Allergen Sources Research Articles

Molecular allergy diagnosis enabling personalized medicine.

Allergic patients are characterized by complex and patient-specific IgE sensitization profiles to various allergens, which are accompanied by different phenotypes of allergic disease. Molecular allergy (MA) diagnosis establishes the patient's IgE reactivity profile at a molecular allergen level and has moved allergology into the "Precision Medicine" era. Molecular allergology started in the late 1980s with the isolation of the first allergen-encoding DNA sequences. Already in 2002, the first allergen microarrays were developed for the assessment of complex IgE sensitization patterns. Recombinant allergens are used for a precise definition of personal IgE reactivity profiles, identification of genuine IgE sensitization to allergen sources for refined prescription of allergen-specific immunotherapy and allergen avoidance diagnosis of co- versus cross-sensitization, epidemiological studies and prediction of symptoms, phenotypes, and development allergic disease. For example, molecular IgE sensitization patterns associated with more severe respiratory allergies, severe food allergy and allergy to honeybee or vespids are already established. The implementation of MA diagnosis into daily clinical practice requires continuous medical education, training of doctors in MA diagnosis and may be facilitated by clinical decision support systems such as diagnostic algorithms which may take advantage of artificial intelligence (AI).

Molecular Profiles of Sensitization to Non-Specific Lipid Transfer Proteins in Lithuania: Single Center Experience.

Non-specific Lipid Transfer proteins (nsLTPs) are relevant allergens of several pollens and plant foods. Sensitization to nsLTPs is not typical in our region. Still, it has become an increasingly common cause of IgE-mediated food allergies and food-induced anaphylaxis in Northern Europe in recent decades. No in-depth studies describe the prevalence of sensitization of molecular components to nsLTPs in Lithuania. This study aimed to determine the sensitization profile of atopic patients at the Immunology and Allergy Department of Kauno Klinikos to the components of nsLTPs, using molecular allergen component analysis. Sixty Lithuanian adults with symptoms of allergic rhinitis and/or allergic asthma and/or food allergies were included into the study. Specific immunoglobulin E (IgE) levels were measured using two in vitro techniques: allergen extract and molecular component analysis. Results showed that 25% of subjects were sensitized to nsLTP-containing allergen sources, mostly to Zea m 14, Mal d 3, Vit v 1, and Art v 3. The median amount of total IgE was higher in nsLTP-sensitized patients than in nsLTP-nonsensitized patients. Based on Cohen's Kappa and McNemar tests, the results of allergen extract and component analysis tests do not always agree, especially when we determine the sensitization to allergen sources containing nsLTPs. Molecular allergen component analysis could be the first choice in determining detailed sensitization to nsLTPs in patients who experienced anaphylaxis of unknown origin.

Safety evaluation of the food enzyme containing endo-polygalacturonase and β-glucosidase from the non-genetically modified Aspergillus tubingensis strain ARO.

The food enzyme containing endo-polygalacturonase and β-glucosidase (EC 3.2.1.15 and EC 3.2.1.21) is produced with the non-genetically modified Aspergillus tubingensis strain ARO by DSM Food Specialties B.V. The food enzyme was free from viable cells of the production organism. It is intended to be used in five food manufacturing processes. Dietary exposure was estimated to be up to 0.609 mg total organic solids (TOS)/kg body weight per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 2217 mg TOS/kg bw per day, the highest dose tested, resulting in a margin of exposure of at least 3640. A search for the homology of the amino acid sequence of the food enzymes to known allergens was made and four matches with food allergens and 22 matches with respiratory allergens were found. Known sources of food allergens were used in the food enzyme manufacturing process. The Panel considered that the risk of allergic reactions upon dietary exposure cannot be excluded. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.

Safety evaluation of the food enzyme fructan β-fructosidase from the genetically modified Trichoderma reesei strain AR-577.

