The role of diagnostic tests and oral food challenge results to predict sesame allergy.

BACKGROUND: The presence of sesame allergy and its importance are increasing. OBJECTIVE: To determine the results of sesame and tahini oral food challenges (OFCs) and whether sesame-specific immunoglobulin E and skin prick tests (SPTs) accurately predicted sesame allergy in children. METHODS: Patients with suspected sesame allergy between June 1, 2018, and June 1, 2020, were examined. RESULTS: Of 92 patients (n = 65, 70.7% of the patients were boys) with a median age of 2 years (interquartile range, 1.2-3.8 years), 64 were reactive to tahini. Of 64 patients, 41 had a positive OFC result and 23 had a consistent history. Of 54 sesame OFCs, 10 patients had a positive outcome. Of 44 with a negative outcome of sesame OFC, 4 experienced allergic reactions with tahini at home and 22 patients had a positive result for tahini OFC. In multivariate logistic regression analysis, clinical reactivity of sesame (either a consistent history or a positive OFC) was positively associated with sesame SPT (odds ratio, 2.120; 95% confidence interval, 1.136-3.957; P = .01) and tahini SPT (odds ratio, 1.661; 95% confidence interval, 1.143-2.413; P = .008). Nevertheless, sesame-specific immunoglobulin E did not predict clinical reactivity. Tahini OFC outcomes were well predicted for both sesame and tahini SPTs (area under the curves of 0.937 and 0.896, respectively, P < .001 for both). A sesame SPT wheal size of 5.25 mm had 90.6% sensitivity, 82.1% specificity, and 5.1 positive likelihood ratio. For tahini SPT, the 6-mm threshold had 100% sensitivity, 82.1% specificity, and 5.6 positive likelihood ratio. CONCLUSION: In the OFC, tahini emerged as a more optimal diagnostic tool to avoid false negatives. Furthermore, both high sesame and tahini SPT levels individually can help predict the diagnosis of sesame allergy.

Oral food challenge in IgE mediated food allergy in eastern Mediterranean children.

BACKGROUND: The oral food challenge (OFC) in IgE mediated food allergy causes anxiety both in parents and in patients due to its inherent risks. OBJECTIVE: Documentation of the rate, spectrum, and predictors of positive reactions is instructive. METHODS: Children, who underwent OFC between January 1, 2017 and December 31, 2019 were analyzed. RESULTS: A total of 1361 OFCs in 613 cases were reviewed. Most of them were performed in preschool children (≤2 years 50%) and 55% of them had more than one OFC. Mainly considered food groups were cow's milk (31.8%), hen's egg (28.5%), tree nuts (20%), legumes (7%), seeds (4.9%), and wheat (2.7%). The overall OFC positivity was 9.6%, whereas 6.7% with cow's milk, 4.9% with hen's egg, 16.1% with tree nuts, 21.6% with wheat, and 32.8% with seeds. The severity scoring revealed grade I (24.4%), II (45.8%), and III (29.7%) reactions. Fifty (38%) cases required epinephrine and four cases required hospitalization. OFCs with sesame seeds (odds ratio [OR]: 7.747, [confidence interval (CI) 95%: 4.03-14.90]), wheat (OR: 3.80, [CI: 1.64-8.84]), and tree nuts (OR: 2.78, [CI: 1.83-4.23]) predicted a positive OFC while a concomitant asthma (OR: 3.61 [CI: 1.27-10.28]) was more likely to elicit anaphylaxis. CONCLUSION: In OFC practice, priority is given to basic nutritional sources and the most frequent food allergens, where preschool children with multiple sensitizations are the primary subjects. Increased risks of positive reactions with sesame, tree nut, and wheat and increased risk of anaphylaxis with concomitant asthma should be considered while performing OFC.

The mechanism of sesame resistance against Macrophomina phaseolina was revealed via a comparison of transcriptomes of resistant and susceptible sesame genotypes.

