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Food allergy (FA) is a potentially life‐threatening chronic condition that is becoming an increasing public health problem worldwide. This systematic review (SR) was carried out to inform the development of clinical recommendations on the treatment of IgE‐mediated FA with biologics and/or IT for the update of the EAACI guidelines. A SR of randomized‐controlled trials or quasi‐controlled trials was carried out. Studies were identified via comprehensive search strategies in Medline, Embase, and Cochrane Library, up to April 2022. Population: Human adults, children, and adolescents with IgE‐mediated FA. Intervention: IT and/or biologics. Comparator: Placebo or standard‐of‐care (allergen avoidance). Outcome: Efficacy (desensitization, sustained unresponsiveness (SU), remission), quality of life, and safety (systemic and local adverse reactions (AR)). The Cochrane RoB tool was used to assess the risk of bias. It was reported according to PRISMA and registered in PROSPERO CRD4202229828. After screening, 121 studies were included (111 for IT and 10 for biologics). Most studies had a high risk of bias and showed high heterogeneity in design and results. Metanalysis showed a positive effect of biologics and IT in terms of relative risk (RR) for achieving tolerance to the culprit food compared to avoidance or placebo. Omalizumab for any FA showed a RR of 2.17 [95% confidence interval: 1.22, 3.85]. For peanut allergy, oral IT (OIT) had a RR of 11.94 [1.76, 80.84] versus avoidance or placebo, sublingual IT (SLIT) had a RR of 3.00 [1.04, 8.66], and epicutaneous IT (EPIT) of 2.16 [1.56, 3.00]. OIT had a RR of 5.88 [2.27, 15.18] for cow's milk allergy, and of 3.43 [2.24, 5.27] for egg allergy. There was insufficient data on SLIT or EPIT for the treatment of egg and milk allergies. Most ARs reported were mild. For OIT the most common AR involved the gastrointestinal system and for EPIT, AR's most commonly affected the skin. There was limited data on severe or life‐threatening ARs. There was limited evidence for long term efficacy and quality of life. In conclusion, biologics and IT, alone or in combination, are effective in achieving desensitization while on active treatment but more evidence is needed on long‐term tolerance as current evidence is not of high quality. Adverse events while on therapy are generally mild to moderate but a long‐term comprehensive safety profile is missing. There is a critical need to optimize and standardize desensitization protocols and outcome measures to facilitate our understanding of the efficacy and safety as well as to allow for comparison between interventions. [ABSTRACT FROM AUTHOR]

This article explores the emergence of lupin as a potential hidden food allergen. The true prevalence of lupin allergy is currently unknown, but the Allergy-Vigilance Network® (AVN) reported 62 cases of lupin-induced anaphylaxis out of 2,708 cases of food-induced anaphylaxis from 2002 to 2020. The study found that lupin-induced anaphylaxis was more common in females, adults, individuals with a peanut allergy, and after consuming prepacked food products. The research also revealed a significant degree of cross-reactivity between lupin and other legumes, particularly peanut. The authors recommend that allergists be aware of lupin cross-reactivity and that patients with a history of food anaphylaxis be tested for lupin. [Extracted from the article]

Background: There are no studies of longitudinal immunoglobulin measurements in a population‐based cohort alongside challenge‐confirmed peanut allergy outcomes. Little is known about biomarkers for identifying naturally resolving peanut allergy during childhood. Objectives: To measure longitudinal trends in whole peanut and component Ara h 2 sIgE and sIgG4 in the first 10 years of life, in a population cohort of children with challenge‐confirmed peanut allergy, and to determine whether peanut‐specific immunoglobulin levels or trends are associated with peanut allergy persistence or resolution by 10 years of age. Methods: One‐year‐old infants with challenge‐confirmed peanut allergy (n = 156) from the HealthNuts study (n = 5276) were prospectively followed at ages 4, 6, and 10 years with questionnaires, skin prick tests, oral food challenges, and plasma total‐IgE, sIgE and sIgG4 to peanut and Ara h 2. Results: Peanut allergy resolved in 33.9% (95% CI = 25.3%, 43.3%) of children by 10 years old with most resolving (97.4%, 95% CI = 86.5%, 99.9%) by 6 years old. Decreasing Ara h 2 sIgE (p =.01) and increasing peanut sIgG4 (p <.001), Ara h 2 sIgG4 (p =.01), peanut sIgG4/sIgE (p <.001) and Ara h 2 sIgG4/sIgE (p <.001) from 1 to 10 years of age were associated with peanut allergy resolution. Peanut sIgE measured at 1 year old had the greatest prognostic value (AUC = 0.75 [95% CI = 0.66, 0.82]); however, no single threshold produced both high sensitivity and specificity. Conclusion: One third of infant peanut allergy resolved by 10 years of age. Decreasing sIgE and sIgG4 to peanut and Ara h 2 over time were associated with natural resolution of peanut allergy. However, biomarker levels at diagnosis were not strongly associated with the natural history of peanut allergy. [ABSTRACT FROM AUTHOR]