The food enzyme fructan β-fructosidase (β-d-fructan fructohydrolase; EC 3.2.1.80) is produced with the genetically modified Trichoderma reesei strain AR-577 by AB Enzymes GmbH. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and its DNA. The food enzyme is intended to be used in the processing of cereals and other grains for the production of baked products and cereal-based products other than baked. Dietary exposure was estimated to be up to 0.181 mg total organic solids (TOS)/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 1000 mg TOS/kg bw per day, the highest dose tested, which when compared with the estimated dietary exposure, results in a margin of exposure of at least 5495. A search for homology of the amino acid sequence of the food enzyme to known allergens was made and no match was found. A known source of food allergens was used in the food enzyme manufacturing process. The Panel considered that the risk of allergic reactions upon dietary exposure cannot be excluded but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.

Safety evaluation of the food enzyme protein‐glutamine γ‐glutamyltransferase from the non‐genetically modified Streptomyces mobaraensis strain AE‐BTG

Abstract The food enzyme protein‐glutamine γ‐glutamyltransferase (protein‐glutamine: amine γ‐glutamyltransferase; EC 2.3.2.13) is produced with the non‐genetically modified S. mobaraensis strain AE‐BTG by AJINOMOTO EUROPE SAS. The food enzyme was free from viable cells of the production organism. It is intended to be used in nine food manufacturing processes. Dietary exposure to the food enzyme–total organic solids (TOS) was estimated to be up to 0.398 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90‐day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 538 mg TOS/kg bw per day which when compared with the estimated dietary exposure, resulted in a margin of exposure of at least 1351. A search for homology of the amino acid sequence of the food enzyme to known allergens was made and no match was found. Known sources of food allergens were used in the food enzyme manufacturing process, and the Panel considered that the risk of allergic reactions upon dietary exposure to this food enzyme cannot be excluded. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.

Safety evaluation of the food enzyme endo-1,4-β-xylanase from the non-genetically modified Trichoderma citrinoviride strain HBI-TX01.

The food enzyme endo-1,4-β-xylanase (4-β-d-xylan xylanohydrolase; EC 3.2.1.8) is produced with Trichoderma citrinoviride strain HBI-TX01 by HBI Enzymes Inc. The food enzyme is free from viable cells of the production organism. It is intended to be used in four food manufacturing processes. Since residual amounts of food enzyme-total organic solids (TOS) are removed in two food manufacturing processes, dietary exposure was calculated only for the remaining two processes. It was estimated to be up to 1.488 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 1101 mg TOS/kg bw, the highest dose tested, which when compared with the estimated dietary exposure, resulted in a margin of exposure of at least 740. A search for homology of the amino acid sequence of the food enzyme to known allergens was made and no match was found. Known sources of food allergens were used in the manufacturing process. The Panel considered that the risk of allergic reactions upon dietary exposure to this food enzyme cannot be excluded, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.

Incorporating Aeroallergen Exposure Metrics into Clinical Asthma Care: A Pilot Study Using A Mixed-Methods Survey to Assess Aeroallergen Knowledge, Perceived Asthma Control, and Mitigation Strategies in Households of Children with Asthma.

Objective: Mitigation of household allergens is associated with the reduction of asthma exacerbations in those with allergic asthma and is recommended in recent asthma guidelines. However, we need to better understand patient knowledge of aeroallergens in their homes prior to integrating direct allergen measurement methods into standard asthma care. Methods: We conducted a mixed-methods sequential pilot study consisting of a survey and virtual interview with caregivers of children aged 3 to 15 with asthma diagnosis (any severity) about asthma control, household environment, mitigation knowledge and strategies, and knowledge of allergens and asthma. Results: A total of 21 participants responded and 13 completed the virtual interview. Less than half identified mice (43%), rats (29%), and cockroaches (43%) as sources of allergens on the online survey, and no individuals mentioned these in discussions. Only 23% were able to define the term "allergen," but 69% could list examples. There was a poor correlation between perceived asthma control (57% stated asthma control was good or excellent) compared to asthma that was classified as well controlled per Expert Panel Report 3 (EPR-3) guidelines (33% based on albuterol use and asthma symptoms). Finally, visual identification of mouse infestation was associated with active steps taken to mitigate mouse exposure (P = 0.007). Conclusion: Implementation of new Asthma Management Guidelines: Focused Updates 2020 by the National Institutes of Health will require additional aeroallergen education for individuals with asthma who do not recognize that cockroaches, rats, and mice can cause asthma symptoms, do not know the definition of an allergen, and do not correctly perceive asthma control status. Environmental assessment with education addressing these could hopefully decrease additional pharmaceutical needs.