BACKGROUND: Sesame (Sesamum indicum) charcoal rot, a destructive fungal disease caused by Macrophomina phaseolina (Tassi) Goid (MP), is a great threat to the yield and quality of sesame. However, there is a lack of information about the gene-for-gene relationship between sesame and MP, and the molecular mechanism behind the interaction is not yet clear. The aim of this study was to interpret the molecular mechanism of sesame resistance against MP in disease-resistant (DR) and disease-susceptible (DS) genotypes based on transcriptomics. This is the first report of the interaction between sesame and MP using this method. RESULTS: A set of core genes that response to MP were revealed by comparative transcriptomics and they were preferentially associated with GO terms such as ribosome-related processes, fruit ripening and regulation of jasmonic acid mediated signalling pathway. It is also exhibited that translational mechanism and transcriptional mechanism could co-activate in DR so that it can initiate the immunity to MP more rapidly. According to weighted gene co-expression network analysis (WGCNA) of differentially expressed gene sets between two genotypes, we found that leucine-rich repeat receptor-like kinase (LRR-RLK) proteins may assume an important job in sesame resistance against MP. Notably, compared with DS, most key genes were induced in DR such as pattern recognition receptors (PRRs) and resistance genes, indicating that DR initiated stronger pattern-triggered immunity (PTI) and effector-triggered immunity (ETI). Finally, the study showed that JA/ET and SA signalling pathways all play an important role in sesame resistance to MP. CONCLUSIONS: The defence response to MP of sesame, a complex bioprocess involving many phytohormones and disease resistance-related genes, was illustrated at the transcriptional level in our investigation. The findings shed more light on further understanding of different responses to MP in resistant and susceptible sesame.

The importance of the 2S albumins for allergenicity and cross-reactivity of peanuts, tree nuts, and sesame seeds.

Allergies to peanuts, tree nuts, and sesame seeds are among the most important food-related causes of anaphylaxis. Important clinical questions include: Why is there a variable occurrence of coallergy among these foods and Is this immunologically mediated? The clinical and immunologic data summarized here suggest an immunologic basis for these coallergies that is based on similarities among the 2S albumins. Data from component resolved diagnostics have highlighted the relationship between IgE binding to these allergens and the presence of IgE-mediated food allergy. Furthermore, in vitro and in vivo experiments provide strong evidence that the 2S albumins are the most important allergens in peanuts for inducing an allergic effector response. Although the 2S albumins are diverse, they have a common disulfide-linked core with similar physicochemical properties that make them prime candidates to explain much of the observed coallergy among peanuts, tree nuts, and sesame seeds. The well-established frequency of cashew and pistachio nut coallergy (64%-100%) highlights how the structural similarities among their 2S albumins may account for observed clinical cross-reactivity. A complete understanding of the physicochemical properties of the 2S albumins in peanuts, tree nuts, and sesame seeds will enhance our ability to diagnose, treat, and ultimately prevent these allergies.

Milk allergy most burdensome in multi-food allergic children.

BACKGROUND: Food allergy is a substantial health burden, which disproportionately affects children. Among children with food allergy, as many as 70% have multiple food allergies. Whereas the overall burden of food allergy on quality of life has been described, little is known about the burden of individual allergens. We aimed to examine the perception of burden among families with multiple food-allergic children. METHODS: Parents of children with 1 + children with multiple food allergies including milk responded to online questions, including both open-ended and closed-ended questions on food allergy-related burdens of time, financial costs, social restrictions, and emotional demands. RESULTS: Overall, 64 children (69.8% boys) of whom (73.0%) most were aged 10 and younger were included. Most had been diagnosed with food allergy in infancy and by a (pediatric) allergist. Other common allergies included peanut (65.6%), tree nuts (57.8%), egg (76.6%), and sesame (31.3%). Quantitatively, milk allergy was reported as carrying the most burden, including most socially limiting (81.5%), requiring the most planning (75.9%), causing the most anxiety (68.5%), most challenging to find "safe" or allergy-friendly foods (72.2%), and costly (81.5%). Qualitatively, we identified five themes that captured burdens associated with costs, marketing of milk products to children, risk of cross-contamination, ubiquity of milk/dairy and public confusion with lactose intolerance, and an unwillingness of others to accommodate the allergy. CONCLUSION: Parents whose children have multiple food allergies, including milk, report milk as the allergy associated with the greatest time, financial, social, and emotional burdens.

Comparison of Diagnostic Tests with Oral Food Challenge in a Clinical Trial for Adult Patients with Sesame Anaphylaxis.