Type 2 allergen‐specific T cells are essential for the induction and maintenance of allergies to foods, and Tregs specific for these allergens are assumed to be involved in their resolution. However, it has not been convincingly demonstrated whether allergen‐specific Treg responses are responsible for the generation of oral tolerance in humans. We observed that sustained food allergen exposure in the form of oral immunotherapy resulted in increased frequency of Tregs only in individuals with lasting clinical tolerance. We sought to identify regulatory components of the CD4+ T‐cell response to food allergens by studying their functional activation over time in vitro and in vivo. Two subsets of Tregs expressing CD137 or CD25/OX40 were identified with a delayed kinetics of activation compared with clonally enriched pathogenic effector Th2 cells. Treg activation was dependent on IL‐2 derived from effector T cells. In vivo exposure to peanut in the form of an oral food challenge of allergic subjects induced a delayed and persistent activation of Tregs after initiation of the allergen‐specific Th2 response. The novel finding of our work is that a sustained wave of Treg activation is induced by the release of IL‐2 from Th2 effector cells, with the implication that therapeutic administration of IL‐2 could improve current OIT approaches. [ABSTRACT FROM AUTHOR]

Background: There is substantial interest in immunotherapy and biologicals in IgE‐mediated food allergy. Methods: We searched six databases for randomized controlled trials about immunotherapy alone or with biologicals (to April 2021) or biological monotherapy (to September 2021) in food allergy confirmed by oral food challenge. We pooled the data using random‐effects meta‐analysis. Results: We included 36 trials about immunotherapy with 2126 mainly child participants. Oral immunotherapy increased tolerance whilst on therapy for peanut (RR 9.9, 95% CI 4.5.–21.4, high certainty); cow's milk (RR 5.7, 1.9–16.7, moderate certainty) and hen's egg allergy (RR 8.9, 4.4–18, moderate certainty). The number needed to treat to increase tolerance to a single dose of 300 mg or 1000 mg peanut protein was 2. Oral immunotherapy did not increase adverse reactions (RR 1.1, 1.0–1.2, low certainty) or severe reactions in peanut allergy (RR 1,6, 0.7–3.5, low certainty), but may increase (mild) adverse reactions in cow's milk (RR 3.9, 2.1–7.5, low certainty) and hen's egg allergy (RR 7.0, 2.4–19.8, moderate certainty). Epicutaneous immunotherapy increased tolerance whilst on therapy for peanut (RR 2.6, 1.8–3.8, moderate certainty). Results were unclear for other allergies and administration routes. There were too few trials of biologicals alone (3) or with immunotherapy (1) to draw conclusions. Conclusions: Oral immunotherapy improves tolerance whilst on therapy and is probably safe in peanut, cow's milk and hen's egg allergy. More research is needed about quality of life, cost and biologicals. [ABSTRACT FROM AUTHOR]

Background: Food allergen immunotherapy (FA‐AIT) practice is known to vary globally. This project aims to identify and characterize European centres performing FA‐AIT. Methods: An EAACI task force conducted an online survey to gather relevant information regarding FA‐AIT practice and setting‐specific resources after reviewing the published literature and congress abstracts throughout Europe. Results: We identified 102 FA‐AIT centres in 18 countries; only Spain (n = 39) and France (n = 16) had ≥10 such centres. Overall, most facilities were hospital‐based (77.5%), publicly funded (80.4%) and delivered FA‐AIT as routine clinical care (80.4%). On average, departments had 3 allergists/paediatric allergists and 2 nurses. Surveyed centres had provided FA‐AIT for a median of 9 years [1–24] to a median of 105 [5–2415] patients. The estimated total number of treated patients was 24875, of whom 41.3% received AIT for milk, 34.2% egg, 12.8% peanut and 11.7% other foods. Anaphylaxis to AIT doses requiring over 4–6 h of observation was reported by 70.6% of centres, ICU admissions by 10.8% and eosinophilic esophagitis by 45.1%. Quality of life and sustained unresponsiveness were evaluated in 20.6% and 54.9% of centres, respectively. The main contraindications for food AIT were severe asthma (57%‐63%), eosinophilic esophagitis (56%‐48%) and age below 5 years (47%‐41%). Conclusions: In Europe, FA‐AIT is provided mostly in clinical practice. Significant variation is seen in the number of centres per country, facility characteristics and inclusion/exclusion criteria, and in certain aspects of protocols. Potential inequality in access to AIT has been identified as well as the need for education and guidance for treatment standardization. [ABSTRACT FROM AUTHOR]

Background: Accurate diagnosis of peanut allergy is a significant clinical challenge. Here, a novel diagnostic blood test using the peanut bead‐based epitope assay ("peanut BBEA") was developed utilizing the LEAP cohort and then validated using two independent cohorts. Methods: The development of the peanut BBEA diagnostic test followed the National Academy of Medicine's established guidelines with discovery performed on 133 subjects from the non‐interventional arm of the LEAP trial and an independent validation performed on 82 subjects from the CoFAR2 and 84 subjects from the POISED study. All samples were analyzed using the peanut BBEA methodology, which measures levels of IgE to two Ara h 2 sequential (linear) epitopes and compares their combination to a threshold pre‐specified in the model development phase. When a patient has an inconclusive outcome by skin prick testing (or sIgE), IgE antibody levels to this combination of two epitopes can distinguish whether the patient is "Allergic" or "Not Allergic." Diagnoses of peanut allergy in all subjects were confirmed by double‐blind placebo‐controlled food challenge and subjects' ages were 7–55 years. Results: In the validation using CoFAR2 and POISED cohorts, the peanut BBEA diagnostic test correctly diagnosed 93% of the subjects, with a sensitivity of 92%, specificity of 94%, a positive predictive value of 91%, and negative predictive value of 95%. Conclusions: In validation of the peanut BBEA diagnostic test, the overall accuracy was found to be superior to existing diagnostic tests for peanut allergy including skin prick testing, peanut sIgE, and peanut component sIgE testing. [ABSTRACT FROM AUTHOR]

