A systematic review of allergen cross-reactivity: Translating basic concepts into clinical relevance.

Access to the molecular culprits of allergic reactions allows for the leveraging of molecular allergology as a new precision medicine approach-one built on interdisciplinary, basic, and clinical knowledge. Molecular allergology relies on the use of allergen molecules as in vitro tools for the diagnosis and management of allergic patients. It complements the conventional approach based on skin and in vitro allergen extract testing. Major applications of molecular allergology comprise accurate identification of the offending allergen thanks to discrimination between genuine sensitization and allergen cross-reactivity, evaluation of potential severity, patient-tailored choice of the adequate allergen immunotherapy, and prediction of its expected efficacy and safety. Allergen cross-reactivity, defined as the recognition of 2 or more allergen molecules by antibodies or T cells of the same specificity, frequently interferes with allergen extract testing. At the mechanistic level, allergen cross-reactivity depends on the allergen, the host's immune response, and the context of their interaction. The multiplicity of allergen molecules and families adds further difficulty. Understanding allergen cross-reactivity at the immunologic level and translating it into a daily tool for the management of allergic patients is further complicated by the ever-increasing number of characterized allergenic molecules, the lack of dedicated resources, and the need for a personalized, patient-centered approach. Conversely, knowledge sharing paves the way for improved clinical use, innovative diagnostic tools, and further interdisciplinary research. Here, we aimed to provide a comprehensive and unbiased state-of-the art systematic review on allergen cross-reactivity. To optimize learning, we enhanced the review with basic, translational, and clinical definitions, clinical vignettes, and an overview of online allergen databases.

Sensitization profiles to house dust mite Dermatophagoides pteronyssinus molecular allergens in the Lithuanian population: Understanding allergic sensitization patterns.

BACKGROUND: House dust mite (HDM) allergy is a prevalent global health concern, with varying sensitization profiles observed across populations. We aimed to provide a comprehensive assessment of molecular allergen sensitization patterns in the Lithuanian population, with a focus on Dermatophagoides pteronyssinus (Der p), and investigate patterns of concomitant reactivity among different allergens to enhance the accuracy of HDM allergy diagnostics. METHODS: A comprehensive analysis of 1520 patient test results in Lithuania from 2020 to 2022 was performed. Sensitization patterns to major (Der p 1, Der p 2, and Der p 23) and minor (Der p 5, Der p 7, and Der p 21) Der p allergen components were described using molecular-based diagnostics. Additionally, we investigated sensitization to allergen components from other allergen sources, including tropomyosins (Der p 10, Per a 7, Pen m 1, Ani s 3, Blo t 10) and arginine kinases (Pen m 2, Bla g 9, Der p 20). RESULTS: This study reveals a high prevalence of HDM sensitization in Lithuania - 481 individuals (45.38% of the sensitized group) exhibited sensitization to at least one Der p allergen component. Importantly, within the sensitized group, 37.21% of patients were sensitized to Der p 5, Der p 7, or Der p 21 in addition to major allergenic components. Distinct sensitization patterns were observed across different age groups, indicating the influence of age-related factors. Furthermore, we confirmed cross-reactivity between Der p 5 and Blo t 5 as well as between Der p 21 and Blo t 21, emphasizing the clinical relevance of these associations. We also highlighted the complexity of sensitization patterns among tropomyosins and arginine kinases. CONCLUSION: This study provides valuable insights into HDM allergy sensitization profiles in Lithuania, emphasizing the importance of considering major and minor HDM allergen components for accurate diagnosis and management of HDM-related allergic diseases. Differences between populations and age-related factors impact sensitization patterns. Understanding concomitant reactivity among allergens, such as Der p 5 and Blo t 5, Der p 21 and Blo t 21, tropomyosins, and arginine kinases, is crucial for improving diagnostic strategies and developing targeted interventions for allergic individuals.

Molecular Allergology and Component-Resolved Diagnosis in Current Clinical Practice.

Specific immunoglobulin E immunodiagnostics is becoming a convenient way to identify allergic patients and their specific allergies. These results are comparable to skin testing and may be more accessible for some populations. Each allergen contains thousands of molecules but only a few of these molecules are allergenic to humans. Each allergen has a number of individual components-generally proteins-which have different characteristics that may impact the effects of sensitization. Identification of the specific component allows for differentiation of the true allergies and can help to determine the risk of a significant clinical response.

Advocacy of Precision Allergy Molecular Diagnosis in Decision Making for the Eligibility of Customized Allergen Immunotherapy.