Sesame food allergy (SFA); especially anaphylaxis, is a life-threatening condition. The accurate diagnosis of SFA is done by skin prick test (SPT), skin prick to prick (SPP) or specific IgE (sIgE) and is confirmed by oral food challenge (OFC). Since there are few studies evaluating and comparing the utility of these methods for diagnosis of sesame anaphylaxis in adult patients, we aimed to compare OFC with diagnostic tests, including SPT, SPP, and sesames IgE; using ImmunoCAP considering the sensitivity and specificity issues in patients with sesame anaphylaxis. Twenty patients with sesame anaphylaxis were diagnosed based on OFC. Then SPT, SPP, and sIgE were evaluated. Sixteen patients had positive OFC; while 4 patients had negative results. Out of 16 OFC+ patients, 7 patients were SPT+, 15 patients were SPP+, and 2 patients had detectable sIgE. A positive SPT indicated 44% sensitivity and 50% specificity. A positive SPP showed 87.5% sensitivity and 75% specificity. A positive ImmunoCAP test demonstrated 12.5% sensitivity and 75% specificity. The AUC of SPP was significant for the diagnosis of sesame anaphylaxis (p=0.038). In conclusion, when the OFC is not possible, the SPP test with natural sesame seed may be applicable in patients with a convincing history instead of the artificial or commercial extracts of sesame used for SPT. Positive SPP is a good alternative diagnostic method for patients with sesame anaphylaxis. Also, the poor sensitivity of SPT and sIgE may indicate the poor discriminative capability of these tests.

Updated population minimal eliciting dose distributions for use in risk assessment of 14 priority food allergens.

Food allergy and allergen management are important global public health issues. In 2011, the first iteration of our allergen threshold database (ATDB) was established based on individual NOAELs and LOAELs from oral food challenge in roughly 1750 allergic individuals. Population minimal eliciting dose (EDp) distributions based on this dataset were published for 11 allergenic foods in 2014. Systematic data collection has continued (2011-2018) and the dataset now contains over 3400 data points. The current study provides new and updated EDp values for 14 allergenic foods and incorporates a newly developed Stacked Model Averaging statistical method for interval-censored data. ED01 and ED05 values, the doses at which 1%, and respectively 5%, of the respective allergic population would be predicted to experience any objective allergic reaction were determined. The 14 allergenic foods were cashew, celery, egg, fish, hazelnut, lupine, milk, mustard, peanut, sesame, shrimp (for crustacean shellfish), soy, walnut, and wheat. Updated ED01 estimates ranged between 0.03 mg for walnut protein and 26.2 mg for shrimp protein. ED05 estimates ranged between 0.4 mg for mustard protein and 280 mg for shrimp protein. The ED01 and ED05 values presented here are valuable in the risk assessment and subsequent risk management of allergenic foods.

Defining challenge-proven coexistent nut and sesame seed allergy: A prospective multicenter European study.

BACKGROUND: Peanut, tree nut, and sesame allergies are responsible for most life-threatening food-induced allergic reactions. Rates of coexistent allergy between these foods have been from mostly retrospective studies that include only a limited number of tree nuts or were not based on oral food challenges. OBJECTIVE: The Pronuts study is a multicenter European study (London, Geneva, and Valencia) assessing the challenge-proven rate of coexistent peanut, tree nut, and/or sesame seed allergy. METHODS: Children aged 0 to 16 years with at least 1 confirmed nut or sesame seed allergy underwent sequential diagnostic food challenges to all other nuts and sesame seed. RESULTS: Overall, the rate of coexistent peanut, tree nut, and sesame seed allergy was 60.7% (n = 74/122; 95% CI, 51.4% to 69.4%). Peanut allergy was more common in London, cashew and pistachio nut allergies were more common in Geneva, and walnut and pecan allergies were more common in Valencia. Strong correlations were found between cashew-pistachio, walnut-pecan, and walnut-pecan-hazelnut-macadamia clusters. Age (>36 months) and center (Valencia > Geneva > London) were associated with an increased odds of multiple nut allergies. By pursuing the diagnostic protocol to demonstrate tolerance to other nuts, participants were able to introduce a median of 9 nuts. CONCLUSION: We found a higher rate of coexistent nut and sesame seed allergies than previously reported. Performing sequential food challenges was labor intensive and could result in severe allergic reactions; however, it reduced dietary restrictions. Age was a significant predictor of multiple nut allergies, and thus the secondary spread of nut allergies occurred in older children.