Background: There are no studies of longitudinal immunoglobulin measurements in a population-based cohort alongside challenge-confirmed peanut allergy outcomes. Little is known about biomarkers for identifying naturally resolving peanut allergy during childhood., Objectives: To measure longitudinal trends in whole peanut and component Ara h 2 sIgE and sIgG 4 in the first 10 years of life, in a population cohort of children with challenge-confirmed peanut allergy, and to determine whether peanut-specific immunoglobulin levels or trends are associated with peanut allergy persistence or resolution by 10 years of age., Methods: One-year-old infants with challenge-confirmed peanut allergy (n = 156) from the HealthNuts study (n = 5276) were prospectively followed at ages 4, 6, and 10 years with questionnaires, skin prick tests, oral food challenges, and plasma total-IgE, sIgE and sIgG 4 to peanut and Ara h 2., Results: Peanut allergy resolved in 33.9% (95% CI = 25.3%, 43.3%) of children by 10 years old with most resolving (97.4%, 95% CI = 86.5%, 99.9%) by 6 years old. Decreasing Ara h 2 sIgE (p = .01) and increasing peanut sIgG 4 (p < .001), Ara h 2 sIgG 4 (p = .01), peanut sIgG 4 /sIgE (p < .001) and Ara h 2 sIgG 4 /sIgE (p < .001) from 1 to 10 years of age were associated with peanut allergy resolution. Peanut sIgE measured at 1 year old had the greatest prognostic value (AUC = 0.75 [95% CI = 0.66, 0.82]); however, no single threshold produced both high sensitivity and specificity., Conclusion: One third of infant peanut allergy resolved by 10 years of age. Decreasing sIgE and sIgG 4 to peanut and Ara h 2 over time were associated with natural resolution of peanut allergy. However, biomarker levels at diagnosis were not strongly associated with the natural history of peanut allergy., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background Allergy can be diagnosed using basophil tests. Several methods measuring basophil activation are available. This study aimed at comparing basophil activation test ( BAT), histamine release assay ( HR), and passive sensitization histamine release assay (passive HR) in the diagnosis of peanut allergy. Methods BAT, HR, and passive HR were performed on 11 peanut-allergic and 14 nonallergic subjects. Blood was incubated with peanut extract or anti-IgE and tests were performed as follows: BAT- CD63 upregulation was assessed by flow cytometry; HR-released histamine was quantified by a glass fiber-based fluorometric method; passive HR-IgE-stripped donor basophils were incubated with participants' serum and histamine release was quantified as HR. Results CDsens, a measure of basophil allergen sensitivity, was significantly higher for BAT (80.1±17.4) compared to HR (23.4±10.31) and passive HR (11.1±2.0). BAT, HR, and passive HR had a clinical sensitivity of 100%, 100%, and 82% and specificity of 100%, 100%, and 100%, respectively, when excluding inconclusive results. BAT identified 11 of 11 allergic patients, HR 10, and passive HR 9. Likewise, BAT recognized 12 of 14 nonallergic subjects, HR 10, and passive HR 13. However, the tests' diagnostic performances were not statistically different. Interestingly, nonreleasers in HR but not in BAT had lower basophil count compared to releasers (249 vs 630 counts/min). Conclusion BAT displayed a significantly higher CDsens compared to HR and passive HR. The basophil tests' diagnostic performances were not significantly different. Still, BAT could diagnose subjects with low basophil number in contrast to HR. [ABSTRACT FROM AUTHOR]

Peanut ( PN) and tree nuts ( TNs) are common causes of anaphylaxis in Western countries, but no information is available in Korea. To feature clinical characteristics of anaphylaxis caused by PN, TNs, and seeds, a retrospective medical record review was performed in 14 university hospitals in Korea (2009-2013). One hundred and twenty-six cases were identified, with the mean age of 4.9 years. PN, walnut ( WN), and pine nut accounted for 32.5%, 41.3%, and 7.1%, respectively. The median values of specific IgE ( sIgE) to PN, WN, and pine nut were 10.50, 8.74, and 4.61 kUA/l, respectively. Among 50 cases managed in the emergency department, 52.0% were treated with epinephrine, 66.0% with steroid, 94.0% with antihistamines, 36.0% with oxygen, and 48.0% with bronchodilator. In conclusion, WN, PN, and pine nut were the three most common triggers of anaphylaxis in Korean children, and anaphylaxis could occur at remarkably low levels of sIgE. [ABSTRACT FROM AUTHOR]

Background DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin) is a C-type lectin receptor expressed on macrophages and dendritic cells. DC-SIGN has high affinity for fucosylated glycans in several plant glycoproteins and pathogens. DC-SIGN is thought to be crucial for the development of allergic sensitization. However, the precise role of DC-SIGN in food allergy pathogenesis is not yet understood. Objective We sought to characterize DC-SIGN-binding glycoproteins in a panel of allergenic and non-allergenic foods. Methods Fluorescent-labeled peanut and soy extracts were used to test protein binding to human monocyte-derived dendritic cells (DCs) by flow cytometry. DC-SIGN-blocking assays were performed by incubating DCs with food extracts followed by staining with anti-DC-SIGN antibody. Using a DC-SIGN-Fc chimera, food extracts were tested for binding by ELISA and autoradiography. IgE immunoblotting was performed with pooled sera from food-allergic subjects. DC activation and maturation were assessed by flow cytometry. Results and Conclusions We demonstrate that peanut agglutinin, a minor peanut allergen, is a novel ligand for DC-SIGN. Peanut agglutinin activates DCs to induce the expression of costimulatory molecules in vitro. We present a comprehensive report on the characterization of DC-SIGN-binding proteins in common allergenic foods such as peanut, soy, tree nuts, egg, and milk. Foods that rarely induce allergy, such as pine nuts, chickpea, and corn, showed no binding to DC-SIGN. Several DC-SIGN-binding proteins show reactivity in serum IgE immunoblots. We have also identified novel non-IgE-binding proteins that interact with DC-SIGN; these proteins may be important for regulating immune responses to these foods. [ABSTRACT FROM AUTHOR]