Allergen immunotherapy (AIT) with aeroallergens is the only disease-modifying treatment for patients with different allergic conditions. Despite the effectiveness of AIT having been proven in both randomized controlled trials and real-world studies, it remains underused in less than 10% of subjects with allergic rhinitis (AR) and/or asthma (A). We aimed to determine the current eligibility for house dust mite (HDM) AIT by means of a precision allergy molecular diagnosis (PAMD@) model in a selected cohort of youngsters with different allergic phenotypes according to the available evidence. A complex response to both HDM and storage mite allergens was depicted regardless of the subjects' basal atopic condition. No solely specific IgE-binding responses to Der p 1, Der p 2, and/or Der p 23 were found in the studied cohort. Despite the patients with A and atopic dermatitis showing significantly higher serum titers to six mite allergens than subjects with AR, no specific molecular profile was regarded as disease specific. Given the increasing complexity of specific IgE responses to the local prevailing aeroallergens, the identification and presence of such molecules are needed in commercially available AIT in the era of precision medicine.

Molecular allergology and its application in prevention, diagnosis and therapy.

Allergic diseases represent a relevant global health problem, affecting adults and children and posing a significant burden for health care systems. In addition, the disease is still under-recognized and harmonized diagnostic tools and management plans for patients are still lacking. In this review the most important aspects of the diagnosis of allergic diseases are summarized and the contribution of Molecular allergology to this area is highlighted.

The History and Science of the Major Birch Pollen Allergen Bet v 1.

The term allergy was coined in 1906 by the Austrian scientist and pediatrician Clemens Freiherr von Pirquet. In 1976, Dietrich Kraft became the head of the Allergy and Immunology Research Group at the Department of General and Experimental Pathology of the University of Vienna. In 1983, Kraft proposed to replace natural extracts used in allergy diagnostic tests and vaccines with recombinant allergen molecules and persuaded Michael Breitenbach to contribute his expertise in molecular cloning as one of the mentors of this project. Thus, the foundation for the Vienna School of Molecular Allergology was laid. With the recruitment of Heimo Breiteneder as a young molecular biology researcher, the work began in earnest, resulting in the publication of the cloning of the first plant allergen Bet v 1 in 1989. Bet v 1 has become the subject of a very large number of basic scientific as well as clinical studies. Bet v 1 is also the founding member of the large Bet v 1-like superfamily of proteins with members-based on the ancient conserved Bet v 1 fold-being present in all three domains of life, i.e., archaea, bacteria and eukaryotes. This suggests that the Bet v 1 fold most likely already existed in the last universal common ancestor. The biological function of this protein was probably related to lipid binding. However, during evolution, a functional diversity within the Bet v 1-like superfamily was established. The superfamily comprises 25 families, one of which is the Bet v 1 family, which in turn is composed of 11 subfamilies. One of these, the PR-10-like subfamily of proteins, contains almost all of the Bet v 1 homologous allergens from pollen and plant foods. Structural and functional comparisons of Bet v 1 and its non-allergenic homologs of the superfamily will pave the way for a deeper understanding of the allergic sensitization process.

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.

Allergy screening with extract-based skin prick tests demonstrates higher sensitivity over in vitro molecular allergy testing.

BACKGROUND: As extract-based skin testing as well as in vitro tests for major allergens have their own advantages, both procedures are usually performed in routine settings. In times of shortages in medical staff and supplies, we asked ourselves, how many patients would be underdiagnosed, if only one test could be used. METHODS: In a retrospective analysis, we investigated a cohort of 2646 patients seen by a single physician in a large Austrian outpatient allergy clinic in 2018. Only patients with an allergen source-specific history and pairs of extract-based skin prick (SPT) and in vitro molecular allergy tests to major allergens were included. RESULTS: For all tested allergen sources, sensitivity was higher for SPT than for sIgE-based molecular allergy testing. Concerning 1006 birch pollen-allergic patients, 791 (78.6%) had positive results with both tests, while 153 (15.2%) only with the SPT and 62 (6.2%) only with the sIgE to Bet v1. The other allergen sources showed similar results: For house dust mite 816/1120 (72.9%), grass pollen 1077/1416 (76.1%) and cat 433/622 (69.6%) remained test-positive with both procedures, whereas in 276 (24.6%), 224 (15.8%) and 173 (27.8%) times only the SPT and 28 (2.5%), 115 (8.1%) and 16 (2.6%) times only the sIgE to Der p1/2/23, Phl p1/5 and Fel d1 showed a positive result. Each comparison was statistically significant (each p < 0.0001, Chi-squared test). CONCLUSIONS: Screening for allergy with major molecular allergens has lower sensitivity when compared with extract-based skin tests. A combination of both is required for an optimal sensitivity.

