENTIFY project

BackgroundThis differential diagnosis of allergic vs non-allergic asthma is typically made on the basis of sensitization to allergens, such that absence of sensitization could result in a patient being managed as having non-allergic asthma. In Germany, the number of specific allergen tests is limited and non-standardized (across clinicians and laboratories), with the potential for false negative diagnoses. IDENTIFY aimed to gain data on sensitizations toward aeroallergens in patients with severe asthma who had tested negative to perennial aeroallergens in previous tests.MethodsThis was a single visit, non-randomized, non-interventional study conducted in 87 centers across Germany. The only inclusion criteria were that patients had to be adults (at least 18 years of age) with a diagnosis of severe asthma (receiving at least Global Initiative for Asthma Step IV therapy), and who had previously tested negative to perennial aeroallergens. Patients were then tested for sensitization to a panel of 35 perennial aeroallergens, with positive sensitization indicated by CAP ≥ 0.35 kU/L.ResultsOf 588 patients recruited, 454 had complete and valid data, and had previously tested negative to perennial aeroallergens. Overall, 43.6% of the analyzed patients tested positive for at least one of the included aeroallergens, with 18.7% testing positive for three or more, and 4.2% positive for more than ten. The five most common sensitizations were to Staphylococcus aureus enterotoxin B, Aspergillus fumigatus, Candida albicans, Dermatophagoides farinae, and Rhizopus nigricans, each of which tested positive in at least 9.7% of the population.ConclusionsIn this group of patients being managed as having non-allergic asthma (and who had all previously tested negative to perennial aeroallergens), a high proportion tested positive to a broad panel of aeroallergens. A diagnosis of allergic asthma therefore cannot be excluded purely on the basis of standard aeroallergen panels.

M051 ALLERGIC DISEASE AND THE HUMAN MICROBIOME: A CASE OF SYMPTOM REGRESSION WITH ANTIBIOTIC USE

The incidence of allergic disease has increased over the last decade with correlations to changes in the human microbiome. The microbiome plays an active role in the immune system with dysbiosis associated with increased chronic inflammatory disease. This case exhibits the potential relationship between respiratory allergic symptoms and the gut flora. It explores the idea of antibiotic use to alter the body’s reaction to specific allergens.

Specific Dermatophagoides farinae extract for canine immunotherapy.

Canine atopic dermatitis (cAD) is a pruritic allergic skin disease most often caused by Dermatophagoides farinae. Differences in the sensitization profile to D.farinae have been reported between people and dogs. However, allergic dogs traditionally have been treated with extracts intended for human immunotherapy. To develop a specific allergen immunotherapy for veterinary practice enriched in canine major allergens and to demonstrate its in vitro efficacy. Twenty privately owned dogs, clinically diagnosed with cAD, and three healthy dogs. A veterinary D.farinae allergen extract was manufactured and characterized compared to D.farinae extract used for human immunotherapy. The protein profile was analysed by SDS-PAGE and size exclusion chromatography and Der f 15 and Der f 18 allergens quantified by mass spectrometry. The allergenic profile was studied by immunoblot and the biological potency by enzyme-linked immunosorbent assay-inhibition assays. The extract's capacity to induce cytokine production [interleukin (IL)-10, interferon (IFN)-Ɣ] by peripheral blood mononuclear cells also was evaluated. The veterinary extract showed a higher content of high molecular weight proteins, preferentially recognized by atopic dog sera. The fold-increases in Der f 15 and Der f 18 with respect to the human extract were 2.07±0.32 and 1.63±0.15, respectively. The veterinary extract showed higher biological potency (0.062 versus 0.132µg required for 50% inhibition of dogs sera) compared to the human extract and induced significantly higher levels of IL-10 (1,780pg/mL) and IFN-Ɣ (50.4pg/mL) with respect to the negative control. A veterinary D.farinae extract with a higher content of dog major allergens was developed and in vitro efficacy demonstrated by immunological parameters.

Intradermal Phleum pratense allergoid immunotherapy. Double-blind, randomized, placebo-controlled trial.

