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Until recently, glycan epitopes have not been documented by the WHO/IUIS Allergen Nomenclature Sub-Committee. This was in part due to scarce or incomplete information on these oligosaccharides, but also due to the widely held opinion that IgE to these epitopes had little or no relevance to allergic symptoms. Most IgE-binding glycans recognized up to 2008 were considered to be “classical” cross-reactive carbohydrate determinants (CCD) that occur in insects, some helminths and throughout the plant kingdom. Since 2008, the prevailing opinion on lack of clinical relevance of IgE-binding glycans has been subject to a reevaluation. This was because IgE specific for the mammalian disaccharide galactose-alpha-1,3-galactose (alpha-gal) was identified as a cause of delayed anaphylaxis to mammalian meat in the United States, an observation that has been confirmed by allergists in many parts of the world. Several experimental studies have shown that oligosaccharides with one or more terminal alpha-gal epitopes can be attached as a hapten to many different mammalian proteins or lipids. The classical CCDs also behave like haptens since they can be expressed on proteins from multiple species. This is the explanation for extensive in vitro cross-reactivity related to CCDs. Because of these developments, the Allergen Nomenclature Sub-Committee recently decided to include glycans as potentially allergenic epitopes in an adjunct section of its website (www.allergen.org). In this article, the features of the main glycan groups known to be involved in IgE recognition are revisited, and their characteristic structural, functional, and clinical features are discussed.

Background Small, basic peanut proteins are often poorly extracted in pH-neutral buffers that are optimal for the extraction of peanut storage proteins such as Ara h 1. As a result, such proteins are easily missed as potential allergens. Objective To analyse the allergenic composition of the basic peanut protein (BPP) fraction. Methods A peanut extract prepared at pH 4 was fractionated by physicochemical procedures. Chemical analysis was performed by SDS-PAGE and mass spectrometry. Because immunoblotting was found to be inefficient for most of these small basic proteins, IgE-binding activity was measured by coupling the fractions to CNBr-activated Sepharose, followed by incubation with sera from 55 Dutch peanut-allergic children and 125 I-labelled anti-IgE. Results Most IgE reactivity of the BPP fraction was due to the 5-7 kDa amino-terminal fragment of Ara h 1. This finding was confirmed by the use of the fragment in recombinant form, to which 25/55 of the sera was IgE-positive. Conclusion The amino-terminal fragment of Ara h 1, a member of a family of small anti-microbial proteins, is an allergen independent of the carboxy-terminal fragment of Ara h 1.

Oral immunotherapy (OIT) is a treatment option for patients with milk, egg, and peanut allergy, but data on the efficacy and safety of cashew OIT are limited.A cohort of 50 cashew-allergic patients aged ≥4 years, who were consecutively enrolled into cashew OIT (target dose 4000 mg protein) between 4/2016 and 12/2019. Fifteen cashew-allergic patients who continued cashew elimination served as observational controls. Co-allergy to pistachio and walnut was determined. Full desensitization rate and associated immunological changes in both groups were compared. Patients fully desensitized to cashew were instructed to consume a dose of 1200 mg cashew protein for 6 months and were then challenged to a full dose. Patients with co-allergy to pistachio or walnut were challenged to the respective nut.Forty-four of 50 OIT-treated patients (88%) compared to 0% in controls tolerated a dose of 4000 mg cashew protein at the end of the study (odds ratio 8.3, 95% CI 3.9-17.7, p 0.001). An additional three patients were desensitized to 1200 mg cashew protein, and three patients stopped treatment. Three patients (6%) were treated with injectable epinephrine for home reactions. Desensitized patients had decreased SPT, sIgE, basophil reactivity, and increased sIgG4, following treatment. Following cashew desensitization, all pistachio (n = 35) and four of eight walnut co-allergic patients were cross-desensitized to the respective nut. All (n = 44) patients consuming a low cashew dose for ≥6 months following desensitization passed a full-dose cashew OFC.Cashew OIT desensitizes most cashew-allergic patients and cross-desensitizes to pistachio. Safety is similar to OIT for other foods.