Development of sensitization to peanut and storage proteins and relation to markers of airway and systemic inflammation: A 24-year follow-up.

BACKGROUND: Long-time data of peanut allergy over time is sparse. We aimed to study the longitudinal development of sensitization to peanut extract and storage protein allergen molecules and associations with asthma status, airway and systemic inflammation markers. METHODS: The Swedish birth cohort BAMSE followed 4089 participants with questionnaires, clinical investigations and blood sampling between 0 and 24 years. Information on (i) background factors at 2 months, (ii) peanut allergy symptoms and IgE data (ImmunoCAP) at 4, 8, 16, and 24 years, and (iii) IgE to storage proteins, lung function data including exhaled nitric oxide (FENO) as well as systemic inflammatory markers at 24 years of age were collected. RESULTS: The prevalence of peanut extract sensitization, defined as IgE ≥ 0.35 kUA /L, was 5.4%, 8.0%, 7.5%, and 6.2% at 4, 8, 16, and 24 years of age, respectively. Between 8 and 24 years of age, (33/1565) participants developed IgE-ab to peanut extract (median 1,4, range 0.7-2.6 kUA /L), and among those 85% were also sensitized to birch. Only six individuals developed sensitization to Ara h 2 (≥0.1 kUA /L) between 8 and 24 years of age, of whom three had an IgE-ab level between 0.1-0.12 kUA /L. Storage protein sensitization was associated with elevated FENO, blood eosinophils and type 2 inflammation-related systemic proteins. CONCLUSION: Sensitization to peanut extract after 4 years of age is mainly induced by birch cross-sensitization and IgE to Ara h 2 rarely emerges after eight years of age. Storage protein sensitization is associated with respiratory and systemic inflammation.

Recent advances in diagnosing and managing nut allergies with focus on hazelnuts, walnuts, and cashew nuts.

Tree nuts are a powerful and common source of food allergens that induce IgE-mediated allergic reactions. Health authorities endorse the intake of tree nuts because they are regarded as nutritious. Allergic reactions to nuts can lead to severe and occasionally lethal reactions. Allergies to tree nuts are observed worldwide and are found in up to 4.9% of people in unspecific populations. Over the last 2 decades, the rates of allergic reactions and anaphylaxis have increased in different countries. Most proteins implicated in tree nut allergic reactions are members of the lipid transfer protein, 2S albumin, vicilin, legumin, and oleosin protein families. Bet v 1 homologs and profilins are involved in pollen-related tree nut allergies. Systematic literature reviews and meta-analyses on the diagnostic accuracy of specific immunoglobulin E (sIgE) for commercially available nut components have recently been published. IgE testing of the storage proteins Cor a 14, Cor a 9, Jug r 1, and Ana o 3 increases diagnostic specificity in assessing hazelnut, walnut, and cashew allergies in children, respectively. The resolution of tree nut allergies has been reported; however, only a few studies are available in this regard. Complete avoidance of nuts is the safest approach for nut-allergic subjects. However, this is difficult to achieve and can result in a severely restricted diet. Patients can eat nuts that they know are safe at home, but should avoid them when eating out because of the risk of cross-contamination. Nuts have become part of a modern healthy diet, and this enhanced consumption is reflected in an increased prevalence of nut allergies.

Recombinant Tropomyosin from the Pacific Oyster (Crassostrea gigas) for Better Diagnosis.

The Pacific oyster is a commercially important mollusc and, in contrast to most other shellfish species, frequently consumed without prior heat treatment. Oysters are rich in many nutrients but can also cause food allergy. Knowledge of their allergens and cross-reactivity remains very limited. These limitations make an optimal diagnosis of oyster allergy difficult, in particular to the Pacific oyster (Crassostrea gigas), the most cultivated and consumed oyster species worldwide. This study aimed to characterise IgE sensitisation profiles of 21 oyster-sensitised patients to raw and heated Pacific oyster extract using immunoblotting and advanced mass spectrometry, and to assess the relevance of recombinant oyster allergen for improved diagnosis. Tropomyosin was identified as the major allergen recognised by IgE from 18 of 21 oyster-sensitised patients and has been registered with the WHO/IUIS as the first oyster allergen (Cra g 1). The IgE-binding capacity of oyster-sensitised patients' IgE to purified natural and recombinant tropomyosin from oyster, prawn, and dust mite was compared using enzyme-linked immunosorbent assay. The degree of IgE binding varied between patients, indicating partial cross-sensitisation and/or co-sensitisation. Amino acid sequence alignment of tropomyosin from these three species revealed five regions that contain predicted IgE-binding epitopes, which are most likely responsible for this cross-reactivity. This study fully biochemically characterises the first and major oyster allergen Cra g 1 and demonstrates that the corresponding recombinant tropomyosin should be implemented in improved component-resolved diagnostics and guide future immunotherapy.