Background In Africa, peanuts are frequently consumed, but severe allergic reactions are rare. We investigated immunological patterns of clinical tolerance to peanut in peanut-sensitized but asymptomatic patients from central Africa compared to peanut-allergic and peanut-sensitized but asymptomatic patients from Sweden. Methods Sera from allergic patients ( n = 54) from Zimbabwe sensitized to peanut but without allergic symptoms to peanut, and sera from peanut-allergic ( n = 25) and peanut-sensitized but asymptomatic ( n = 25) patients from Sweden were analyzed toward peanut allergen components (Ara h 1-3, 6, 8-9) and other allergen molecules from important allergen sources using microarray. IgE to Ara h 2 peptide epitopes was analyzed, and allergenic activity was assessed by basophil activation assay. Results Forty-six percent of the African and all peanut-allergic Swedish patients showed IgE toward one of the highly allergenic peanut allergens (Ara h 1-3, 6, 9). However, 48% of the African patients had IgE to cross-reactive carbohydrate determinants ( CCDs) with low allergenic activity and 60% of the Swedish asymptomatic patients had IgE against the PR protein Ara h 8. IgG and IgG4 specificities and levels could not discriminate between the African asymptomatic and Swedish peanut-allergic patients. Asymptomatic patients almost lacked IgE to Ara h 2 peptides, which were recognized by peanut-allergic patients. Peanut IgE from peanut asymptomatic patients showed poor allergenic activity compared with IgE from peanut-allergic patients. Conclusions Natural clinical tolerance to peanut in the African patients can be caused by IgE to low allergenic peanut components and by poor allergenic activity of peanut-specific IgE. [ABSTRACT FROM AUTHOR]

Background: We tested the hypothesis that specific molecular sensitization patterns correlate with the clinical data/manifestation in a European peanut-allergic population characterized under a common protocol. Methods: Sixty-eight peanut-allergic subjects and 82 tolerant controls from 11 European countries were included. Allergy to peanut and lowest symptom-eliciting dose was established by double-blind placebo-controlled food challenge in all but anaphylactic subjects. Information of early or late (before or after 14 years of age) onset of peanut allergy was obtained from standardized questionnaires. IgE to peanut allergens rAra h 1-3, 6, 8-9, profilin and CCD was determined using ImmunoCAP. Results: Seventy-eight percent of peanut allergics were sensitized to peanut extract and 90% to at least one peanut component. rAra h 2 was the sole major allergen for the peanut-allergic population. Geographical differences were observed for rAra h 8 and rAra h 9, which were major allergens for central/western and southern Europeans, respectively. Sensitization to rAra h 1 and 2 was exclusively observed in early-onset peanut allergy. Peanut-tolerant subjects were frequently sensitized to rAra h 8 or 9 but not to storage proteins. Sensitization to Ara h 2 ≥ 1.0 kUA/l conferred a 97% probability for a systemic reaction (P = 0.0002). Logistic regression revealed a significant influence of peanut extract sensitization and region on the occurrence of systemic reactions (P = 0.0185 and P = 0.0436, respectively). Conclusion: Sensitization to Ara h 1, 2 and 3 is usually acquired in childhood. IgE to Ara h 2 ≥ 1.0 kUA/l is significantly associated with the development of systemic reactions to peanut. [ABSTRACT FROM AUTHOR]

Cashew-allergic mice develop elevated walnut-specific Ig E upon oral feeding of walnut proteins. Ingestion of tree nuts in the presence of a known nut allergy could lead to additional sensitizations and anaphylaxis following subsequent exposure. [ABSTRACT FROM AUTHOR]

Background Oral challenges are the gold standard in food allergy diagnostic, but time-consuming. Aim of the study was to investigate the role of peanut- and hazelnut-component-specific Ig E in the diagnostics of peanut and hazelnut allergy and to identify cutoff levels to make some challenges superfluous. Methods In a prospective and multicenter study, children with suspected peanut or hazelnut allergy underwent oral challenges. Specific Ig E to peanut, hazelnut, and their components ( Ara h 1, Ara h 2, Ara h 3, and Ara h 8, Cor a 1, Cor a 8, Cor a 9, and Cor a 14) were determined by Immuno CAP- FEIA. Results A total of 210 children were challenged orally with peanut and 143 with hazelnut. 43% of the patients had a positive peanut and 31% a positive hazelnut challenge. With an area under the curve of 0.92 and 0.89, respectively, Ara h 2 and Cor a 14-specific Ig E discriminated between allergic and tolerant children better than peanut- or hazelnut-specific Ig E. For the first time, probability curves for peanut and hazelnut components have been calculated. A 90% probability for a positive peanut or hazelnut challenge was estimated for Ara h 2-specific Ig E at 14.4 kU/l and for Cor a 14-specific Ig E at 47.8 kU/l. A 95% probability could only be estimated for Ara h 2 at 42.2 kU/l. Conclusions Ara h 2- and Cor a 14-specific Ig E are useful to estimate the probability for a positive challenge outcome in the diagnostic work-up of peanut or hazelnut allergy making some food challenges superfluous. [ABSTRACT FROM AUTHOR]

