IgE-Mediated Allergy and Asymptomatic Sensitization to Cannabis Allergens-Review of Current Knowledge and Presentation of Six Cases.

Cannabis allergy is a relatively new phenomenon described in the 1970s. Its increased frequency has been observed over the last years due to the increasing therapeutic and recreational use of cannabis-based products. Sensitization possibly leading to allergy symptoms can occur not only through the smoking of cannabis, but also through ingestion, the inhalation of pollen, or direct contact. The severity of symptoms varies from benign pruritus to anaphylaxis. There is scant information available to support clinicians throughout the entire therapeutic process, starting from diagnosis and ending in treatment. In this review, we present six cases of patients in whom molecular in vitro testing revealed sensitization to cannabis extract and/or cannabis-derived nsLTP molecules (Can s 3). Based on these cases, we raise important questions regarding this topic. The article discusses current proposals and highlights the importance of further research not only on cannabis allergy but also on asymptomatic sensitization to cannabis allergens, which may be ascertained in some percentage of the population.

IgE-Mediated Sensitization to Blo t 21 and Blo t 5 Is Associated With Asthma in the Tropics: A Case-Control Study.

BACKGROUND AND OBJECTIVE: Sensitization to Blomia tropicalis is associated with asthma in various tropical and subtropical countries; however, information about the specific molecular components associated with this disease is scarce. Using molecular diagnosis, we sought to identify B tropicalis allergens associated with asthma in Colombia. METHODS: Specific IgE (sIgE) to 8 B tropicalis recombinant allergens (Blo t 2, 5, 7, 8, 10, 12, 13, and 21) was determined using an in-house ELISA system in asthma patients (n=272) and controls (n=298) recruited in a national prevalence study performed in several Colombian cities (Barranquilla, Bogotá, Medellín, Cali, and San Andrés). The study sample included children and adults (mean [SD] age, 28 [17] years). Cross-reactivity between Blo t 5 and Blo t 21 was evaluated using ELISA-inhibition. RESULTS: Specific IgE (sIgE) to 8 B tropicalis recombinant allergens (Blo t 2, 5, 7, 8, 10, 12, 13, and 21) was determined using an in-house ELISA system in asthma patients (n=272) and controls (n=298) recruited in a national prevalence study performed in several Colombian cities (Barranquilla, Bogotá, Medellín, Cali, and San Andrés). The study sample included children and adults (mean [SD] age, 28 [17] years). Cross-reactivity between Blo t 5 and Blo t 21 was evaluated using ELISA-inhibition. CONCLUSION: Although Blo t 5 and Blo t 21 are considered common sensitizers, this is the first report of their association with asthma. Both components should be included in molecular panels for diagnosis of allergy in the tropics.

Worldwide Heterogeneity of Food Allergy: Focus on Peach Allergy in Southern Italy.

Food allergy (FA) has shown an increasing prevalence in the last decades, becoming a major public health problem. However, data on the prevalence of FA across the world are heterogeneous because they are influenced by several factors. Among IgE-mediated FA, an important role is played by FA related to plant-derived food which can result from the sensitization to a single protein (specific FA) or to homologous proteins present in different foods (cross-reactive FA) including non-specific lipid transfer proteins (nsLTPs), profilins, and pathogenesis-related class 10 (PR-10). In addition, the clinical presentation of FA is widely heterogeneous ranging from mild symptoms to severe reactions up to anaphylaxis, most frequently associated with nsLTP-related FA (LTP syndrome). Considering the potential life-threatening nature of nsLTP-related FA, the patient's geographical setting should always be taken into account; thereby, it is highly recommended to build a personalized approach for managing FA across the world in the precision medicine era. For this reason, in this review, we aim to provide an overview of the prevalence of nsLTP-mediated allergies in the Mediterranean area and to point out the potential reasons for the different geographical significance of LTP-driven allergies with a particular focus on the allergenic properties of food allergens and their cross reactivity.

Component-specific clusters for diagnosis and prediction of allergic airway diseases.