[Food sensitivities of the digestive tract-Part 1: Food allergies]. / Nahrungsmittelunverträglichkeiten des Verdauungstraktes ­ Teil 1: Nahrungsmittelallergien.

Adverse reactions to food affect approximately one third of the population. They are based on very different mechanisms and are divided into food intolerances, which manifest mainly in the gastrointestinal tract, and food allergies, which can also cause extraintestinal symptoms and have an immunological genesis. The most common food allergies in adults are pollen-associated allergies to cereals or pome and stone fruits, while allergies to peanut, milk and egg are particularly common in children. The diagnostics of food allergies are complex and therapy is primarily based on targeted elimination diets. This advanced education article focuses on food allergies with gastrointestinal symptoms.

Food allergy and hypersensitivity reactions in children and adults-A review.

Adverse reactions after food intake are commonly reported and a cause of concern and anxiety that can lead to a very strict diet. The severity of the reaction can vary depending on the type of food and mechanism, and it is not always easy to disentangle different hypersensitivity diagnoses, which sometimes can exist simultaneously. After a carefully taken medical history, hypersensitivity to food can often be ruled out or suspected. The most common type of allergic reaction is immunoglobulin E (IgE)-mediated food allergy (prevalence 5-10%). Symptoms vary from mild itching, stomach pain, and rash to severe anaphylaxis. The definition of IgE-mediated food allergy is allergic symptoms combined with specific IgE-antibodies, and therefore only IgE-antibodies to suspected allergens should be analyzed. Nowadays, methods of molecular allergology can help with the diagnostic process. The most common allergens are milk and egg in infants, peanut and tree nuts in children, and fish and shellfish in adults. In young children, milk/egg allergy has a good chance to remit, making it important to follow up and reintroduce the food when possible. Other diseases triggered by food are non-IgE-mediated food allergy, for example, eosinophilic esophagitis, celiac disease, food protein-induced enterocolitis syndrome, and hypersensitivity to milk and biogenic amines. Some of the food hypersensitivities dominate in childhood, others are more common in adults. Interesting studies are ongoing regarding the possibilities of treating food hypersensitivity, such as through oral immunotherapy. The purpose of this review was to provide an overview of the most common types of food hypersensitivity reactions.

Prevalence and early-life risk factors for tree nut sensitization and allergy in young adults.

BACKGROUND: Tree nut allergy may cause anaphylaxis. There are limited population-based studies on prevalence and early-life risk factors. METHODS: We evaluated the prevalence of reported symptoms and allergic sensitization to tree nuts at age 24 years in the BAMSE population-based cohort study and assessed early-life factors associated with the development of tree nut allergy. We estimated tree nut allergy prevalence, by analysing questionnaire data on tree nut ingestion and symptoms at age 12, 16 and 24 years, and IgE sensitization at age 24 years to hazelnut, walnut, pecan, cashew, pistachio, Brazil nut, almond extracts and allergen molecules Cor a 1, 9, 14 (hazelnut), Jug r 1 (walnut) and Ana o 3 (cashew). We evaluated eczema, asthma, food allergies, inherited risk of allergy and gender as potential early-life risk factors. RESULTS: Data were available for 2215/4089 (54%) BAMSE study participants, for estimation of the prevalence of tree nut sensitization (21.2%), tree nut allergy symptoms (9.8%) and combined sensitization and symptoms (7.9%, 2.1% for storage protein sensitization and symptoms, 4.3% for any sensitization and non-mild symptoms). Sixty-three per cent of sensitized individuals (295/470) were asymptomatic, but only 76/470 (16%) storage protein sensitized individuals. Egg allergy (ORadj 8.50 95% CI 2.15-33.6), eczema (ORadj 2.53 95% CI 1.21-5.32) and asthma (ORadj 5.59 95% CI 2.35-13.3)) at pre-school age were associated with future development of tree nut symptoms and storage protein sensitization. At age 24 years, tree nut allergy was associated with current eczema and with markers of current asthma severity. Sensitization to storage proteins was more strongly associated with symptoms than sensitization to whole extract for all tree nuts evaluated. CONCLUSIONS: In this Swedish cohort, we found tree nut whole extract sensitization is common but usually asymptomatic. Storage protein sensitization is a more reliable indicator of tree nut symptoms. Tree nut allergy is associated with early onset, persistent and severe atopic disease.