BackgroundIn allergology, the intradermal approach is generally used to establish an aetiological diagnosis, with limited experience in specific allergen immunotherapy.ObjectiveTo evaluate the efficacy and safety of immunotherapy with an allergen extract of glutaraldehyde‐polymerized Phleum pratense, administered intradermally, in patients with rhinoconjunctivitis sensitized to grass pollen.MethodsMulticentre, randomized, double‐blind, placebo‐controlled clinical trial in patients from 12 to 65 years of age with rhinitis or rhinoconjunctivitis, with or without asthma, due to grass pollen allergy. Patients were divided into three groups and received a total of six doses in a weekly interval, of either placebo; 0.03 or 0.06 μg of protein per dose of P pratense allergoid. The primary objective was to evaluate the combined symptoms and medication consumption score (CSMS). The secondary objectives were symptoms and medication, tolerance to the conjunctival provocation test, specific IgE and IgG4 antibodies and the safety profile according to the WAO scale.ResultsThe dose of 0.06 μg of protein proved to be effective versus the placebo by significantly reducing CSMS and increasing tolerance to the allergenic extract in the conjunctival provocation test, after the first pollen season. This group showed a significant reduction in specific IgE after the second pollen season relative to the baseline. There were no variations in IgG4 levels. Only one grade 2 systemic reaction was recorded.Conclusion & Clinical RelevanceIntradermal immunotherapy with P pratense allergoid has been shown to be effective and safe, reducing CSMS, increasing tolerance to the conjunctival provocation test and reducing IgE levels.

Identification of peroxidase-1 and beta-glucosidase as cross-reactive wheat allergens in grass pollen-related wheat allergy

BackgroundSome patients with wheat-dependent exercise-induced anaphylaxis (WDEIA) or wheat allergy showed negative ω-5 gliadin-specific IgE test and high level of grass pollen-specific IgE. It was presumed that these patients developed allergic reaction upon cross-reaction of their IgE antibodies raised against grass pollen allergens to wheat allergens. This study aimed to clarify clinical characteristics and wheat allergens of this phenotype of WDEIA/wheat allergy, which were tentatively diagnosed as grass pollen-related wheat allergy (GPWA). MethodsA total of six patients with GPWA were enrolled, and controls were 17 patients with grass pollen allergy but no episode of wheat allergy, and 29 patients with other wheat allergies: 18 with conventional WDEIA and 11 with hydrolyzed wheat protein allergy. Sensitization to wheat proteins was determined by basophil activation test (BAT). IgE-binding proteins in wheat flour were identified by immunoblotting followed by mass spectrometry. Wheat allergen-specific IgE tests were established by CAP-FEIA system. ResultsAll the six patients with GPWA were sensitized to water-soluble wheat proteins in BAT and IgE-immunoblotting, and peroxidase-1 (35 kDa) and beta-glucosidase (60 kDa) were identified as specific IgE-binding wheat proteins. The binding of patient IgE to these proteins was inhibited by pre-incubation of patient sera with grass pollen. The peroxidase-1- and beta-glucosidase-specific IgE tests identified three and four of six patients with GPWA, respectively, but only two of 29 controls, indicating high specificity of these tests. ConclusionsPeroxidase-1 and beta-glucosidase are specific wheat allergens for GPWA among grass pollen allergy and other types of wheat-induced food allergies.

Age-Related Features of Mast Cell Reactivity in Allergies

Introduction: During last few years, a novel scientific sphere has developed and is successfully growing,associated with the study of age-related changes in immune and allergic reactions at the cellular level.Although there is a fact that mast cells are the subject of many researches, many aspects of their physiologyand pathology remain unsolved. Moreover, clarification in the age-related features of mast cell reactivitymakes a great contribution to the expansion of our view of point on the characteristics of the clinic, etiologyand pathogenesis of allergies in ontogenesis.Materials and Method: We used 443 guinea pigs of both sexes of different ages, previously experienced 10-14 day-quarantine control under conditions of vivariums. Animals were constantly monitored, body weightwas periodically determined, and rectal temperature was measured. Sensitization and anaphylactic reactionswere reproduced by conventional method. Normal horse serum was used as an allergen. The resolving doseof a specific allergen was administered once intravenously or intraperitoneally 14-16 days after the startof the first sensitizing dose of the allergen. Collected digital data processed on electronic microcalculatorRokwell international Model 44 (USA).Results: With age, the rate of filling mast cells with granules increases. In guinea pigs of an older age, ascompared to newborns, the rates of filling mast cells with granules are 1.3-2.2 times greater (p &lt;0.05), whichis consistent with the literature. Spontaneous mast cell degranulation was observed in intact animals. Theirfrequency ranged from 5.4 to 8.6% and, in principle, did not depend on age. A comparative analysis of thefrequency of degranulation, depending on age, showed that the frequency of degranulation in sensitizednewborns is slightly lower than in older animals. However, with age in sensitized guinea pigs, the frequencyof degranulated mast cell forms increased and the mast cell reactivity in one month aged pigs becameapproximately the same as in mature animals.Conclusion: In general, the functional activity of mast cells increases with age, and by the age of one monthreaches the level of functional activity. In the development of specific therapy, a decrease in the titer ofhomocytotropic antibodies and the percentage of mast cell degranulation is vital.

