Routinely Used and Emerging Diagnostic and Immunotherapeutic Approaches for Wheat Allergy.

Wheat, a component of the staple diet globally, is a common food allergen in children. The symptoms of wheat allergy (WA) range from skin rash to shortness of breath, significantly impairing quality of life. Following initial clinical suspicion, individuals may undergo routinely used allergy tests such as a wheat allergen-specific skin prick test (SPT), a blood test for specific immunoglobulin E (sIgE) levels, or oral food challenge. Conventional management of WA lies in wheat avoidance, yet accidental consumption may be inevitable owing to the ubiquity of wheat in various food products. This article aims to provide an overview of the immunologic pathway of WA, followed by its emerging diagnostic methods, namely alcohol-soluble SPT extracts, component-resolved diagnosis, and the basophil activation test (BAT). The mechanisms underlying wheat allergen-specific oral immunotherapy (OIT) as well as a summary of the efficacy, tolerability, and safety of related clinical trials will then be discussed.

Food-Pollen Cross-Reactivity and its Molecular Diagnosis in China.

PURPOSE OF REVIEW: Plant-derived foods are one of the most common causative sources of food allergy in China, with a significant relationship to pollinosis. This review aims to provide a comprehensive overview of this food-pollen allergy syndrome and its molecular allergen diagnosis to better understand the cross-reactive basis. RECENT FINDINGS: Food-pollen cross-reactivity has been mainly reported in Northern China, Artemisia pollen is the major related inhalant source, followed by tree pollen (Betula), while grass pollen plays a minor role. Pollen allergy is relatively low in Southern China, with allergies to grass pollen being more important than weed and tree pollens. Rosaceae fruits and legume seeds stand out as major related allergenic foods. Non-specific lipid transfer protein (nsLTP) has been found to be the most clinically relevant cross-reacting allergenic component, able to induce severe reactions. PR-10, profilin, defensin, chitinase, and gibberellin-regulated proteins are other important cross-reactive allergen molecules. Artemisia pollen can induce allergenic cross-reactions with a wide range of plant-derived foods in China, and spring tree pollens (Betula) are also important. nsLTP found in both pollen and plant-derived food is considered the most significant allergen in food pollen cross-reactivity. Component-resolved diagnosis with potential allergenic proteins is recommended to improve diagnostic accuracy and predict the potential risk of causing allergic symptoms.

New light on an old syndrome: Role of Api g 7 in mugwort pollen-related celery allergy.

BACKGROUND: Celery root is known to cause severe allergic reactions in patients sensitized to mugwort pollen. OBJECTIVE: We studied clinically well-characterized patients with celery allergy by IgE testing with a comprehensive panel of celery allergens to disentangle the molecular basis of what is known as the celery-mugwort syndrome. METHODS: Patients with suspected food allergy to celery underwent a standardized interview. Main inclusion criteria were a positive food challenge with celery or an unambiguous case history of severe anaphylaxis. IgE to celery allergens (rApi g 1.01, rApi g 1.02, rApi g 2, rApi g 4, nApi g 5, rApi g 6, rApi g 7) and to mugwort allergens (rArt v 1, rArt v 3, rArt v 4) were determined. IgE levels ≥0.35 kUA/L were regarded positive. RESULTS: Seventy-nine patients with allergy to celery were included. Thirty patients had mild oral or rhinoconjunctival symptoms, and 49 had systemic reactions. Sixty-eight percent had IgE to celery extract, 80% to birch pollen, and 77% to mugwort pollen. A combination of Api g 1.01, 1.02, 4, 5, and 7 increased the diagnostic sensitivity for celery allergy to 92%. The lipid transfer proteins Api g 2 and Api g 6 were not relevant in our celery-allergic population. IgE to Api g 7, detected in 52% of patients, correlated closely (r = 0.86) to Art v 1 from mugwort pollen. Eleven of 12 patients with monosensitization to Api g 7 were IgE negative to celery extract. The odds ratio for developing a severe anaphylactic reaction rather than only mild oral symptoms was about 6 times greater (odds ratio, 5.87; 95% confidence interval, 1.08-32.0; P = .0410) for Api g 7-sensitized versus -nonsensitized subjects. CONCLUSION: There is an urgent need for routine diagnostic tests to assess sensitization to Api g 7, not only to increase test sensitivity but also to identify patients at risk of a severe allergic reaction to celery.

Expression, purification, and activity of novel allergen Tyr p 31 from Tyrophagus putrescentiae.