BACKGROUND: Previous studies which applied machine learning on multiplex component-resolved diagnostics arrays identified clusters of allergen components which are biologically plausible and reflect the sources of allergenic proteins and their structural homogeneity. Sensitization to different clusters is associated with different clinical outcomes. OBJECTIVE: To investigate whether within different allergen component sensitization clusters, the internal within-cluster sensitization structure, including the number of c-sIgE responses and their distinct patterns, alters the risk of clinical expression of symptoms. METHODS: In a previous analysis in a population-based birth cohort, by clustering component-specific (c-s)IgEs, we derived allergen component clusters from infancy to adolescence. In the current analysis, we defined each subject's within-cluster sensitization structure which captured the total number of c-sIgE responses in each cluster and intra-cluster sensitization patterns. Associations between within-cluster sensitization patterns and clinical outcomes (asthma and rhinitis) in early-school age and adolescence were examined using logistic regression and binomial generalized additive models. RESULTS: Intra-cluster sensitization patterns revealed specific associations with asthma and rhinitis (both contemporaneously and longitudinally) that were previously unseen using binary sensitization to clusters. A more detailed description of the subjects' within-cluster c-sIgE responses in terms of the number of positive c-sIgEs and unique sensitization patterns added new information relevant to allergic diseases, both for diagnostic and prognostic purposes. For example, the increase in the number of within-cluster positive c-sIgEs at age 5 years was correlated with the increase in prevalence of asthma at ages 5 and 16 years, with the correlations being stronger in the prediction context (e.g. for the largest 'Broad' component cluster, contemporaneous: r = .28, p = .012; r = .22, p = .043; longitudinal: r = .36, p = .004; r = .27, p = .04). CONCLUSION: Among sensitized individuals, a more detailed description of within-cluster c-sIgE responses in terms of the number of positive c-sIgE responses and distinct sensitization patterns, adds potentially important information relevant to allergic diseases.

IgE to cyclophilins in pollen-allergic children: Epidemiologic, clinical, and diagnostic relevance of a neglected panallergen.

BACKGROUND: Cyclophilins are ubiquitous panallergens whose epidemiologic, diagnostic, and clinical relevance is largely unknown and whose sensitization is rarely examined in routine allergy practice. OBJECTIVE: We investigated the epidemiologic, diagnostic, and clinical relevance of cyclophilins in seasonal allergic rhinitis and its comorbidities. METHODS: We examined a random sample of 253 (25%) of 1263 Italian children with seasonal allergic rhinitis from the Panallergens in Pediatrics (PAN-PED) cohort with characterized disease phenotypes. Nested studies of sensitization prevalence, correlation, and allergen extract inhibition were performed in patients sensitized to birch pollen extract but lacking IgE to Bet v 1/2/4 (74/1263) or with highest serum level of IgE to Bet v 1 (26/1263); and in patients with sensitization to various extracts (ragweed, mugwort, pellitory, Plantago, and plane tree), but not to their respective major allergenic molecule, profilins, and polcalcins. IgE to cyclophilin was detected with recombinant Bet v 7, and extract inhibition tests were performed with the same rBet v 7. RESULTS: IgE to rBet v 7 was detected in 43 (17%) of 253 patients. It was associated with asthma (P < .028) and oral allergy syndrome (P < .017) in univariate but not multivariate analysis adjusted for IgE to profilins (Phl p 12), PR-10s (Bet v 1), and lipid transfer proteins (Pru p 3). IgE to rBet v 7 was also highly prevalent (47/74, 63%) among patients with unexplained sensitization to birch pollen extract. In patients with unexplained sensitization to ragweed, mugwort, pellitory, Plantago and plane tree pollen, the levels of IgE to those extracts correlated with the levels of IgE to rBet v 7, and they were also significantly inhibited by rBet v 7 (inhibition range 45%-74%). CONCLUSIONS: IgE sensitization to cyclophilin is frequent in pollen-allergic patients living in temperate areas and can produce "false" positive outcomes in skin prick and IgE tests to pollen extracts. Molecular diagnostic guidelines should include this panallergen family.