Ara h 1, Ara h 2, and Ara h 3 are important sensitizers in peanut allergy. Ara h 9 has also been shown to be relevant in the Mediterranean area. We evaluated the basophil response to peanut allergens and Pru p 3 in Mediterranean patients: Group 1, peanut and peach allergy; Group 2, peanut allergy and tolerance to peach; Group 3, peach allergy and tolerance to peanut; Group 4, nonallergic subjects that tolerate both peanut and peach. Compared to controls (Group 4), there was an increased basophil activation with Ara h 2 ( P = 0.031) and Pru p 3 ( P = 0.009) in Group 1 and with Ara h 1 ( P = 0.016), Ara h 2 ( P = 0.001), and Ara h 9 ( P = 0.016) in Group 2. Importantly, only Ara h 2 showed an increased activation ( P = 0.009) in Group 2 compared to Group 3. Ara h 2 is the best discriminating allergen for peanut allergy diagnosis in a Mediterranean population showing two patterns: patients also allergic to peach, responding to Ara h 2 and Pru p 3, and patients allergic only to peanut, responding to Ara h 1, Ara h 2, and Ara h 9. [ABSTRACT FROM AUTHOR]

Background Sedation might improve tolerability and adherence to endoscopic procedures in patients with eosinophilic esophagitis ( Eo E). Propofol administration is often contraindicated in patients with hypersensitivity to egg, soy, or peanut. Objective To investigate the safety of propofol administration for procedural sedation in Eo E patients sensitized/allergic to egg, soy, peanut. Methods A retrospective observational study in adult Eo E patients undergoing esophagogastroduodenoscopy with propofol sedation was conducted between January 2009 and March 2013. Food-specific serum Ig E and skin prick tests for egg, soy, peanut, and cross-reactant foods were performed in all patients. Results Sixty Eo E adult patients, mostly on food elimination diets (91%), were evaluated (age: 28 years (14-56), male gender (90%)). Atopy was present in 88% of patients, being the most prevalent comorbidities rhinoconjunctivitis (78%) and asthma (67%). Fifty-two patients (86%) were sensitized to either egg, soy, or peanut. Eighteen patients (28%) had a history of allergic reactions to egg, legumes, and nuts and strictly avoided these foods. A total of 404 upper endoscopies were performed under propofol sedation. No allergic adverse events were reported, except a transient bronchospasm after orotracheal intubation in an asthmatic adolescent receiving multiple drugs for anesthesia, in whom no sensitization to either propofol or its lipid vehicle was confirmed. Conclusions Propofol was safely administered for procedural sedation in a large series of adult Eo E patients multisensitized to egg, soy, peanut, showing one-third clinical allergy to these foods. [ABSTRACT FROM AUTHOR]

Introduction As replacement for the oral food challenge, decision-points for sensitization test have been established, but suboptimal sensitivity and/or specificity, as well as regional differences, have reduced the clinical usability. IgE toward specific peanut protein components has been reported to be of value, but data on correlation with clinical data are sparse. Our aim was to correlate IgE values with the outcome of peanut challenges. Method Data from 175 positive and 30 negative peanut challenges in patients aged 1-26 years were retrospectively correlated with the levels of specific IgE to peanut and peanut components (Ara h 1-3, h 8, and h 9). Result The best correlation between IgE and clinical thresholds was found for Ara h 2 (ρs = −0.30, P < 0.01). A cutoff of Ara h 2 > 1.63 kU/l yielded a specificity = 1.00, with a corresponding sensitivity of 0.70. Symptom severity elicited during challenge correlated significantly with the levels of Ara h 2 (ρs = 0.60, P < 0.0001), but large individual variation was found. Conclusion The level of IgE toward Ara h 2 can improve diagnostic accuracy by introducing a more clear-cut decision-point with an optimal specificity maintaining a high sensitivity. In our study, this would have reduced the necessary number of challenges to be performed from 205 to 92. Extrapolation between centers is difficult and decision-points need to be addressed in relation to settings and population. Further component-resolved diagnostic cannot replace oral challenge neither in determining thresholds nor in the assessment of severity of symptoms elicited during challenge. [ABSTRACT FROM AUTHOR]

Background: Peanut allergy affects 1% of the population and causes the most fatal food-related anaphylactic reactions. The protein Ara h 2 is the most potent peanut allergen recognized by 80–90% of peanut allergic patients. Methods: The crystal structure of the major peanut allergen Ara h 2 was determined for the first time at 2.7 A ˚ resolution using a customized maltose-binding protein (MBP)-fusion system. IgE antibody binding to the MBP fusion construct vs the natural allergen was compared by ELISA using sera from peanut allergic patients. Results: The structure of Ara h 2 is a five-helix bundle held together by four disulfide bonds and related to the prolamin protein superfamily. The fold is most similar to other amylase and trypsin inhibitors. The MBP–Ara h 2 fusion construct was positively recognized by IgE from 76% of allergic patients (25/33). Two populations of patients could be identified. Subpopulation 1 (n = 14) showed an excellent correlation of IgE antibody binding to natural vs recombinant Ara h 2. Subpopulation 2 (n = 15) showed significantly reduced IgE binding to the MBP fusion protein. Interestingly, about 20% of the IgE binding in subpopulation 2 could be recovered by increasing the distance between MBP and Ara h 2 in a second construct. Discussion: The reduced IgE binding to the MBP–Ara h 2 of subpopulation 2 indicates that the MBP molecule protects an immunodominant epitope region near the first helix of Ara h 2. Residues involved in the epitope(s) are suggested by the crystal structure. The MBP–Ara h 2 fusion constructs will be useful to further elucidate the relevance of certain epitopes to peanut allergy. [ABSTRACT FROM AUTHOR]