New technologies in molecular allergodiagnostics.

The article presents the characteristics of the ALEX2 (MacroArrayDX, Wien, Austria). It is designed for simultaneous detection of IgE total and specific IgE-aB to 120 extracts and 180 molecules by solid-phase enzyme immunoassay. Extracts and allergen molecules combined with nano-particles are sorbed on a solid-phase substrate, forming a macroscopic multiplex matrix - the immune allergy chip. The Institute of Clinical and Laboratory Standards (CLSI) conducted research on the verification and validation of the ALEX2 in relation to the ImmunoCAP macroarray test system (ThermoFisher Scientific, Uppsala, Sweden), which is often used in allergodiagnostics. The results obtained on the two test systems were comparable. One of the most important features of the ALEX2 test system is that unique allergen molecules and allergenic extracts are included in its composition, and a method has been found to inhibit cross-reactive hydrocarbon determinants (CCDs), which cause frequent non-specific binding of IgE-aT. The use of this test system makes it possible to carry out component allergy diagnostics with the determine of the dominant sensitizing factor in cases of mono- and polyvalent sensitization. The test results affect the determination of indications and the effectiveness of ASIT, allow assessing the risk of anaphylaxis and predicting further treatment tactics for the patient.

Allergen extract- and component-based diagnostics in children of the ALLIANCE asthma cohort.

BACKGROUND: Current in vitro allergen-specific IgE (sIgE) detection assays measure IgE against allergen extracts or molecules in a single- or multiplex approach. Direct comparisons of the performance of such assays among young children with common presentations of allergic diseases regardless of sensitization status are largely missing. OBJECTIVES: The aim of this study was a comparison of the analytical and diagnostic performance for common clinical questions of three commonly used technologies which rely upon different laboratory methodologies among children of the All Age Asthma (ALLIANCE) cohort (clinicaltrials.gov: NCT02496468). METHODS: Sera from 106 paediatric study participants (mean age 4 years) were assessed for the presence of sIgE by means of the ImmunoCAP™ sx1 and fx5 mixes, the ImmunoCAP ISAC™ 112 microarray and a Euroline™ panel. RESULTS: Total and negative concordance was high (>82%->89%), while positive concordance varied considerably (0%-100%) but was also >50% for the most common sensitizations analysed (house dust mite and birch). All three test systems showed good sensitivity and specificity (AUC consistently > 0.7). However, no significant differences with regard to identifying sIgE sensitizations associated with symptoms in children with suspected pollen- or dust-triggered wheeze or presenting with symptoms of allergic rhinoconjunctivitis or food allergy were detected. Extending the number of allergens did not change the similar performance of the three assay systems. CONCLUSION AND CLINICAL RELEVANCE: Among young children, the three sIgE assays showed good analytical and diagnostic concordance. Our results caution that the identification of larger numbers of sensitizations by more comprehensive multiplex approaches may not improve the clinical utility of sIgE testing in this age group.

The importance of component-resolved diagnostics in IgE-mediated cow's milk allergy.

Cow's milk allergy (CMA) is an increasingly common problem among children and adults that requires the use of appropriate diagnostics to eliminate allergic reactions and prevent unnecessary dietary regimes. The current diagnostics methods are imperfect hence new, more effective methods are still being sought. Component-resolved diagnostics (CRD) is one of them. CRD assesses sensitivity to individual allergen molecules using purified native or recombinant allergens. The present paper reviews the role of CRD in diagnosing CMA, as well as the benefits and limitations of its use, especially in predicting allergy development or acquiring immunotolerance. It examines the possibility of replacing the current gold diagnostic standard with component tests directed against specific milk proteins. In addition, CRD could be helpful in the evaluation of prognosis. However, CRD allows for improvement in clinical management, particularly of polysensitized subjects, there is still no cogent evidence that it offers more efficient CMA diagnostics than existing tests.