Molecular profiling in bee venom allergy: clinical and therapeutic characterization in a Portuguese cohort.

Summary: Background. Bee venom allergy (BVA) can trigger local and systemic allergic reactions, including anaphylaxis. Recently, the molecular sensitization profile has gained importance in the reaction's stratification and venom immunotherapy (VIT). Methods. Retrospective analysis of patients with hypersensitivity to BVA, confirmed by specific sIgE to Apis mellifera ≥0.35 kU/L and/or positive skin tests to bee venom commercial extract, evaluated in specialized consultation. Demographic, clinical, and laboratory data (including molecular Api m 1, 4, and 10) were analyzed, looking for risk factors associated with the severity of the index reaction and reactions during VIT. Results. 93 patients were included (55.9% male; median age of 46 years), 57.3% with atopic comorbidities, and 23.4% with cardiovascular comorbidities. The median specific IgE to Apis mellifera was 6.7 kU/L (IQR 1.0-20.3) kU/L. Regarding the molecular profile, the median IgE to Api m 1 was 0.5 kU/L (57.5% positive out of all measurements); Api m 4 - 0.01 kU/L (11.9% positive), and Api m 10 - 0.3 kU/L (50.0% positive). No patient was monosensitized to Api m 4. The median age of the most severe sting reaction was 36 (IQR 26-48) years, with a median severity (Müeller scale) of 3 (IQR 2-3). Forty-seven patients (50.5%) underwent VIT, with 35.6% of reactions recorded. Allergic reactions during VIT were recorded in 35.6% of cases. The severity of the index reaction correlated positively with older ages (p=0.040; r=0.249), in contrast to monosensitization to Api m 1, which was an independent predictor of milder reactions (p=0.015). Sensitization to Api m 10 was associated with a higher likelihood of reactions during VIT (p=0.038) but potentially less systemic reactions at re-stings (p=0.097). Conclusions. Molecular sensitization profile appears to be relevant not only to the severity of index reactions but also during VIT. Studies of a large cohort of patients with molecular profiles are essential to validate these results and improve the clinical and therapeutic approach to BVA.

Ockham's Razor: The Application of Parsimonious Medicine in Allergy/Immunology.

The spectacular advances of modern medicine have distracted clinicians from applying the age-old principles of thorough history and examination followed by only ordering tests relevant to the patient's presentation. The most obvious diagnosis is the most likely and should be addressed first. Ockham's razor, or parsimonious medicine, should be applied because plurality of diagnoses is less likely than a single explanation. Component-resolved diagnostics and biological therapies for allergy/immune-mediated diseases have been highly effective when used by specialist allergy services. However, they are accessed too easily and frequently, either before diagnostically appropriate allergy skin testing and challenge have been employed or before the reasons for poor disease control have been investigated. The current fashion to test for vitamin D insufficiency in patients with poorly controlled allergic diseases has rarely achieved benefit but significantly increased costs. There are considerable health/economic benefits from following the proven value of a thorough clinical history, examination, focused allergy/immunology testing, and the judicious use of Ockham's razor.

Heterogeneity of sensitization profiles and clinical phenotypes among patients with seasonal allergic rhinitis in Southern European countries-The @IT.2020 multicenter study.