To cite this article: Asarnoj A, Movérare R, Östblom E, Poorafshar M, Lilja G, Hedlin G, van Hage M, Ahlstedt S, Wickman M. IgE to peanut allergen components: relation to peanut symptoms and pollen sensitization in 8-year-olds. Allergy 2010; 65: 1189–1195. Background: Allergen-specific IgE testing is often performed with crude peanut extract, but the results may be difficult to interpret because of cross-reactions between peanut and other plant allergens. The aim was to investigate IgE reactivity to peanut allergen components in children from a birch-rich region in relation to pollen sensitization and peanut symptoms. Methods: From a birth cohort, clinical parameters were obtained through questionnaires and IgE antibody levels to peanut and birch pollen were measured. Different peanut/birch sensitization phenotypes were defined among 200 selected children. IgE reactivity to peanut and pollen allergen components was analysed using microarray technique. Results: Peanut symptoms were reported in 87% of the children with IgE reactivity to any of the peanut allergens Ara h 1, 2 or 3 but not to Ara h 8 ( n = 46) vs 17% of children with IgE reactivity to Ara h 8 but not to Ara h 1, 2 or 3 ( n = 23), P < 0.001. Furthermore, symptoms were more severe in children with Ara h 1, 2 or 3 reactivity. Children with IgE reactivity both to Ara h 2 and to Ara h 1 or 3 more often reported peanut symptoms than children with IgE only to Ara h 2 (97% vs 70%, P = 0.016), particularly respiratory symptoms (50% vs 9%, P = 0.002). Conclusions: IgE analysis to peanut allergen components may be used to distinguish between peanut-sensitized individuals at risk of severe symptoms and those likely to have milder or no symptoms to peanut if sensitized to pollen allergens and their peanut homologue allergens. [ABSTRACT FROM AUTHOR]

To cite this article: Asarnoj A, Östblom E, Ahlstedt S, Hedlin G, Lilja G, van Hage M, Wickman M. Reported symptoms to peanut between 4 and 8 years among children sensitized to peanut and birch pollen – results from the BAMSE birth cohort. Allergy 2010; 65: 213–219. Background: Specific IgE tests are sometimes difficult to interpret due to structural similarities between certain food and pollen allergens. This may be the reason why concomitant sensitization to peanut and birch pollen is frequently seen. The aim of this study was to investigate reported symptoms to peanut- and birch pollen in relation to sensitization. Methods: The data originate from 1928 children in the BAMSE birth cohort. Background factors and clinical parameters were obtained and the levels of IgE antibodies to peanut and birch pollen measured at 4 and 8 years. Results: IgE antibodies to peanut were found in 5.5% and 7.4% of the children at 4 and 8 years, respectively. The IgE antibody levels to peanut were higher in children sensitized to peanut but not birch than in children sensitized to peanut and birch among both 4- and 8-year-olds ( P = 0.093 and P = 0.003, respectively). Eight-year-olds sensitized to peanut but not birch, more often reported symptoms to peanut than children sensitized to both peanut and birch pollen (76% vs 46%, P = 0.002). The probability of reported symptoms to peanut increased significantly with increasing IgE levels to peanut, especially in 8-year-olds not sensitized to birch. Conclusions: Children sensitized to both peanut and birch pollen are less likely to report symptoms to peanut than children sensitized to peanut but not to birch pollen at 8 years. This is likely due to cross reactions between birch pollen and peanut and can explain the high sensitization rate to peanut in areas where birch trees are common. [ABSTRACT FROM AUTHOR]

Background: The use of lupine in food has been increasing during the last decade and allergic reactions to lupine have been reported, especially in peanut-allergic patients. The frequency and the degree of cross-reactivity to other legumes are not known. The aim of the study was to investigate the frequency of sensitization to lupine, and in addition to pea and soy, and its clinical relevance, in peanut-sensitized patients. Furthermore, to determine the eliciting dose (ED) for lupine using double-blind placebo-controlled food challenges (DBPCFC). Methods: Thirty-nine unselected peanut-sensitized patients were evaluated by skin prick tests (SPT) and ImmunoCAP to lupine, pea, and soy. Clinical reactivity was measured by DBPCFC for lupine, and by history for pea and soy. Results: Eighty-two percent of the study population was sensitized to lupine, 55% to pea, and 87% to soy. Clinically relevant sensitization to lupine, pea, or soy occurred in 35%, 29%, and 33% respectively of the study population. None of the patients was aware of the use of lupine in food. The lowest ED for lupine, inducing mild subjective symptoms, was 0.5 mg, and the no observed adverse effect level (NOAEL) was 0.1 mg. No predictive factors for lupine allergy were found. Conclusion: In peanut-sensitized patients, clinically relevant sensitization to either lupine or to pea or soy occurs frequently. The ED for lupine is low (0.5 mg), which is only fivefold higher than for peanut. Patients are not aware of lupine allergy and the presence of lupine in food, indicating that education is important to build awareness. [ABSTRACT FROM AUTHOR]