Clinical diagnosis and management of wheat and buckwheat allergy: application and prospects of allergen component diagnostics

Wheat and buckwheat allergies are common food allergies that significantly impact patients' quality of life and health. Wheat allergy encompasses various forms, including wheat food allergy, exercise-induced allergic reactions (WDEIA), baker's occupational asthma/allergy, and contact urticaria. IgE-mediated allergic reactions involve sensitization to stable wheat allergens such as ω-5 gliadin and gluten. Although buckwheat allergy is less common, it is gaining attention in certain regions. Allergen component diagnostic technologies, by detecting specific allergen components [e.g., ω-5 gliadin, gliadins (α, β, γ), and Tri a 14], offer precise allergen source identification, aiding in the optimization of diagnosis and management processes. Oral challenge tests are considered the gold standard for diagnosing wheat allergy, and combining skin prick tests with specific IgE measurements can enhance diagnostic accuracy. While avoidance of allergens remains the primary management strategy, research into immunotherapy is ongoing. Future research should focus on a deeper understanding of the structural and immunological characteristics of wheat and buckwheat allergens to develop more accurate diagnostic tools and treatment methods, thereby improving allergy management and patient quality of life. This article provides a detailed interpretation of the Molecular Allergology User's Guide 2.0 (MAUG 2.0) published by the European Academy of Allergy and Clinical Immunology (EAACI) and recent research advances on wheat and buckwheat allergies, highlighting the crucial role of allergen component diagnostics in optimizing food allergy diagnosis and treatment processes, supporting clinicians in accurately identifying common allergens and their cross-reactivity, and formulating more personalized treatment plans for patients.

Cell wall nanoparticles from hyphae of Alternaria infectoria grown with caspofungin, nikkomycin, or pyroquilon trigger different activation profiles in macrophages.

Alternaria infectoria causes opportunistic human infections and is a source of allergens leading to respiratory allergies. In this work, we prepared cell wall nanoparticles (CWNPs) as a novel approach to study macrophage immunomodulation by fungal hyphal cell walls. A. infectoria was grown in the presence of caspofungin, an inhibitor of β(1,3)-glucan synthesis; nikkomycin Z, an inhibitor of chitin synthases; and pyroquilon, an inhibitor of dihydroxynaphthalene (DHN)-melanin synthesis. Distinct CWNPs were obtained from these cultures, referred to as casCWNPs, nkCWNPs, and pyrCWNPs, respectively. CWNPs are round-shaped particles with a diameter of 70-200 nm diameter particles that when added to macrophages are taken up by membrane ruffling. CWNPs with no DHN-melanin and more glucan (pyrCWNPs) caused early macrophage activation and lowest viability, with the cells exhibiting ultrastructural modifications such as higher vacuolization and formation of autophagy-like structures. CasCWNPs promoted the highest tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) increase, also resulting in the release of partially degraded chitin, an aspect never observed in macrophage-like cells and fungi. After 6 h of interaction with CWNPs, only half were viable, except with control CWNPs. Overall, this work indicates that compounds that modify the fungal cell wall led to CWNPs with new properties that may have implications for the effects of drugs during antifungal therapy. CWNPs provide a new tool to study the interaction of hyphal fungal cell wall components with phagocytic cells and enable to show how the modification of cell wall components in A. infectoria can modulate the response by macrophages.IMPORTANCEAlternaria species are ubiquitous environmental fungi to which the human host can continuously be exposed, through the inhalation of fungal spores but also of fragments of hyphae, from desegregated mycelia. These fungi are involved in hypersensitization and severe respiratory allergies, such as asthma, and can cause opportunistic infections in immunodepressed human host leading to severe disease. The first fungal structures to interact with the host cells are the cell wall components, and their modulation leads to differential immune responses. Here, we show that fungal cells grown with cell wall inhibitors led to cell wall nanoparticles with new properties in their interaction with macrophages. With this strategy, we overcame the limitation of in vitro assays interacting with filamentous fungi and showed that the absence of DNH-melanin leads to higher virulence, while caspofungin leads to cells walls that trigger higher hydrolysis of chitin and higher production of cytokines.