Allergen component products, such as recombinant proteins and epitope peptides of allergic components, are used as an adjunct to allergen-specific immunotherapy. We characterized a novel allergen, Tyr p 31, from Tyrophagus putrescentiae, a common allergenic mite. T. putrescentiae total RNA was amplified to Tyr p 31-encoding cDNA, which was inserted into pET28a(+). pET28a(+)-Tyr p 31 was then transformed into Rosetta 2 (DE3) pLysS cells and expressed under isopropyl ß-D-thiogalactoside induction. Next, we visualized Tyr p 31 through sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting based on its theoretical molecular weight. Recombinant Tyr p 31 (rTyr p 31) was purified, and its secondary structure was noted to comprise α-helices, antiparallel coils, ß-turns, parallel coils, and random coils. Our enzyme-linked immunosorbent assay and Western blotting results for T. putrescentiae-positive sera from children with allergic disorders demonstrated rTyr p 31-specific IgE-positivity rates of 72.41 % and 85.7 %, respectively. In BEAS-2B cells, rTyr p 31 increased IL-6 and IL-8 expression; furthermore, BEAS-2B cells treated with 30 µg/mL rTyr p 31 demonstrated 100 upregulated and 12 downregulated genes. In summary, we identified Tyr p 31, a novel T. putrescentiae allergen component, and noted rTyr p 31 to have a high IgE-binding rate and strong immunogenicity.

AIT 2023: Current innovation and future outlook.

Although used for over 100 years, allergen immunotherapy (AIT) is still an indispensable tool in modern allergy managemen20t due to its potential to cure allergic diseases. Its current rapid development through the application of personalized and precision medicine approaches is strongly supported by advances in mHealth, component-resolved diagnosis (CRD)-based diagnostics, validation of novel biomarkers, advanced data management, and development of novel preparations. This review summarizes the key advances in the field and shows the perspectives for further development of next-generation AIT treatments.

Component-resolved diagnosis in childhood and prediction of asthma in early adolescence: A birth cohort study.

INTRODUCTION: Component-resolved diagnosis (CRD) has been decisive in exploring the mechanisms of IgE sensitization, but the predictive ability to detect asthma has not been addressed. We aim to develop and evaluate the performance of a personalized predictive algorithm for asthma that integrates information on allergic sensitization using CRD. METHODS: One thousand one hundred one twenty-five children from the Generation XXI birth cohort were randomly selected to perform a screening test for allergic sensitization and a subsample was characterized using CRD against 112 allergen components. Allergen components were analyzed using volcano plots and partial least squares (PLS) analysis. Logistic regression was performed to assess the associations between the obtained latent components (LC) and allergic outcomes (asthma, rhinitis, eczema) including other potential predictors used in previous asthma risk scores. The accuracy of the model in predicting asthma was assessed using Receiver Operating Characteristic (ROC) curve statistics. RESULTS: In the PLS, the first LC was positively associated with asthma, rhinitis, and eczema. This LC was mainly driven by positive weights for Der p 1/2/23, Der f 1/2, and Fel d 1. The main components in the second LC were pollen and food allergens. History of early wheezing and parental allergy were included in the predictive model and the area under the curve improved to 0.82. CONCLUSIONS: This is the first approach to improve the clinical applicability of CRD by combining CRD and clinical data to predict asthma at 13 years. Sensitization to distinct allergen molecules seems relevant to improve the accuracy of asthma prediction models.

Allergy to fungi: Advances in the understanding of fungal allergens.

Allergic diseases are a major health problem due to their increasing incidence and high prevalence worldwide. Asthma has several aetiologies, and allergy plays an important role in its development in approximately 60% of adults and 80% of children and adolescents. Although the link between aeroallergen sensitization and asthma exacerbations has been long recognized, the investigations of the triggering allergens may be superficial in many asthma cases. The main allergenic sources related to asthma, and other allergic diseases, are pollens, mites, fungi, and animal epithelia. Fungi are considered the third most frequent cause of respiratory pathologies. Asthma caused by several fungi species may have a bad prognosis in some cases due to its severity and difficulty in avoidance methods. Despite the recognised relevance of fungi in respiratory allergies, the knowledge about fungal allergens seems to be scarce, with few descriptions of new allergens, compared to other allergenic sources. The study of major, minor, and cross-reactive fungal allergens, and their relevance in the allergic disease, might be crucial, not only to accurately diagnose these allergies, but also to predict exacerbations and responses to therapies, as well as for the development of personalized treatment plans in a fast-changing climate scenario.

Recurrent Anaphylaxis with Watermelon and Pumpkin Seeds in a Boy Tolerant to Their Pulps.