Background: Cashew nut allergy is becoming common, but the risk of severe reactions in comparison with peanut allergy is unknown. Method: A case-matching study of children with a recent history of a reaction after definite nut ingestion, with positive skin prick test. Children whose worst ever reaction was to cashew nut (cashew group), were matched with two children each whose worst ever reaction was to peanut (peanut group) for sex, age of reaction and presentation, amount ingested, and asthma. Severity of the worst clinical reactions to date was compared. Results: A total of 47 children in the cashew group were matched to 94 in the peanut group. There were no differences in clinical features between groups for matching criteria, except asthma (more prevalent in the peanut group). Wheezing and cardiovascular symptoms were reported more frequently during reactions in the cashew compared with the peanut group: odds ratios (OR) 8.4 (95% CI: 3.2–22.0) and 13.6 (95% CI: 5.6–32.8), respectively. The cashew group received intramuscular adrenaline more frequently: OR 13.3 (95% CI: 5.5–32.2). Overall, the OR for a severe reaction (severe dyspnoea and/or collapse) in the cashew group was 25.1 (95% CI: 3.1–203.5). Conclusions: Previous studies show cashew nut can cause severe reactions; this is the first study to show by case-matching that severe clinical reactions occur more frequently in cashew compared with peanut allergy. The nut type which caused the worst reaction to date should be considered when providing emergency medication. [ABSTRACT FROM AUTHOR]

Keywords: allergens; food allergy; IgE; IgG4; peanut EN allergens food allergy IgE IgG4 peanut 1835 1836 2 07/14/20 20200701 NES 200701 To the Editor, Mose et al1 reopened the discussion on bioavailability of digestion-stable food allergens in human. Their paper elegantly shows that peanut allergen can be detected in serum, minutes to hours following peanut consumption by healthy subjects. [Extracted from the article]

The development of safe and effective immunotherapy for peanut allergy has been complicated by the high anaphylactic potential of native peanut extracts. We sought to map the T-cell epitopes of the major peanut allergen, Ara h 2 in order to develop T-cell targeted vaccines.A panel of eight peanut-specific CD4+ T-cell lines (TCL) was derived from eight peanut-allergic subjects and proliferative and cytokine responses to stimulation with a set of overlapping 20-mer peptides representing the entire sequence of Ara h 2 determined. Proliferation was assessed in 72 h assays via tritiated thymidine incorporation, while interleukin (IL)-5 and interferon (IFN)-γ production were assessed via sandwich enzyme-linked immunosorbent assay (ELISA) of cell culture supernatants.Eight of the 17 Ara h 2 peptides were recognized by one or more subjects, with the two peptides showing highest reactivity [Ara h 2 (19–38) and Ara h 2 (73–92)] being recognized by three subjects each. Adjoining peptides Ara h 2 (28–47) and Ara h 2 (100–119) induced proliferative responses in two subjects. Each of these peptides was associated with a Th2-type cytokine response.Two highly immunogenic T-cell reactive regions of Ara h 2 have been identified, Ara h 2 (19–47) and Ara h 2 (73–119), providing scope for the development of safe forms of immunotherapy for peanut allergy. [ABSTRACT FROM AUTHOR]

In a double-blind placebo-controlled food challenge (DBPCFC), it is necessary that recipes comprising the allergen cannot be distinguished from placebo. We investigated whether the method of paired comparisons, a sensory difference test, could be used to test the suitability of recipes for a DBPCFC. We used two recipes, each with three concentrations of peanut or hazelnut flour. The recipe for peanut consisted of mashed potatoes with 2.7, 8.9, or 26.8 mg of peanut flour, and the recipe for hazelnut of oatmeal porridge with 74, 247, or 742 mg of hazelnut flour. Corresponding amounts of protein in the provided 15 g portions of each recipe were 0.7, 2.3, and 6.8 mg for peanut, and 11.6, 39, and 117 mg for hazelnut, respectively. Recipes were offered together with a placebo, and evaluated on sensory features by 81 healthy volunteers. The sensory test was easy to perform. Volunteers were not able to detect peanut flour in mashed potatoes, but they recognized hazelnut flour in oatmeal porridge on visual features. Sensory testing by means of the method of paired comparisons is a useful method to evaluate masking of foods for DBPCFC. [ABSTRACT FROM AUTHOR]

Background: The aim of this paper was to investigate whether a statistical model could be developed to estimate a “threshold” dose for foods eliciting allergic reactions in susceptible patients. The threshold dose is defined to be one that elicits allergic reactions in a given (small) proportion of susceptible patients, using data from published studies. Methods: Based on data available from the literature, we developed a statistical model using the actual allergen content in the four foods, where data for allergen content are available (peanut, soy, egg, milk). Results: The model demonstrated that the threshold doses giving a reaction of one in a million in susceptible patients were within the same order of magnitude for egg, milk and soy, but were an order of magnitude lower for peanut flour: 0.005 mg of cow's milk, 0.002 mg of fresh hen's egg, 0.0007 mg of peanut, or 0.0013 mg of soy flour. Conclusions: Although several assumptions were made in creating this statistical model, we demonstrated that the previously published differences in threshold doses for various foods can be largely eliminated by comparing actual allergen content; this may therefore serve as a model for further studies. Background: The aim of this paper was to investigate whether a statistical model could be developed to estimate a “threshold” dose for foods eliciting allergic reactions in susceptible patients. The threshold dose is defined to be one that elicits allergic reactions in a given (small) proportion of susceptible patients, using data from published studies. Methods: Based on data available form the literature, we developed a statistical model using the actual allergen content in the four foods, where data for allergen content are available (peanut, soy, egg, milk). Results: The model demonstrated that the threshold doses giving a reaction of one in a million in susceptible patients were within the same order of magnitude for egg, milk and soy, but... [ABSTRACT FROM AUTHOR]