Safety evaluation of the food enzyme α-amylase from the non-genetically modified Bacillus amyloliquefaciens strain UN-01.

The food enzyme α-amylase (4-α-d-glucan glucanohydrolase; EC 3.2.1.1) is produced with the non-genetically modified microorganism Bacillus amyloliquefaciens strain UN-01 by Nagase (Europa) GmbH. The production strain qualified for the qualified presumption of safety approach and no issues of concern arose from the production process of the food enzyme, therefore, the Panel considered that toxicological studies were unnecessary. It is intended to be used in five food manufacturing processes. Since residual amounts of total organic solids (TOS) are removed during two processes, dietary exposure was calculated only for the remaining three food manufacturing processes. It was estimated to be up to 0.434 mg TOS/kg body weight per day in European populations. A search for homology of the amino acid sequence of the food enzyme to known allergens was made and one match with a respiratory allergen was found. Known sources of food allergens were used in the food enzyme manufacturing process. The Panel considered that the risk of allergic reactions upon dietary exposure to this food enzyme cannot be excluded. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.

Safety evaluation of the food enzyme α-amylase from the non-genetically modified Bacillus amyloliquefaciens strain AE-BAA.

The food enzyme α-amylase (4-α-d-glucan glucanohydrolase; EC 3.2.1.1) is produced with the non-genetically modified microorganism Bacillus amyloliquefaciens strain AE-BAA by Amano Enzyme Inc. The food enzyme is intended to be used in eight food manufacturing processes. Since residual amounts of food enzyme-total organic solids (TOS) are removed in two processes, dietary exposure was calculated only for the remaining six food manufacturing processes. It was estimated to be up to 0.842 mg TOS/kg body weight per day in European populations. The production strain of the food enzyme fulfils the requirements for the qualified presumption of safety (QPS) approach to safety assessment. Consequently, in the absence of other concerns, the Panel considered that toxicological studies were not needed for the safety assessment of this food enzyme. A search for the homology of the amino acid sequence of the food enzyme to known allergens was made and one match with a respiratory allergen was found. Known sources of food allergens were used in the manufacturing process, and the Panel considered that the risk of allergic reactions upon dietary exposure to this food enzyme cannot be excluded. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.

Safety evaluation of the food enzyme glucan-1,4-α-glucosidase from the non-genetically modified Aspergillus niger strain DP-Azh100.

The food enzyme glucan-1,4-α-glucosidase (4-α-d-glucan glucohydrolase; EC 3.2.1.3) is produced with the non-genetically modified Aspergillus niger strain DP-Azh100 by Genencor International B.V. It was considered free from viable cells of the production organism. The food enzyme is intended to be used in four food manufacturing processes. Since residual amounts of total organic solids (TOS) are removed in two processes, dietary exposure was calculated only for the two remaining processes. It was estimated to be up to 1.390 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level at the highest dose tested of 1000 mg TOS/kg bw per day, which when compared with the estimated dietary exposure, resulted in a margin of exposure of at least 719. A search for the homology of the amino acid sequence of the food enzyme to known allergens was made and one match to a respiratory allergen was found. Known sources of food allergens were used in the food enzyme manufacturing process. The Panel considered that the risk of allergic reactions upon dietary exposure to this food enzyme cannot be excluded, but the likelihood is low. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns, under the intended conditions of use.

Improved quality control of allergen products: Assessing the molecular allergen composition by mass spectrometry.

Natural allergen sources contain a variety of allergens, against which allergic subjects have developed individual sensitization profiles. Ideal allergen products for skin prick testing (SPT) and allergen immunotherapy (AIT) should contain the complete set of allergens of the respective allergen sources to cover all sensitization profiles. However, commercially available allergen products were shown to vary regarding their allergen composition. The qualitative allergen composition of different SPT and AIT products produced from pollen of grasses, birch, mugwort and from house dust mites was assessed by a consistent high-resolution liquid chromatography-coupled tandem mass spectrometry method (LC-MS/MS). All major, mid-tier and most minor allergens were detected in each of the investigated three batches of SPT and AIT products, demonstrating the completeness of the allergen composition and a high degree of batch-to-batch consistency. This is the first study using a single consistent high-resolution LC-MS/MS method to provide solid data on the qualitative allergen composition of SPT and AIT products manufactured from various common allergen sources. The applied method showed high reliability in qualitative batch-to-batch consistency testing and can be performed fast and with high throughput. High-resolution LC-MS/MS is applicable for process development and quality control to ensure market availability of allergen products corresponding to the composition of the respective natural allergen sources.