Evidence has suggested that major peanut allergen Ara h 1 activates dendritic cells (DCs) via interaction with DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin), a C-type lectin receptor, and contributes to development of peanut allergy. Since macrophages, as well as DCs, play a crucial role in innate immunity, we investigated whether natural Ara h 1 (nAra h 1) activates two different subsets of macrophages, human monocyte derived macrophage type 1 (hMDM1: pro-inflammatory model) and type 2 (hMDM2: anti-inflammatory model). hMDM1 and hMDM2 predominantly produced pro-inflammatory cytokines (IL-6 and TNF-α) and an anti-inflammatory cytokine (IL-10) in response to nAra h 1, respectively. hMDM2 took up nAra h 1 and expressed DC-SIGN at higher levels than hMDM1. However, small interfering RNA knockdown of DC-SIGN did not suppress nAra h 1 uptake and nAra h 1-mediated cytokine production in hMDM2. Inhibitors of scavenger receptor class A type I (SR-AI) suppressed the response of hMDM2, but not of hMDM1, suggesting that SR-AI is a major receptor in hMDM2 for nAra h 1 recognition and internalization. nAra h 1 appears to exert stimulatory capacity on DC and macrophages via different receptors. This study advances our understanding how a major peanut allergen interacts with innate immunity.

BACKGROUND The prevalence of sesame food allergy (SFA) is increasing worldwide with the potential of anaphylactic reactions upon exposure. Utility of specific component IgE testing as an alternative to the oral food challenge (OFC), the diagnostic standard, is being investigated. METHODS Patients (n = 42) with suspected SFA completed an open OFC to sesame. Diagnostic testing included serum levels of Ses i 1-specific IgE, skin prick test with high-protein extract, and basophil reactivity (% induced CD63 expression) for each patient. The diagnostic utility of these tests was evaluated at a 95% sensitivity, with the outcome measure being the number of OFCs required. RESULTS Twenty-seven patients (64%) were diagnosed with SFA. Ses i 1 IgE differed significantly between allergic and tolerant patients (p = .0001). ROC curve analysis for Ses i 1 IgE yielded an AUC of 0.88 ± 0.05. Levels of Ses i 1 IgE correlated to induced CD63+ expression on basophils (p = .0001). Ses i 1 IgE was not sufficiently robust as a single step for diagnosis. Used concurrently, BAT and Ses i 1 IgE yielded correct positive classifications for 25 of 27 sesame-allergic patients with two false positives (93% PPV). Both tests were negative in 5 non-allergic patients. Patients with divergent Ses i 1 IgE and BAT results required OFC (n = 10, 24% of patients). Alternatively, sequential use of BAT, ruling in SFA followed by Ses i 1 IgE diagnosing non-allergic patients, yielded a 89% PPV, with 19% requiring OFC. CONCLUSION Ses i 1 IgE and BAT used together can decrease the need for OFC in most SFA patients. A prospective cohort trial is necessary to validate these results.

Background: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen–hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen–allergic patients. Patients: A total of 835 cypress pollen–hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7. Results: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein–allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP. Conclusion: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.

Background Sensitization to peanuts and hazelnuts is common among young asthmatics and can be primary or a result of cross-reactivity. Sensitization as a result of cross-reactivity to birch pollen is typically associated to tolerance or mild and local symptoms upon intake of peanut or hazelnut. Aim The aim of this study was to investigate relationships between IgE antibody responses against peanut and hazelnut components, airway and systemic inflammation markers, lung function parameters and reported food hypersensitivity in a cohort of asthmatic children and young adults. Methods A population of 408 asthmatic individuals aged 10–35 years were investigated. Information on hypersensitivity symptoms upon intake of peanut or hazelnut were recorded in a standardized questionnaire. Fraction of exhaled nitric oxide (FeNO), blood eosinophil count (B-Eos), spirometry, methacholine challenge outcome and IgE antibodies to peanut and hazelnut allergens were measured by standard clinical and laboratory methods. Results Subjects sensitized to any of the peanut (Ara h 1, 2 or 3) or hazelnut (Cor a 9 or 14) storage proteins were significantly younger (17.6 vs 21.2 years), had higher levels of FeNO (23.2 vs 16.7 ppb) and B-Eos (340 vs 170 cells/mcl) than those displaying only pollen-related cross-reactive sensitization. Levels of FeNO correlated with levels of IgE to storage proteins in children, but not in adults. Levels of B-Eos correlated with levels of IgE to all allergen components investigated in children, but only to levels of IgE to storage proteins in adults. Anaphylaxis and skin reactions upon intake of peanuts or hazelnuts were more often reported among subjects sensitized to the respective storage proteins than among those with only pollen-related cross-reactive sensitization. As compared to peanut, hazelnut was more often reported to cause gastrointestinal symptoms and less often oral cavity symptoms. Conclusions Sensitization to peanut and hazelnut storage proteins was associated with higher levels of inflammation markers and food hypersensitivity symptoms in this population of subjects with asthma.