Comparison between Specific Immunoglobulin E and Skin Prick Test for Diagnosis of Allergic Patients

Background: Skin prick test (SPT) has been identified as the gold standard method to diagnose IgE mediated hypersensitivities; it is accurate, easy and cheap. However, SPT has some important limitations, so in vitro serum specific serum IgE (sSIgE) detection can be a good alternative. The diagnostic yield of sSIgE testing usually depends on the specific allergen. Objective: This study compares between SPT and sSIgE for diagnosis of allergy. Methodology: 61 allergic patients enrolled from Zagazig University Allergy and Immunology Unit, tested by SPT for the common allergens. Serum total IgE and specific IgE levels were measured and compared to SPT results. Results: The over- all sensitivities of sSIgE were excellent (75-100%) for most of allergens tested. PPV was excellent with some allergens (pollens, cockroaches, mites) and poor with others (cat hair). Sensitivity of mites sSIgE was excellent with PPV approaching 90%, specificiy was only 13%. However, the NPV was 100%. Significant level of agreement and correlation between the results of SPT and sSIgE for cockroaches and molds was reported. Positive correlation between the total levels of serum IgE and the diameter of wheal and flare of the SPT for mites, pollens and cockroaches was found. Conclusion: The sensitivities of sSIgE were excellent for most of allergens tested. Specificity of sSIgE varies between individual allergens. Serum specific IgE testing may be a good alternative to skin prick test if the latter could not be carried out.

Biomarkers for diagnosis and prediction of therapy responses in allergic diseases and asthma.

Modern health care requires a proactive and individualized response to diseases, combining precision diagnosis and personalized treatment. Accordingly, the approach to patients with allergic diseases encompasses novel developments in the area of personalized medicine, disease phenotyping and endotyping, and the development and application of reliable biomarkers. A detailed clinical history and physical examination followed by the detection of IgE immunoreactivity against specific allergens still represents the state of the art. However, nowadays, further emphasis focuses on the optimization of diagnostic and therapeutic standards and a large number of studies have been investigating the biomarkers of allergic diseases, including asthma, atopic dermatitis, allergic rhinitis, food allergy, urticaria and anaphylaxis. Various biomarkers have been developed by omics technologies, some of which lead to a better classification of distinct phenotypes or endotypes. The introduction of biologicals to clinical practice increases the need for biomarkers for patient selection, prediction of outcomes and monitoring, to allow for an adequate choice of the duration of these costly and long‐lasting therapies. Escalating healthcare costs together with questions about the efficacy of the current management of allergic diseases require further development of a biomarker‐driven approach. Here, we review biomarkers in diagnosis and treatment of asthma, atopic dermatitis, allergic rhinitis, viral infections, chronic rhinosinusitis, food allergy, drug hypersensitivity and allergen immunotherapy with a special emphasis on specific IgE, the microbiome and the epithelial barrier. In addition, EAACI guidelines on biologicals are discussed within the perspective of biomarkers.

IgE Epitope Profiling for Allergy Diagnosis and Therapy - Parallel Analysis of a Multitude of Potential Linear Epitopes Using a High Throughput Screening Platform.