BACKGROUND: Pollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach. OBJECTIVE: To describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach. METHODS: Within the @IT.2020 multicenter observational study, pediatric and adult patients suffering from SAR were recruited in nine urban study centers located in seven countries. Clinical questionnaires, skin prick tests (SPT) and specific IgE (sIgE) tests with a customized multiplex assay (Euroimmun Labordiagnostika, Lübeck, Germany) were performed. RESULTS: Three hundred forty-eight children (mean age 13.1 years, SD: 2.4 years) and 467 adults (mean age 35.7 years SD: 10.0 years) with a predominantly moderate to severe, persistent phenotype of SAR were recruited. Grass pollen major allergenic molecules (Phl p 1 and/or Phl p 5) ranged among the top three sensitizers in all study centers. Sensitization profiles were very heterogeneous, considering that patients in Rome were highly poly-sensitized (sIgE to 3.8 major allergenic molecules per patient), while mono-sensitization was prominent and heterogeneous in other cities, such as Marseille (sIgE to Cup a 1: n = 55/80, 68.8%) and Messina (sIgE to Par j 2: n = 47/82, 57.3%). Co-sensitization to perennial allergens, as well as allergic comorbidities also broadly varied between study centers. CONCLUSIONS: In Southern European countries, pollen allergy is heterogeneous in terms of sensitization profiles and clinical manifestations. Despite the complexity, a unique molecular, multiplex, and customized in-vitro IgE test detected relevant sensitization in all study centers. Nevertheless, this geographical diversity in pollen allergic patients imposes localized clinical guidelines and study protocols for clinical trials of SAR in this climatically complex region.

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.

Systematic review and meta-analyses on the accuracy of diagnostic tests for IgE-mediated food allergy.

The European Academy of Allergy and Clinical Immunology (EAACI) is updating the Guidelines on Food Allergy Diagnosis. We aimed to undertake a systematic review of the literature with meta-analyses to assess the accuracy of diagnostic tests for IgE-mediated food allergy. We searched three databases (Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID)) for diagnostic test accuracy studies published between 1 October 2012 and 30 June 2021 according to a previously published protocol (CRD42021259186). We independently screened abstracts, extracted data from full texts and assessed risk of bias with QUADRAS 2 tool in duplicate. Meta-analyses were undertaken for food-test combinations for which three or more studies were available. A total of 149 studies comprising 24,489 patients met the inclusion criteria and they were generally heterogeneous. 60.4% of studies were in children ≤12 years of age, 54.3% were undertaken in Europe, ≥95% were conducted in a specialized paediatric or allergy clinical setting and all included oral food challenge in at least a percentage of enrolled patients, in 21.5% double-blind placebo-controlled food challenges. Skin prick test (SPT) with fresh cow's milk and raw egg had high sensitivity (90% and 94%) for milk and cooked egg allergies. Specific IgE (sIgE) to individual components had high specificity: Ara h 2-sIgE had 92%, Cor a 14-sIgE 95%, Ana o 3-sIgE 94%, casein-sIgE 93%, ovomucoid-sIgE 92/91% for the diagnosis of peanut, hazelnut, cashew, cow's milk and raw/cooked egg allergies, respectively. The basophil activation test (BAT) was highly specific for the diagnosis of peanut (90%) and sesame (93%) allergies. In conclusion, SPT and specific IgE to extracts had high sensitivity whereas specific IgE to components and BAT had high specificity to support the diagnosis of individual food allergies.

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.

Peanut Allergy and Component-Resolved Diagnostics Possibilities-What Are the Benefits?

Peanut allergy is a widespread and potentially life-threatening condition that affects both children and adults, with a growing incidence worldwide. It is estimated to affect around 1-2% of the population in several developed countries. Component-resolved diagnostics is a modern approach to allergy diagnosis that focuses on identifying specific allergenic proteins to provide precise diagnoses and personalized treatment plans. It is a technique that enables the analysis of specific IgE antibodies against tightly defined molecules (components) that constitute the allergen. Component-resolved diagnostics is particularly valuable in peanut allergy diagnosis, helping to determine allergen components associated with severe reactions. It also aids in predicting the course of the allergy and enables the development of personalized immunotherapy plans; however, the full application of it for these purposes still requires more precise studies. In this paper, we present the current knowledge about peanut allergy and component-resolved diagnostics possibilities. We discuss the possibilities of using molecular diagnostics in the diagnosis of peanut allergy. We focus on examining and predicting the development of peanut allergy, including the risk of anaphylaxis, and describe the latest data related to desensitization to peanuts.

Jug r 1 sensitization in 0- to 35-month-old children with egg, milk, or wheat sensitization.