Background: Several associations have been described between tree and plant pollens and certain foods. The objective of this study is to verify whether there is cross-reactivity between Platanus pollen and vegetable origin foods. Methods: We selected 56 patients allergic to vegetable foods and subjected them to cutaneous tests with aeroallergens and vegetable foods. A statistical analysis was performed to evaluate the association of Platanus pollen with foods and with other aeroallergens. Later, a specific IgE determination was performed as well as a RAST (radioallergosorbent) inhibition experiment, to verify the existence of cross-reactivity in vitro. Results: In the cutaneous tests we found a positive correlation between Platanus pollen and hazelnut, peanut, banana and celery. The results of the RAST inhibition experiment indicate an important cross-reactivity between the pollen of Platanus acerifolia and hazelnut and banana fruit, and an intermediate cross-reactivity with celery and peanut. Conclusion: We have described an association between the pollen of the Platanus tree and some vegetable foods such as hazelnut, banana, peanut and celery. This association could be explained by the in vitro IgE cross-reactivity detected. [ABSTRACT FROM AUTHOR]

Background: Sensitization to peanut has seldom been investigated in Sweden. Therefore, all IgE-specific tests for peanut during a 5-year period were reviewed to study the relation between the levels of specific IgE antibody to peanut and age, sex, symptoms, and other atopic manifestations. Methods: All serum samples were analyzed for IgE antibodies to peanut in relation to sex, age, clinical reactions, and other food allergens. A subgroup was asked to answer a questionnaire about symptoms and atopic manifestations in relation to IgE antibody levels. Results: During the study period, 2417 tests were made for peanut. There was an increased prevalence of detectable IgE antibodies during the years studied. More than 80 individuals under 2 years of age were sensitized to peanut. In the subgroup, individuals with detectable IgE antibodies reported a shorter reaction time after eating peanuts than individuals with normal IgE antibody levels (P<0.05). Conclusions: The reaction pattern to peanuts in Sweden is similar to that in many other countries despite a reported steady and low consumption. The severity of symptoms was connected to age and IgE antibody level. Patients with normal or low IgE antibody levels were not always free of symptoms even though their risk of allergic symptoms was reduced. [ABSTRACT FROM AUTHOR]

Background: Despite increasing awareness of peanut allergy, little is known of its prevalence. We report on a two‐stage interview survey conducted in Great Britain. Methods: A total of 16 434 adults (aged 15+ years) reported their own allergies and atopies and named cohabitants with peanut allergy (stage 1). Follow‐up interviews were conducted with identified sufferers from peanut allergy (stage 2). Results: At stage 1, peanut allergy was reported in 58 respondents and 205 other household members. When we accounted for cases where peanut allergy was unconfirmed or newly reported at stage 2, the prevalence, based on 124 confirmed sufferers, was estimated as 0.48% (95% confidence interval 0.40%–0.55%). The prevalence in children (0.61%, 0.41%–0.82%) was slightly higher than in adults; age‐of‐onset was strikingly earlier. Prevalence was strongly associated with other atopies, particularly tree‐nut allergy. Cases tended significantly to cluster in households. Half of cases had never consulted a doctor. Exactly 7.4% reported being hospitalized after a reaction. Conclusions: Peanut allergy is reported by 1 in 200 of the population and is commoner in those reporting other atopies. The fact of similar rates in children and adults argues against a recent marked rise in prevalence. The frequency and potential lethality of this disorder emphasize the need for sufferers to receive correct medical advice on management. [ABSTRACT FROM AUTHOR]

Background: Peanut allergy is common, potentially severe and rarely resolves causing impaired quality of life. No disease-modifying treatment exists and there is therefore a need to develop a therapeutic intervention. Aims of the study: The aim of this study was to investigate whether peanut oral immunotherapy (OIT) can induce clinical tolerance to peanut protein. Methods: Four peanut-allergic children underwent OIT. Preintervention oral challenges were performed to confirm clinical allergy and define the amount of protein required to cause a reaction (dose thresholds). OIT was then administered as daily doses of peanut flour increasing from 5 to 800 mg of protein with 2-weekly dose increases. After 6 further weeks of treatment, the oral challenge was repeated to define change in dose threshold and subjects continued daily treatment. Results: Preintervention challenges confirmed peanut allergy and revealed dose thresholds of 5–50 mg (1/40–1/4 of a whole peanut); one subject had anaphylaxis during challenge and required adrenaline injection. All subjects tolerated immunotherapy updosing to 800 mg protein and i.m. adrenaline was not required. Each subject tolerated at least 10 whole peanuts (approximately 2.38 g protein) in postintervention challenges, an increase in dose threshold of at least 48-, 49-, 55- and 478-fold for the four subjects. Conclusions: We demonstrated a substantial increase in dose threshold after OIT in all subjects, including the subject with proven anaphylaxis. OIT was well tolerated and conferred protection against at least 10 peanuts, more than is likely to be encountered during accidental ingestion. [ABSTRACT FROM AUTHOR]

Reports on a case of a patient with severe peanut allergy who experienced an allergic reaction after a kiss from his girlfriend, who had eaten peanuts two hours before. Background on the patient's anaphylactic reactions to various foods; Symptoms experienced by the patient; Level of the patient's allergen-specific immunoglobulin E to peanuts and soy based on the findings of the Pharmacia CAP system.

Examines the histamine content of peanuts. Impact of fermentation on the quantity of histamine; Determination of the protein concentration of raw peanuts; Comparison between the histamine concentration of raw and roasted peanuts.