The importance of component-resolved diagnostics in IgE-mediated cow’s milk allergy

Cow’s milk allergy (CMA) is an increasingly common problem among children and adults that requires the use of appropriate diagnostics to eliminate allergic reactions and prevent unnecessary dietary regimes. The current diagnostics methods are imperfect hence new, more effective methods are still being sought. Component-resolved diagnostics (CRD) is one of them. CRD assesses sensitivity to individual allergen molecules using purified native or recombinant allergens. The present paper reviews the role of CRD in diagnosing CMA, as well as the benefits and limitations of its use, especially in predicting allergy development or acquiring immunotolerance. It examines the possibility of replacing the current gold diagnostic standard with component tests directed against specific milk proteins. In addition, CRD could be helpful in the evaluation of prognosis. However, CRD allows for improvement in clinical management, particularly of polysensitized subjects, there is still no cogent evidence that it offers more efficient CMA diagnostics than existing tests (AU)

Extract and molecular-based early infant sensitization and associated factors-A PreventADALL study.

BACKGROUND: More knowledge about sensitization patterns in early infancy, including impact of molecular allergology, is needed to help predict future allergy development more accurately. OBJECTIVE: We aimed to determine the prevalence and patterns of allergic sensitization at 3 months of age, and explore possible associated factors. METHODS: From the Scandinavian antenatally recruited PreventADALL mother-child cohort, we included 1110 3-month infants with available serum. Sensitization was defined as s-IgE of ≥0.1 kUA /L by Phadiatop Infant® (ThermoFisher Scientific) including birch, cat, grass, dog, milk, egg, peanut and wheat. Further ImmunoCAP analyses to ovomucoid, casein, Ara h 1-3, omega-5-gliadin were performed in food extract s-IgE-positive children. Maternal sensitization was defined as s-IgE ≥ 0.35 kUA /L to Phadiatop® (inhalant allergen mix) and/or Fx5 (food allergen mix) at 18-week pregnancy. RESULTS: Overall 79 (7.3%) infants had specific sensitization, many with low s-IgE-levels (IQR 0.16-0.81 kUA /L), with 78 being sensitized to food extract allergens; 41 to egg, 27 to milk, 10 to peanut, and 25 to wheat. A total of 62/78 were further analysed, 18 (29%) had s-IgE to ovomucoid, casein, Ara h 1-3 and/or omega-5-gliadin. Eight infants (0.7%) were sensitized to inhalant allergens. Maternal sensitization to food allergens was associated with infant sensitization, odds ratio 3.64 (95% CI 1.53-8.68). CONCLUSION: Already at 3 months of age, 7% were sensitized to food, mostly without detectable s-IgE to food allergen molecules, and <1% to inhalant allergens. Maternal food sensitization was associated with infants' sensitization.

Basophil activation test shows high accuracy in the diagnosis of peanut and tree nut allergy: The Markers of Nut Allergy Study.

BACKGROUND: Peanut and tree nut allergies are the most important causes of anaphylaxis. Co-reactivity to more than one nut is frequent, and co-sensitization in the absence of clinical data is often obtained. Confirmatory oral food challenges (OFCs) are inconsistently performed. OBJECTIVE: To investigate the utility of the basophil activation test (BAT) in diagnosing peanut and tree nut allergies. METHODS: The Markers Of Nut Allergy Study (MONAS) prospectively enrolled patients aged 0.5-17 years with confirmed peanut and/or tree nut (almond, cashew, hazelnut, pistachio, walnut) allergy or sensitization from Canadian (n = 150) and Austrian (n = 50) tertiary pediatric centers. BAT using %CD63+ basophils (SSClow/CCR3pos) as outcome was performed with whole blood samples stimulated with allergen extracts of each nut (0.001-1000 ng/mL protein). BAT results were assessed against confirmed allergic status in a blinded fashion to develop a generalizable statistical model for comparison to extract and marker allergen-specific IgE. RESULTS: A mixed effect model integrating BAT results for 10 and 100 ng/mL of peanut and individual tree nut extracts was optimal. The area under the ROC curve (AUROC) was 0.98 for peanut, 0.97 for cashew, 0.92 for hazelnut, 0.95 for pistachio, and 0.97 for walnut. The BAT outperformed sIgE testing for peanut or hazelnut and was comparable for walnut (AUROC 0.95, 0.94, 0.92) in a sub-analysis in sensitized patients undergoing OFC. CONCLUSIONS: Basophil activation test can predict allergic clinical status to peanut and tree nuts in multi-nut-sensitized children and may reduce the need for high-risk OFCs in patients.