Antibody Cross-Reactivity between Proteins of Chia Seed ( Salvia hispanica L.) and Other Food Allergens.

Chia seeds are becoming increasingly common in Europe because of their functional and nutritional properties. Despite this, few studies have focused on the allergic potential and antibody cross-reactivity among storage proteins in chia seed and other plants. The aim of this study was to identify chia seed's immunoglobulin G (IgG) and immunoglobulin E (IgE) binding proteins ( Salvia hispanica L.) and to investigate the antibody cross-reactivity among its storage proteins and those of other seeds. Extracted chia seed proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Immunodetection was performed with commercial antibodies against sesame seed, hazelnut, and peanut and sera from 33 patients with a hazelnut allergy and five with a sesame allergy. Cross-reactivity of certain antibodies with storage proteins of chia seed, sesame seed, and hazelnut was assessed using an enzyme-linked immunosorbent assay (ELISA) inhibition, blot inhibition, and surface plasmon resonance (SPR) spectroscopy. IgG binding proteins were identified at molecular weight (MW) 70, 49, 34, 23, and 20 kDa by applying commercial antibodies. Furthermore, the interaction of chia proteins with sera from sesame-allergic patients led to identify IgE binding proteins at MW 49, 45, 31, 20, and 12 kDa, while IgEs in sera from hazelnut-allergic patients reacted with proteins at MW 300, 140, 49, 45, 31, 20, and 6 kDa. The results of ELISA inhibition and blot inhibition indicated chia seed proteins are similar to sesame seed and hazelnut proteins in the primary structure. The antisesame antibodies' binding to sesame proteins was more strongly inhibited by the chia globulin fraction (GLO) than the antihazelnut antibodies' binding to hazelnut proteins. SPR results confirmed the presence of IgG binding proteins in GLO and the high similarity of epitopes on globulins of chia seed and sesame seed. Thus, chia seed consumption might lead to cross-sensitization in patients with a sesame allergy.

Demographic, Clinical, and Allergic Characteristics of Children with Eosinophilic Esophagitis in Isfahan, Iran.

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease isolated to the esophagus Food allergy is thought to play an important role in the pathophysiology of EOE. The aim of this study is to evaluate demographic features and sensitivity of patients with reference to common food allergens. Children with documented EoE were enlisted for this study. Skin prick test and patch test were done for all participants. Each test contained common food allergens. Other tests, such as evaluation of total IgE and eosinophil count, were also done. A total of 30 patients (the mean age of participants was 3±6 years) with 6 months to 15 years documented EoE participated in this study. The mean duration of symptoms was 2 years. Association with other allergic disorders was seen in 16 (32%) patients [Asthma in 8 (26.7%), allergic rhinitis in 5 (16.7%) and eczema in 3 (10%)]. The mean level of total IgE was 413.5±505.5 (IU/ML): total IgE level was above normal range for age in 17 children. The mean level of eosinophil was 372.2±305.2, and eosinophilia was seen in 11 patients (36.7%). The skin prick test and patch test findings showed that 28 patients (93%) and 17 of 30 patients (56.6%) tested positive to foods respectively. The most common positive skin prick test was for sesame and walnut. Patch test showed that the most common positive test was for fish. Evaluating the symptoms indicated that vomiting (70%) is the most prevalent symptom in patients; the less prevalent symptom was dysphagia (3.3%). Other prevalent symptoms were subsequent abdominal pain (33.3%), gaining weight failure (33.3%), heartburn (16.6%), cough (10%), fecal impaction (10%), and constipation (6.66%). Our series confirms the high degree of atopy in Iranian children with EoE. These patients seem to be polysensitized to several food allergens Because of different eating cultures in different countries, considering special food in selecting allergens for allergic tests is needed.

Biotrophy-necrotrophy switch in pathogen evoke differential response in resistant and susceptible sesame involving multiple signaling pathways at different phases.