Background: The incidence of tree nut allergies in children is increasing, with walnut allergy being the most common in the United States and Japan. Allergic reactions, including anaphylaxis, frequently occur at the first intake of tree nuts, suggesting prior sensitization. Objective: Our aim was to identify which children should be considered for workup for preexisting sensitization. Methods: Juglans regia (Jug r) 1-specific IgE screening for 0- to 35-month-old children who had a positive specific IgE result for egg white, milk, or wheat and had never ingested walnuts was conducted at a food allergy referral hospital between November 2018 and December 2022. Clinical data regarding age; sex; allergic disease complications; and egg, milk, or wheat allergy were examined retrospectively. Results: The rate of Jug r 1-specific IgE positivity (level > 0.34 kUA/L) of 205 children (125 of whom were boys) was 9.8%, with a median Jug r 1-specific IgE level of 12.5 kUA/L in patients with a positive test result. Eczema was observed in 119 patients (58%). The rate of Jug r 1-specific IgE positivity was significantly higher in the eczema-positive group (15.1% [18 of 119]) than in the eczema-negative group (2.3% [2 of 86]) (P = .002). In the eczema-positive group, the rates of Jug r 1-specific IgE positivity per sensitized antigen were 13.7% for egg, 17.0% for milk, and 17.1% for wheat. The rate of Jug r 1-specific IgE positivity was significantly higher in the group with severe eczema (26.6% [17 of 64]) than in the group with nonsevere eczema (1.8% [1 of 55]) (P < .001). Conclusion: Even in children younger than 3 years, 15% of children with eczema and egg, milk, or wheat sensitization were sensitized to Jug r 1.

Molecular sensitization patterns to cat and dog allergens in Lithuanian children population.

Background: Over the last few decades, there was observed an increase of asthma and allergic rhinitis cases caused by allergy to pets. Objective: This study aimed to analyze molecular sensitization patterns to dog and cat allergens in Lithuanian children who were experiencing allergy-like symptoms. Materials and methods: A total of 574 children (0-18 years) were tested for allergen-specific immunoglobulin E (sIgE) levels with ALEX2 (ALEX2®, Allergy Explorer Test System). Positive sera were further analyzed for sensitization to cat (Fel d 1, Fel d 2, Fel d 4, and Fel d 7) and dog (Can f 1, Can f 2, Can f 3, Can f 4, Can f 5, and Can f 6) allergen components. Results: Two hundred forty-seven children tested positive (sIgE ≥0.3 kUA/L) to at least 1 dog or cat allergen component. There were 61.1% children sensitized to components from both sources, 29.2% - exclusively to cat, and 9.7% - to dog components. The major sensitizers were Fel d 1 (84.8%) and Can f 1 (59.4%). There were 42.9% patients sensitized to 3 or more different mammalian protein families and 40.4% - to 3 or more lipocalins. There were 5.7% of children sensitized both to Fel d 1 + Fel d 4 and Can f 1/2 + Can f 5, indicating the high risk of severe asthma. Monosensitization to Fel d 1 was the dominant pattern among Lithuanian children (26.3%). Conclusion: The majority of children were cat/dog-polysensitized, although sensitization only to cat allergens was most observed. Extensive molecular profiling can be an useful tool for accurate true sensitization diagnosis and prognosis of disease severity.

Sensitization patterns of plant panallergens in Georgian allergic population from the molecular perspective.