Background Common wheat (Triticum aestivum) and durum wheat (T. turgidum) are both involved in Baker's asthma (BA) and food allergy (FA) including wheat-dependent exercise-induced asthma (WDEIA). However, allergens in durum wheat have not been described, and the over-expression of T. turgidum non-specific lipid-transfer protein (nsLTPs) is considered to increase resistance to phytopathogens. Objective To identify and assess the allergenicity of nsLTP from T. turgidum. Methods Recombinant T. turgidum nsLTP Tri tu 14 was generated and tested for structural integrity (circular dichroism-spectroscopy) and purity (SDS-PAGE). Thirty-two wheat allergic patients were enrolled: 20 Spanish patients (BA) with positive bronchial challenge to wheat flour, and 12 Italian patients (wheat FA/WDEIA) with positive double-blind placebo-controlled food challenge/open food challenge (OFC) to pasta. IgE values to wheat, Tri tu 14, Tri a 14 (T. aestivum) and Pru p 3 (P. persica) were determined by ImmunoCAP testing. Allergenic potency (in vitro mediator release) and IgE cross-reactivity were investigated. Results Tri tu 14 was found to share 49% and 52% amino acid identity with Tri a 14 and Pru p 3, respectively. Among 25 Tri a 14 CAP positive sera, 23 (92%) were reactive to wheat extract, 22 (88%) to Tri tu 14 and 20 (80%) to Pru p 3. The correlation between Tri a 14 and Tri tu 14 specific IgE levels was r = 0.97 (BA) and r = 0.93 (FA/WDEIA), respectively. FA/WDEIA patients showed higher specific IgE values to Tri tu 14 and Pru p 3 than BA patients. Tri tu 14 displayed allergenic activity by mediator release from effector cells and IgE cross-reactivity with Pru p 3. The degree of IgE cross-reactivity between the two wheat nsLTPs varied between individual patients. Conclusions and clinical relevance Sensitization to Tri tu 14 likely appears to be more important in wheat FA/WDEIA than in BA. Over-expression of Tri tu 14 in wheat would represent a risk for patients with nsLTP-mediated FA.

BACKGROUND: Walnut allergy is common across the globe, but data on the involvement of individual walnut components are scarce.OBJECTIVES: To identify geographical differences in walnut component sensitization across Europe, explore cosensitization and cross-reactivity, and assess associations of clinical and serological determinants with severity of walnut allergy.METHODS: As part of the EuroPrevall outpatient surveys in 12 European cities, standardized clinical evaluation was conducted in 531 individuals reporting symptoms to walnut, with sensitization to all known walnut components assessed in 202 subjects. Multivariable Lasso regression was applied to investigate predictors for walnut allergy severity.RESULTS: Birch-pollen-related walnut sensitization (Jug r 5) dominated in Northern and Central Europe and lipid transfer protein sensitization (Jug r 3) in Southern Europe. Profilin sensitization (Jug r 7) was prominent throughout Europe. Sensitization to storage proteins (Jug r 1, 2, 4, and 6) was detected in up to 10% of subjects. The walnut components that showed strong correlations with pollen and other foods differed between centers. The combination of determinants best predicting walnut allergy severity were symptoms upon skin contact with walnut, atopic dermatitis (ever), family history of atopic disease, mugwort pollen allergy, sensitization to cat or dog, positive skin prick test result to walnut, and IgE to Jug r 1, 5, 7, or carbohydrate determinants (area under the curve = 0.81; 95% CI, 0.73-0.89).CONCLUSIONS: Walnut-allergic subjects across Europe show clear geographical differences in walnut component sensitization and cosensitization patterns. A predictive model combining results from component-based serology testing with results from extract-based testing and information on clinical background allows for good discrimination between mild to moderate and severe walnut allergy.