Immunoglobulin E (IgE) is pivotal for manifestation and persistence of most immediate-type allergies and some asthma phenotypes. Consequently, IgE represents a crucial target for both, diagnostic purposes as well as therapeutic approaches. In fact, allergen-specific immunotherapy – aiming to re-route an IgE-based inflammatory response into an innocuous immune reaction against the allergen – is the only curative approach for IgE-mediated allergic diseases known so far. However, this requires the cognate allergen to be known. Unfortunately, even in well-characterized allergics or asthmatics, often just a small fraction of total IgE can be assigned to specific target allergens. To overcome this knowledge gap, we have devised an analytical platform for unbiased IgE target epitope detection. The system relies on chemically produced random peptide libraries immobilized on polystyrene beads (“one-bead-one-compound (OBOC) libraries”) capable to present millions of different peptide motifs simultaneously to immunoglobulins from biological samples. Beads binding IgE are highlighted with a fluorophore-labeled anti-IgE antibody allowing fluorescence-based detection and isolation of positives, which then can be characterized by peptide sequencing. Setting-up this platform required an elaborate optimization process including proper choice of background suppressants, secondary antibody and fluorophore label as well as incubation conditions. For optimal performance our procedure involves a sophisticated pre-adsorption step to eliminate beads that react nonspecifically with anti-IgE secondary antibodies. This step turned out to be important for minimizing detection of “false positive” motifs that otherwise would erroneously be classified as IgE epitopes. In validation studies we were able to retrieve artificial test-peptide beads spiked into our library by using IgE directed against those test-peptides at physiological concentrations (≤20 IU/ml of specific IgE), and disease-relevant bead-bound epitopes of the major peanut allergen Ara h 2 by screening with sera from peanut allergics. Thus, we established a platform with which one can find and validate new immunoglobulin targets using patient material which displays a largely unknown immunoglobulin repertoire.

Air pollution and IgE sensitization in 4 European birth cohorts—the MeDALL project

Whether long-term exposure air to pollution has effects on allergic sensitization is controversial. Our aim was to investigate associations of air pollution exposure at birth and at the time of later biosampling with IgE sensitization against common food and inhalant allergens, or specific allergen molecules, in children aged up to 16 years. A total of 6163 children from 4 European birth cohorts participating in the Mechanisms of the Development of ALLergy [MeDALL] consortium were included in this meta-analysis of the following studies: Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) (Sweden), Influences of Lifestyle-Related Factors on the Human Immune System and Development of Allergies in Childhood (LISA)/German Infant Study on the Influence of Nutrition Intervention PLUS Environmental and Genetic Influences on Allergy Development (GINIplus) (Germany), and Prevention and Incidence of Asthma and Mite Allergy (PIAMA) (The Netherlands). The following indicators were modeled by land use regression: individual residential outdoor levels of particulate matter with aerodynamic diameters less than 2.5 μm, less than 10 μm, and between 2.5 and 10 μm; PM2.5 absorbance (a measurement of the blackness of PM2.5 filters); and nitrogen oxides levels. Blood samples drawn at ages 4 to 6 (n= 5989), 8 to 10 (n= 6603), and 15 to 16 (n= 5825) years were analyzed for IgE sensitization to allergen extracts by ImmunoCAP. Additionally, IgE against 132 allergen molecules was measured by using the MedALL microarray chip (n= 1021). Air pollution was not consistently associated with IgE sensitization to any common allergen extract up to age 16 years. However, allergen-specific analyses suggested increased risks of sensitization to birch (odds ratio [OR]= 1.12 [95% CI= 1.01-1.25] per 10-μg/m3 increase in NO2 exposure). In a subpopulation with microarray data, IgE to the major timothy grass allergen Phleum pratense 1 (Phl p 1) and the cat allergen Felis domesticus 1 (Fel d 1) greater than 3.5 Immuno Solid-phase Allergen Chip standardized units for detection of IgE antibodies were related to PM2.5 exposure at birth (OR= 3.33 [95% CI= 1.40-7.94] and OR= 4.98 [95% CI= 1.59-15.60], respectively, per 5-μg/m3 increase in exposure). Air pollution exposure does not seem to increase the overall risk of allergic sensitization; however, sensitization to birch as well as grass pollen Phl p 1 and cat Fel d 1 allergen molecules may be related to specific pollutants.