Introduction: In allergy diagnostics, component-resolved diagnostics (CRD) allows the clinician to assess the presence of specific IgE (sIgE) to allergenic proteins. Molecular diagnostics has improved our ability to identify not only species-specific, but also panallergen components. Aim: To characterize the Georgian allergic population according to the most frequently recognized plant panallergen components (profilins, PR-10 and nonspecific lipid transfer proteins) using sensitization data from multiplex CRD and investigate their association with particular allergic diseases. Material and methods: Patients, IgE positive to at least one studied panallergen component, were selected out of total 435 allergic individuals and stratified in two age groups: children and adults. Descriptive statistics, Chi square test (χ2) and Pearson Correlation test (r) were used for analysing the data. Results: 38% (164/435) of investigated allergic patients showed IgE reactivity to at least one molecule belonging to Profilin, PR-10 and nsLTP families. Generally, PR-10 reactive individuals represented the largest group of patients (56.0%), followed by Profilins (43.0%) and nsLTP (32.0%). For the PR-10 allergen group, IgE sensitization was dominated by Bet v 1, for Profilin - by Hev b 8 and for nsLTP - by Pru p 3. It was shown that sensitization with nsLTPs revealed statistically important associations with allergic rhinitis (p = 0.005) and dermatitis (p = 0.02). PR-10 allergen sensitization was associated with allergic rhinitis (p = 0.04) and asthma (p = 0.04). Conclusions: According to our results, sensitization to plant panallergens in the Georgian population creates characteristic features overlapping serotypes of Central Europe and Mediterranean region.

The role of basophil activation test and component-resolved diagnostics in the workup of egg allergy in children at low risk for severe allergic reactions: A real-life study.

BACKGROUND: The gold standard for diagnosing egg allergy in children is the oral food challenge (OFC). However, OFCs are time-consuming and risky procedures. Our study aimed to evaluate the utility of the basophil activation test (BAT) and component-resolved diagnostic in the diagnostic workup of children with egg allergy. METHODS: Overall, 86 children aged 6 months to 17 years, suspected of egg allergy, underwent OFC with boiled egg according to international standardized protocols. BAT and specific immunoglobulin E (sIgE) testing to component egg proteins (Gal d 1-4) were also performed. RESULTS: Of the 22 children who reacted to boiled egg, only one experienced anaphylaxis during the challenge. BAT was performed in samples obtained by 75 of the 86 patients of our cohort. Egg white and yolk protein extracts induced CD63 upregulation in the egg-allergic (EA) children compared with sensitized children that tolerated boiled egg (we registered an overall mean of CD63 expression in the EA population of 44.4% [SD 34.1] for egg white and 34.7% [SD 31.3] for egg yolk vs. 12.5% [SD 19.1] and 10.0% [SD 16.0] in sensitized children). BAT could discriminate between true egg allergy and egg sensitization in our population. As a second-line diagnostic step, the positivity of BAT for egg white or Gal d 1-sIgE resulted in a 40.9% OFC reduction, especially for those with a positive outcome. CONCLUSION: The BAT may be implemented in the diagnostic workup of egg allergy in children and, in a stepwise approach, separately or combined with Gal d 1-sIgE, may predict the allergic status and reduce the number of positive OFCs in children with egg allergy at low risk for severe reactions.

Sesame allergy in children: New insights into diagnosis and management.

Sesame is a potentially potent allergen that can trigger skin, gastrointestinal, and respiratory tract symptoms, and anaphylaxis. Only 20% to 30% of sesame-allergic children develop tolerance. The prevalence of sesame allergy depends on local diets and ranges from 0.1% to 0.9%. A high risk of accidental exposure to sesame has resulted in mandatory food labeling in many countries. More than half of patients with sesame allergy are also allergic to peanut/tree nuts. Serum-specific IgE testing with a quantitative Ses i 1 component can be performed safely and has higher clinical specificity and better positive predictive value for oral food challenge (OFC) than whole sesame extract or skin prick testing (SPT). Compared with SPT or OFC, in vitro Ses i 1 testing requires no special techniques and carries no risk of reactions. Diagnosis of suspected sesame allergy begins with a thorough history and physical examination. A positive sesame extract test (≥0.1 kUA /L) should prompt further testing. In patients with a high probability of reacting, results of component testing may facilitate a decision about performing an OFC. In a Japanese study of OFC and Ses i 1, there was a 5% probability of a positive OFC with Ses i 1 sIgE levels <0.13 kUA /L, and a 50% probability of a positive OFC with levels >32.0 kUA /L. Most patients could safely consume sesame if sIgE levels were <0.13 kUA /L. Ses i 1 testing can be used to guide appropriate management (avoidance, emergency medication, and oral immunotherapy).