Infection stages of charcoal rot fungus Macrophomina phaseolina in sesame revealed for the first time a transition from biotrophy via BNS (biotrophy-to-necrotrophy switch) to necrotrophy as confirmed by transcriptional studies. Microscopy using normal and GFP-expressing pathogen showed typical constricted thick intercellular bitrophic hyphae which gave rise to thin intracellular necrotrophic hyphae during BNS and this stage was delayed in a resistant host. Results also show that as the pathogen switched its strategy of infection, the host tailored its defense strategy to meet the changing situation. Less ROS accumulation, upregulation of ROS signaling genes and higher antioxidant enzyme activities post BNS resulted in resistance. There was greater accumulation of secondary metabolites and upregulation of secondary metabolite-related genes after BNS. A total of twenty genes functioning in different aspects of plant defense that were monitored over a time course during the changing infection phases showed a coordinated response. Experiments using phytohormone priming and phytohormone inhibitors showed that resistance resulted from activation of JA-ET signaling pathway. Most importantly this defense response was more prompt in the resistant than the susceptible host indicating that a resistant host makes different choices from a susceptible host during infection which ultimately influences the severity of the disease.

Food Challenge and Community-Reported Reaction Profiles in Food-Allergic Children Aged 1 and 4 Years: A Population-Based Study.

BACKGROUND: Oral food challenge is the main tool for diagnosing food allergy, but there is little data on the reaction profiles of young children undergoing challenges, nor how these reactions compare to reactions on accidental ingestion in the community. OBJECTIVES: To compare reaction profiles from food challenges and parent-reported reactions on accidental ingestion, and assess predictors of severe reactions. METHODS: HealthNuts is a longitudinal population-based cohort study of 5276 1-year-old infants. Infants underwent skin prick tests and those with identifiable wheals were offered food challenges. Food challenges were repeated at age 4 years in those with previous food allergy or reporting new food allergies. Community-reported reactions were ascertained from parent questionnaires. RESULTS: Food challenges were undertaken in 916 children at age 1 year and 357 children at age 4 years (a total of 2047 peanut, egg, or sesame challenges). Urticaria was the most common sign in positive challenges at both ages (age 1 year, 88.7%, and age 4 years, 71.2%) although angioedema was significantly more common at age 4 years (40.1%) than at age 1 year (12.9%). Anaphylaxis was equally uncommon at both ages (2.1% and 2.8% of positive challenges at ages 1 and 4 years, respectively) but more common for peanut than for egg (4.5% and 1.2% of positive challenges at ages 1 and 4 years, respectively). The patterns of presenting signs reported during community reactions were similar to those observed in formal food challenges. Serum food-specific IgE levels of 15 kU/L or more were associated with moderate to severe reactions but skin prick test was not. CONCLUSIONS: There was a shift from the most common presenting reaction of urticaria during food challenges toward more angioedema in older children. Serum food-specific IgE levels were associated with reaction severity.

Immunological Characterization of Dutch Sesame Seed-Allergic Patients.

BACKGROUND: Sesame seed is an allergen of growing importance worldwide. However, knowledge of the clinically relevant sesame allergen and its cross-reactivity with homologous allergens is limited. The aim of this study was the immunological characterization of Dutch sesame seed-allergic patients and evaluation of cross-reactivity between sesame seed, tree nut and pollen allergens using different sources of allergen extracts. METHODS: Six patients with a medical history of sesame seed allergy were included, i.e. 5 with an anaphylactic reaction and 1 with an oral allergy syndrome (OAS). The immunological background of the sesame seed and tree nut IgE sensitization was characterized with Western blotting and a basophil activation test (BAT). The major sesame allergen was identified by nanoLC-MS/MS. Cross-reactivity was measured using an immuno-inhibition assay with the Phadia ImmunoCAP system. RESULTS: Oleosin was identified as the major allergen for the 5 patients with an anaphylactic reaction to sesame seed, but no cross-reactivity between sesame and tree nut proteins was observed. For the patient with OAS, IgE specific to oleosin was not detected but cross-reactivity between sesame seed and tree nut proteins was observed. The BAT and ImmunoCAP inhibition test added value to the clinical and immunological characterization of sesame seed-sensitized patients, distinguishing relevant and non-relevant sensitizations. CONCLUSIONS: Our immunological approach enabled us to fully characterize the sensitization pattern of 6 sesame seed-allergic patients. The different protein composition of commercially available allergen extracts influences the outcomes of the immunological assays and thus also the diagnosis to a large extent.