Characteristics of Fungal Monosensitization in Turkey

Study ObjectiveFungi are recognized as allergenic sources and may play a role in the development, persistency, and severity of allergic diseases. Alternaria, Cladosporium, Penicillium, and Aspergillus, which belong to the Phylum Ascomycota, are well-characterized four genera among fungi species. To our knowledge, there is not enough data about monosensitization to fungi. We aimed to investigate the characteristics of monosensitized patients to fungal allergens. Patients-MethodsSixty-seven adult patients, who had a positive skin prick test reaction with fungal allergen out of a total of 4200 SPT results performed between January 2015 and June 2022 in two tertiary centers were included in the study. The clinical data of the patients were obtained retrospectively from the hospital medical records. ResultsFifty-six (83.6%) patients were sensitized to one type of fungal allergen (Female/Male: 38/18) and eleven (16.4%) (Female/Male: 9/2) were sensitized to two types of fungi. Aspergillus was the most prevalent fungal allergen, followed by Cladosporium and Alternaria. Allergic rhinitis was the most common allergic disease. ConclusionMonosensitization to fungal allergens is rare. Monosensitization to at least one fungal allergen may lead to significant allergic diseases by potentially impacting the immune system.

Identification, Purification, and Characterization of Kunitz-Type Protease Inhibitors from White-Fleshed Dragon Fruit (Selenicereus undatus) and Red-Fleshed Dragon Fruit (Selenicereus costaricensis) Seeds as Novel Food Allergens.

There have been clinical reports of allergies to dragon fruits. However, little is known about the allergens that trigger these reactions. This study aimed to investigate novel allergens in dragon fruits. The peptide mass fingerprints of two purified natural allergens were identified by LC-MS/MS with chymotrypsin proteolysis. The complete amino acid sequences of the allergens were deduced from cDNA amplicon sequences. The coding sequences of two allergens were inserted in the expression vector pColdI, and recombinant allergens were produced in Escherichia coli. Circular dichroism was performed to analyze the secondary structures of natural and recombinant allergens. Our results identified two novel allergens as Kunitz-type protease inhibitors. Recombinant allergens exhibited well-folded structures, predominantly composed of β-sheets, similar to their natural counterparts. IgE reactivity analysis with sera from ten patients primarily sensitized to dragon fruit indicated that Kunitz-type protease inhibitors are major allergens in dragon fruits. These results improve our understanding of allergen sources and provide important insights into the allergenicity of proteins from different species.

Microarray-based evaluation of selected recombinant timothy grass allergens expressed in E. Coli and N. Benthamiana

BackgroundTimothy grass (Phleum pratense) is a significant source of allergens, and recombinant allergens are increasingly used for diagnostic purposes. However, the performance of different recombinant allergen production systems in diagnostic assays needs further investigation to optimize their use in clinical settings.ObjectiveThe main objective of this study was to analyze and compare the diagnostic performance of recombinant timothy grass allergens produced in E. coli and N. benthamiana using a custom-made microarray chip.MethodsRecombinant timothy grass allergens Phl p 1, Phl p 2, Phl p 5, Phl p 6, Phl p 11, and Phl p 12 were produced in E. coli and/or N. benthamiana. A total of 113 patient serum samples were tested to evaluate the diagnostic sensitivity, specificity, inter-assay variability, and correlation of allergen-specific IgE detection compared to commercial multiplex tests (ALEX and ISAC). Additionally, the prevalence of sIgE to these allergens was assessed.ResultsPhl p 1, Phl p 2, Phl p 5, Phl p 6 and Phl p 11 showed high or very high positive correlation in immunoreactivity with other commercial multiplex tests. Notably, Phl p 11 fused with maltose-binding protein (MBP) demonstrated high diagnostic specificity and sensitivity, with a 0.3 arbitrary cut-off value. However, a high intra-assay variation was observed. The study also assessed specific IgE prevalence to timothy grass allergens within the tested patient cohort.ConclusionsRecombinant allergens from both E. coli and N. benthamiana demonstrated strong diagnostic potential on the microarray platform, with Phl p 11 (MBP-fused) showing particularly high performance. High intra-assay variation highlights the need for further optimization in allergen formulation and microarray storage conditions. These results highlight the potential of recombinant allergens for diagnostic applications, despite challenges with allergen stability in microarray formats. Specific IgE prevalence to timothy allergens revealed a sensitization profile consistent with findings from multiple studies.Graphical