Amino Acid Profiling Identifies Disease-Specific Signatures in IgE-Mediated and Non-IgE-Mediated Food Allergy in Pediatric Patients with Atopic Dermatitis.

An IgE-mediated food allergy (FA) in atopic dermatitis (AD) children should be easily differentiated from other immune-mediated adverse effects related to food. Specific IgEs for particular protein components has provided additional diagnostic value. However, component-resolved diagnostics (CRD) has not solved all diagnostic problems either. We analysed the serum profile of 42 amino acids (AAs) in 76 AD children aged 2-60 months with an IgE-mediated FA (n = 36), with a non-IgE-mediated FA (n = 15) and without an FA (n = 25) using high-performance liquid chromatography coupled with mass spectrometry (LC-MS/MS) and an aTRAQ kit. We identified homocitrulline (Hcit), sarcosine (Sar) and L-tyrosine (Tyr) as features that differentiated the studied groups (one-way ANOVA with least significant difference post hoc test). The Hcit concentrations in the non-IgE-mediated FA group were significantly decreased compared with the IgE-mediated FA group (p = 0.018) and the control group (p = 0.008). In AD children with a non-IgE-mediated FA, the Tyr levels were also significantly reduced compared with the controls (p = 0.009). The mean concentration of Sar was the highest in the non-IgE-mediated FA group and the lowest in the IgE-mediated FA group (p = 0.047). Future studies should elucidate the involvement of these AAs in the molecular pathway of IgE- and non-IgE-mediated allergic responses.

Factors predicting the outcome of allergen-specific nasal provocation test in children with grass pollen allergic rhinitis.

Background: Nasal provocation testing (NPT) is a reference methodology to identify the culprit allergen in patients with allergic rhinitis. Selecting the right allergen for NPT is particularly difficult in poly-sensitized patients with seasonal allergic rhinitis (SAR). Predictors of NPT outcomes may facilitate the proper use of this test or even substitute it. Objective: To identify predictors of grass pollen NPT outcome from an array of clinical data, e-diary outcomes, and allergy test results in poly-sensitized pediatric patients with SAR. Methods: Poly-sensitized, SAR patients with grass pollen allergy, participating in the @IT.2020 pilot project in Rome and Pordenone (Italy), participated in a baseline (T0) visit with questionnaires, skin prick testing (SPT), and blood sampling to measure total (ImmunoCAP, TFS, Sweden) and specific IgE antibodies to grass pollen extracts and their major allergenic molecules (ESEP, Euroimmun Labordiagnostika, Germany). During the pollen season, patients filled the AllergyMonitor® e-diary app measuring their symptoms, medication intake, and allergy-related well-being via the Visual Analogue Scale (VAS). After the pollen season (T1), patients answered clinical questionnaires and underwent a nasal provocation test (NPT) with grass pollen extract. Results: We recruited 72 patients (age 14.3 ± 2.8 years, 46 males) sensitized to grass and/or other pollens, including olive (63; 87.5%) and pellitory (49; 68.1%). Patients positive to grass pollen NPT (61; 84.7%), compared to the negative ones, had worse VAS values in the e-diary, larger SPT wheal reactions, and higher IgE levels, as well as specific activity to timothy and Bermuda grass extracts, rPhl p 5 and nCyn d 1. A positive NPT to grass pollen was predicted by an index combining the specific activity of IgE towards Phl p 5 and Cyn d 1 (AUC: 0.82; p < 0.01; best cut-off ≥7.25%, sensitivity 70.5%, specificity: 90.9%). VAS results also predicted NPT positivity, although with less precision (AUC: 0.77, p < 0.01; best cut-off ≥7, sensitivity: 60.7%, specificity: 81.8%). Conclusions: An index combining the specific activity of IgE to rPhl p 5 and nCyn d 1 predicted with moderate sensitivity and high specificity the outcome of a grass pollen NPT in complex, poly-sensitized pediatric patients with seasonal allergic rhinitis. Further studies are needed to improve the index sensitivity and to assess its usefulness for NPT allergen selection or as an alternative to this demanding test procedure.