Background: Seeds are widely consumed as a traditional snack and have rich contents beneficial to health. With an increase in consumption rates, allergic reactions occur more frequently. We focus on multiple seed consumption related to recurrent anaphylaxis in this case. Case Presentation: We evaluated an 11-year-old boy with recurrent anaphylaxis. According to his medical records, he had been hospitalized several times, diagnosed with anaphylaxis, and treated. The family noticed direct (eating) or indirect contact with pumpkin seeds. In addition, the family mentioned another anaphylactic episode after watermelon seed and poppy seed bread consumption. We conducted skin prick-to-prick tests, examined total immunoglobulin E levels, and prescribed the treatment with an adrenalin autoinjector and preventive dietary recommendations. Conclusion: Anaphylaxis, particularly recurrent ones, should be evaluated with detailed anamnesis and supported with laboratory tests. Although seeds are beneficial and highly nutritious, it is necessary to consider them a source of allergens.

IgE-Mediated Shellfish Allergy in Children.

Shellfish, including various species of mollusks (e.g., mussels, clams, and oysters) and crustaceans (e.g., shrimp, prawn, lobster, and crab), have been a keystone of healthy dietary recommendations due to their valuable protein content. In parallel with their consumption, allergic reactions related to shellfish may be increasing. Adverse reactions to shellfish are classified into different groups: (1) Immunological reactions, including IgE and non-IgE allergic reactions; (2) non-immunological reactions, including toxic reactions and food intolerance. The IgE-mediated reactions occur within about two hours after ingestion of the shellfish and range from urticaria, angioedema, nausea, and vomiting to respiratory signs and symptoms such as bronchospasm, laryngeal oedema, and anaphylaxis. The most common allergenic proteins involved in IgE-mediated allergic reactions to shellfish include tropomyosin, arginine kinase, myosin light chain, sarcoplasmic calcium-binding protein, troponin c, and triosephosphate isomerase. Over the past decades, the knowledge gained on the identification of the molecular features of different shellfish allergens improved the diagnosis and the potential design of allergen immunotherapy for shellfish allergy. Unfortunately, immunotherapeutic studies and some diagnostic tools are still restricted in a research context and need to be validated before being implemented into clinical practice. However, they seem promising for improving management strategies for shellfish allergy. In this review, epidemiology, pathogenesis, clinical features, diagnosis, and management of shellfish allergies in children are presented. The cross-reactivity among different forms of shellfish and immunotherapeutic approaches, including unmodified allergens, hypoallergens, peptide-based, and DNA-based vaccines, are also addressed.

EAACI Molecular Allergology User's Guide 2.0.

Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE-mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE-mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well-defined, highly pure molecules for component-resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the "EAACI Molecular Allergology User's Guide" (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state-of-the-art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure.

Differential patterns of fish sensitization in Asian populations: Implication for precision diagnosis.

BACKGROUND: The current diagnostics of fish allergy lack sufficient accuracy such that more reliable tests such as component-resolved diagnosis (CRD) are urgently needed. This study aimed at identifying fish allergens of salmon and grass carp and evaluating the sensitization pattern in fish allergic subjects from two distinct populations in Asia. METHODS: One hundred and three fish allergic subjects were recruited from Hong Kong (67 subjects) and Japan (46 subjects). Western blot and mass spectrometry were used to identify allergens from salmon and grass carp. Fish allergens were purified and tested against 96 sera on ELISA to analyze patients' sensitization pattern. The protein profiles of salmon meat prepared under different cooking methods until core temperature reached 80 °C were evaluated by SDS-PAGE and mass spectrometry. RESULTS: Three common allergens between salmon and grass carp, namely enolase, glycerldehyde-3-phosphate dehydrogenase (GAPDH) and parvalbumin, and two salmon-specific allergens collagen and aldolase were identified. Parvalbumin was the major allergen for both fishes showing an overall sensitization rate of 74.7%, followed by collagen (38.9%), aldolase (38.5%) and enolase (17.8%). Japanese subjects showed more diverse allergen sensitization pattern and more frequent IgE-binding to heat-labile salmon allergens. Compared with steaming and boiling, cooking by baking and frying retained more fish proteins inclusive of heat-labile allergens. CONCLUSIONS: Fish allergic patients from different Asian populations show varying fish allergen sensitization profiles. The relevant extracts and components for diagnosis are population-dependent but parvalbumin and collagen are important biomarkers. Cooking methods modify allergen composition of salmon and appear to influence patients' allergic manifestations.

House dust mite allergy: The importance of house dust mite allergens for diagnosis and immunotherapy.