B-060 Prevalence of CCD and profilins antibodies in a seasonal allergy study

Abstract Background Allergen sources are complex and heterogeneous mixtures of proteins, which may contain from innocuous IgE-binding structures such as CCDs (cross-reactive carbohydrate determinants), which are not associated with symptoms, to a panallergen such as profilin, which is associated with multiple sensitizations to pollen and pollen-food-latex syndromes. CCDs are present in many plant and animal allergens and cause strong cross-reactivity due to the high similarity of their structure. They complicate the interpretation of positive in vitro diagnostic results because they do not associate symptomatology and, thats why, the determination of specific IgE antibodies against CCDs can provide useful information when positive IgE results are not consistent with the clinical picture. Profilins are ubiquitous proteins present in all eukaryotic cells and identified as allergens in pollen, latex and plant foods. The highly conserved structure explains the cross-reactivity of IgE antibodies against plant profilins and their designation as panallergens. As a panallergen, profilin is associated with multiple pollen sensitization and pollen-food-latex syndromes that the allergist must be aware of for accurate diagnosis and successful treatment of allergic diseases. We intend to evaluate the prevalence of these two markers with a new diagnostic tool, since profilins and CCDs are the substances most likely to cause in vitro cross-reactivity. Methods In our study 8,242 adults who presented rhinoconjunctivitis and visited their primary care center were included. The samples were analyzed in serum samples which were routinely processed in our laboratory with the EUROLINE Mediterranean Inhalation 2 (IgE) assay from Euroimmun® from February to July 2023, according to the manufacturer’s protocols. Patients with specific IgE levels ≥ 0.35 kU/L were identified as sensitized to allergen. Results A total of 8,242 patients were enrolled in this study, 5,173 women and 3,069 men, ranging in age from 15 to 65 years. Of these, 279 patients (3.39%) had antibodies against CCD, 570 (6.92%) antibodies against profilins and 183 (2.22%) had both. A higher prevalence of these antibodies was observed in men (CCD, n = 168, 5.47%; Profilins, n = 308, 10.04%) than in women (CCD, n = 111, 2.15%; Profilins, n = 262, 5.06%). Both markers were more frequently found in the presence of specific IgE antibodies to grass and weed pollens. Conclusions The possibility of detecting the presence of IgE antibodies against CCD and panallergenic profilins is useful to detect cross-reactivity in vitro, which could explain the differences found between laboratory results and patients' symptoms, helping the allergist to make a diagnosis with greater certainty and accuracy.

Role of specific immunoglobulin-E in chronic rhinosinusitis: Its clinical relevance according to nasal challenge test

BackgroundGuidelines for chronic rhinosinusitis (CRS) propose total IgE and eosinophils as important biomarkers to identify type-2 inflammation. Despite the fact that specific IgE (sIgE) have been identified as a clinical predictor in some type-2 diseases for different clinical outcomes, its role in CRS has yet to be explored in detail. ObjetiveTo describe systemic and local sIgE in CRS and explore its possible association with clinical outcomes using nasal challenge tests (NCT). MethodsIn CRS patients, we measure total IgE, serum sIgE (SsIgE) and nasosinusal sIgE (NsIgE) against 9 allergenic sources; Der p, Der f, Blo t, Can f, Fel d, Per a, grasses, Staphylococcus enterotoxin A, and B. NCT was done using the allergen with the higher sIgE prevalence (Der p). ResultsA total of 174 patients were included. Prevalence of SsIgE was 52.8% and NsIgE 46.5%; Der p was the principal allergen for SsIgE and NsIgE. The presence of nasal polyps, asthma comorbidity, NSAID hypersensitivity, and hyposmia, were significantly associated with the presence of SsIgE and NsIgE but not with total IgE. NCT-Der p was performed in 73 CRS patients, being positive in 33 (45.2%). SsIgE have the best diagnostic accuracy (79.4%) to predict NCT results (NsIgE 67.5% total IgE 52%). ConclusionSpecific IgE is a better biomarker in CRS than total IgE. Patients with clinically relevant SsIgE have a pheno-endotype associated with different clinical outcomes. Considering the clinical relevance of SsIgE demonstrated by NCT, interventions like allergen immunotherapy in CRS must be study.