House dust mite (HDM) allergy belongs to the most important allergies and affects approximately 65-130 million people worldwide. Additionally, untreated HDM allergy may lead to the development of severe disease manifestations such as atopic dermatitis or asthma. Diagnosis and immunotherapy of HDM allergic patients are well established but are often hampered by the use of mite extracts that are of bad quality and lack important allergens. The use of individual allergens seems to be a promising alternative to natural allergen extracts, since they represent well-defined components that can easily be produced and quantified. However, a thorough characterization of the individual allergens is required to determine their clinical relevance and to identify those allergens that are required for correct diagnosis of HDM allergy and for successful immunotherapy. This review gives an update on the individual HDM allergens and their benefits for diagnosis and immunotherapy of HDM allergic patients.

Component-Resolved Analyses for Diagnosis of Food Allergies in Infants and Young Children in Southern China.

INTRODUCTION: Chicken eggs and cow's milk are two of the most common foods that cause allergic reactions in infants and young children, and there is a lack of precise diagnostic methods to identify the allergic state of these patients. The recently developed food allergen component-resolved diagnosis (CRD) may be a more accurate diagnosis method for food allergies. METHODS: One hundred children sensitized to egg white and milk crude extracts and diagnosed with or suspected allergic disease were included. The specific immunoglobulin E (sIgE) (s) of animal food allergen crude extracts (egg yolk, milk, shrimp, crab, cod, beef) and the main components of egg white and milk were tested. The sensitization characteristics, cross-reactivity, and clinical relevance were analyzed. RESULTS: The results of egg white-sensitized patients showed that ovalbumin (Gal d 2) had the highest positive rate of 100%. Compared with other pairwise combinations of egg allergens, the combination of egg white and Gal d 2 had higher diagnostic accuracy, with an AUC of 0.876 (95% CI: 0.801-0.951), a sensitivity of 88.9%, and a specificity of 75.9%. The positive rates of beta-lactoglobulin (Bos d 5) and alpha-lactoglobulin (Bos d 4) in the milk-sensitized children were comparable, 92% and 91%, respectively. The combination of crude milk extract and Bos d 4 had the highest diagnostic accuracy, with an AUC of 0.969 (95% CI: 0.938-0.999), a sensitivity of 100%, and a specificity of 82.7%. CONCLUSION: Among these subjects, our study found the main allergenic component of egg white was Gal d 2, and the main allergenic components of milk were Bos d 4 and Bos d 5. CRD may help identify egg/milk allergies and non-allergies.

Natural History of Hazelnut Allergy and Current Approach to Its Diagnosis and Treatment.

Hazelnut allergy is the most prevalent type of nut allergy in Europe, with symptoms that can range from mild, such as hives and itching, to severe, such as anaphylaxis, particularly in patients who are sensitized to highly stable allergens, such as storage proteins. Compared to other types of food allergies, allergies to tree nuts, including hazelnuts, tend to persist throughout life. Although symptoms can appear in early childhood, they often continue into adulthood, with a minority of cases improving during adolescence. Currently, there is no curative treatment available for hazelnut allergy, and patients must adhere to a restrictive diet and carry autoinjective epinephrine. However, oral allergen immunotherapy (AIT) is a promising treatment option. Patients can be categorized based on their risk for severe reactions using various clinical, in vivo, and in vitro tests, including component-resolved diagnosis and oral food challenge. This review aims to provide an overview of the current knowledge of the natural history of hazelnut allergy and new approaches for its diagnosis and management.

Characteristics of Allergen Components of Dermatophagoides pteronyssinus in Shrimp and Mite Co-Sensitized Patients in Southern China.

INTRODUCTION: Dermatophagoides pteronyssinus (Dp) and shrimp are common air allergens and allergenic food sources, respectively, in southern China. This study aimed to analyze the specific immunoglobulin E (sIgE) characteristics and relationships of Dp components among co-sensitized patients with Dp and shrimp. MATERIALS AND METHODS: Serum samples were collected from 112 patients with Dp sensitization (61 with shrimp sensitization and 51 without) from southern China. The sIgE concentrations of Dp and shrimp crude extracts were determined by ImmunoCAP, and the sIgE of Dp allergen components (Der p 1, Der p 2, Der p 5, Der p 7, Der p 10, Der p 21, and Der p 23) was detected by protein chip. RESULTS: Overall, in the Dp-allergic patients, Der p 1 had the highest positive rate (72.3%), followed by Der p 2 (65.2%), Der p 23 (46.4%), Der p 7 (32.14%), Der p 21 (29.46%), Der p 5 (22.32%), and Der p 10 (17.86%). Compared with that in the shrimp nonsensitized group, the positive rate of sIgE for Der p 10 (27.87% vs. 5.88%, p = 0.002) in the shrimp sensitization group was significantly higher; however, the positive rate of sIgE for Der p 7 (22.95% vs. 43.14%, p = 0.023) was significantly lower. Moreover, the concentration of sIgE for Der p 10 increased statistically in the shrimp-sensitized group. The correlation analysis also showed that shrimp sensitization was significantly correlated with Der p 10. CONCLUSION: Among patients with Dp sensitization, Der p 1 had the highest positive rate, followed by Der p 2 and Der p 23. Meanwhile, Der p 10 may play an important role in patients with shrimp sensitization, while Der p 7 may be the meaningful allergen component in patients with Dp sensitization alone. In general, component-resolved diagnosis technology in clinical practice can effectively guide patients with polysensitization to avoid allergic substances.

IgE-mediated Anisakis allergy in children.

Anisakids are nematodes responsible for different clinical patterns in humans. The well-known human-infecting Anisakis species include members of the Anisakis simplex (AS) complex. Humans usually contract anisakiasis through ingestion of raw or undercooked seafood containing Anisakis larvae. Once Anisakis has been ingested, patients may develop disease driven directly by Anisakis larvae and/or by allergic reaction due to this nematode. The capability of inducing allergic reactions depends on the expression of specific antigens by nematodes and host factors. This study aims to resume actual knowledge about AS and Anisakiasis with regard to epidemiology, pathophysiology, clinical presentation, diagnosis, and treatment. Particular attention is paid to Anisakis allergens and their cross-reactivity on available diagnostic methods, and defining a diagnostic pathway for Anisakis allergy. Because only a few data are available in the literature about pediatric population, we focus on this group of patients specifically.

Using Component-Resolved Diagnosis to Characterize the Sensitization to Specific Cat and Dog Allergens in Patients with Allergic Respiratory Diseases in Catalonia, Spain.

INTRODUCTION: Sensitization to cat and dog allergens is common in patients with allergic respiratory diseases. The study objective was to determine the prevalence of immunoglobulin E (IgE) sensitization to specific cat and dog allergens using component-resolved diagnosis (CRD) in patients with allergic respiratory diseases plus cat and/or dog sensitization. METHODS: We included 87 patients aged 8-62 years, diagnosed with allergic asthma and/or rhinitis plus cat and/or dog sensitization, and attended at the allergy section of a tertiary hospital in Badalona (Catalonia, Spain). We used CRD to determine IgE sensitization to specific cat/dog allergens and skin prick tests (SPTs) to determine differences between diagnostic test results. RESULTS: Patients were monosensitized to cats (20.7%) or dogs (3.4%) or sensitized to both (75.9%). The highest positive allergen rates were for Fel d 1 (91.7%) and Fel d 4 (41%) in patients sensitized to cat allergens and for Can f 5 (80%) and Can f 1 (70%) in those sensitized to dog allergens. CRD and SPT results differed somewhat: 16.1% and 27.6% of patients CRD positive for cat or dog sensitization, respectively, were SPT negative, and 6.9% SPT positive for dog sensitization were CRD negative. Few statistically significant relationships were found between any allergen components and any respiratory disease characteristic or contact with furry animals. CONCLUSIONS: CRD may be used to determine the prevalence of IgE sensitization to specific cat and dog allergens in patients with allergic respiratory diseases plus cat and/or dog sensitization. As SPT may not correctly identify all patients sensitized to cats and dogs, our results support the use of CRD.

IgE-mediated Anisakis allergy in children

Anisakids are nematodes responsible for different clinical patterns in humans. The well-known human-infecting Anisakis species include members of the Anisakis simplex (AS) complex. Humans usually contract anisakiasis through ingestion of raw or undercooked seafood containing Anisakis larvae. Once Anisakis has been ingested, patients may develop disease driven directly by Anisakis larvae and/or by allergic reaction due to this nematode. The capability of inducing allergic reactions depends on the expression of specific antigens by nematodes and host factors. This study aims to resume actual knowledge about AS and Anisakiasis with regard to epidemiology, pathophysiology, clinical presentation, diagnosis, and treatment. Particular attention is paid to Anisakis allergens and their cross-reactivity on available diagnostic methods, and defining a diagnostic pathway for Anisakis allergy. Because only a few data are available in the literature about pediatric population, we focus on this group of patients specifically (AU)