In silico analysis of molecular mimicry between human aquaporin 3, Aspergillus fumigatus aquaporin and aquaporins from allergic sources.

Atopic dermatitis (AD) is a chronic inflammatory skin condition that has a significant impact on quality of life. The immune response and allergy symptoms in AD are triggered by the recognition of specific allergens by IgE antibodies. Cross-reactivity can lead to auto-IgE responses, potentially worsening AD symptoms. Our research aimed to enhance our understanding of allergenic sources, including A. fumigatus, and their role in AD. We focused on molecular mimicry between human AQP3 and A. fumigatus aquaporin. In our in-silico analysis, we compared the amino acid sequences of human aquaporin 3 (AQP3) and A. fumigatus aquaporin with 25 aquaporins from various allergenic sources, sourced from the UniProt and NCBI databases. Phylogenetic relationship analysis and homology-based modeling were conducted. We identified conserved antigenic regions located within the 3D structures. The global identity levels among the studied aquaporins averaged 32.6%. One antigenic site exhibited a remarkable local region, with a conserved identity of 71.4%. We categorized the aquaporins into five monophyletic clades (A-E), with group B showing the highest identity (95%), including six mammalian aquaporins, including AQP3. When comparing A. fumigatus aquaporins, the highest identity was observed with Malassezia sympodialis at 35%. Both human and A. fumigatus aquaporins have three linear and three discontinuous epitopes. We identified potential linear and conformational epitopes of AQP3, indicating a possible molecular mimicry between humans and A. fumigatus aquaporins. This suggests autoreactivity and potential cross-reactivity, although further validation using in vitro and in vivo experiments is required.

Changes in Prevalence of IgE Sensitization and Allergenic Exposition over a 10-Year Period in a Tropical Region

Introduction: Multiple antigen environmental sources have been identified as possible causes of allergies, but few studies have evaluated changes in the sensitization profiles over time. The aim of this study was to evaluate the changes in IgE sensitization and exposure to dust mites, cats, dogs, and cockroaches over a 10-year period. Methods: During a period of 10 years among patients with asthma, rhinitis and/or atopic dermatitis, we evaluated the annual frequency of atopy to Dermatophagoides farinae, Dermatophagoides pteronyssinus, Blomia tropicalis, Canis familiaris, Felis domesticus and cockroaches (Periplaneta americana and Blatella germanica). Exposure to sources was also assessed using questionnaires (Pets) or direct counts (House dust mites and cockroaches). The association between some risk factors and the prevalence of atopy was explored. Results: A total of 6,000 records were included. Among the patients, 82% had IgE sensitization to at least one of the six allergenic sources. Sensitization to Dermatophagoides spp. was the most frequent (>78%). Exposure and sensitization in the first decade of life to Dermatophagoides spp. seem to determine the molecular spreading to other allergenic sources. Exposure to Blomia tropical increases significantly over time (year 2015; 38% vs. year 2022; 51%, p 0.03). Exposure to dogs was higher than with cats but association between atopy and exposure was stronger with cats (OR 27.4, 95% CI: 22.3–33.6, p < 0.01). Conclusion: Exposure and sensitization in the first decade of life to Dermatophagoides spp. determine the molecular spreading of IgE antibodies to other allergenic sources. Household exposure to dogs and cats seems to be important for the subsequent development of atopy. Sensitization to B. tropicalis and cockroach appears to be mostly from cross-reactivity rather than direct exposure.