Background Severe allergy to fruits mediated by a 7 kDa allergen belonging to the gibberellin-regulated protein (GRP) family is known to be associated with Cupressaceae pollinosis. Objective To identify and characterize Cupressaceae pollen allergens involved in GRP-related fruit allergy. Methods Pru p 7-related proteins from pollen of Cupressus sempervirens, Juniperus ashei and Cryptomeria japonica were identified using a rabbit anti-Pru p 7 antiserum, purified chromatographically and sequenced by mass spectrometry and bioinformatic comparisons. The C sempervirens protein was produced as a recombinant allergen in Pichia pastoris. IgE antibody binding to pollen GRP proteins was analysed in a peach allergic (n = 54) and a cypress pollen allergic (n = 88) patient population from southern France using ImmunoCAP. Results In each of the three Cupressaceae species studied, a 7 kDa pollen protein related to Pru p 7 was identified and found to comprise an amino acid sequence of 63 residues in length, 92%-98% identical to each other and 67%-68% identical to Pru p 7. The C sempervirens, J ashei and C japonica GRP allergens have been officially recognized by the WHO/IUIS Allergen Nomenclature Sub-Committee and named Cup s 7, Jun a 7 and Cry j 7, respectively. Recombinant Cup s 7 showed IgE antibody binding capacity comparable to that of the purified natural allergen. Among 51 peach allergic subjects sensitized to Pru p 7, substantially higher levels of IgE to Cup s 7 than to Pru p 7 were found. Further, the pollen protein was able to completely outcompete IgE binding to Pru p 7, while the reverse competition effect was modest, consistent with primary sensitization by the pollen allergen. Conclusion and clinical relevance Pru p 7-related pollen allergens from three Cupressaceae species have been characterized and may become useful for the identification of pollinosis patients at risk of developing severe fruit allergy.

Background Diagnostic methods for distinguishing walnut-allergic patients from walnut-sensitized but walnut-tolerant individuals are limited. Furthermore, characteristics of single walnut versus dual walnut-pecan allergy are lacking. Objective To provide clinical and molecular characteristics of walnut- and pecan-allergic patients. Methods A prospective cohort study of 76 walnut-sensitized patients was performed. Walnut skin prick test and serum measurements of specific IgE to walnut and its components were performed. Patients were challenged to walnut and pecan unless they regularly consumed walnut and pecan. Results Of the 76 patients studied, 61 were diagnosed as walnut-allergic and 15 as walnut-tolerant. IgE levels greater than or equal to 0.35 kUA/L to Jug r 1 or 4 provided the best diagnostic method for identifying walnut-allergic patients (accuracy, 0.93). Of the 61 walnut-allergic patients, 49 were pecan-allergic whereas 12 were pecan-tolerant. None of the walnut-tolerant patients was allergic to pecan. Dual allergic patients had significantly lower walnut reaction dose (median, 100 mg vs 1230 mg; P Conclusions Walnut components are helpful in diagnosing walnut allergy and in identifying patients with pecan coallergy. Competitive ELISA indicates that pecan comprises a subset of the allergenic determinants of walnut.

BACKGROUND: Peach is a common elicitor of food allergic reactions. Peach-induced immediate reactions may occur as benign pollen-food syndromes, usually due to birch pollen-related PR-10 cross-reactivity in temperate climates, and as potentially severe primary food allergies, predominantly related to nsLTP Pru p 3 in Mediterranean regions. The newly described peach allergen Pru p 7 has gained recent attention as a potential peach allergy severity marker. Sensitization to Pru p 7 and its allergenic homologues of the gibberellin-regulated protein family occurs in areas with high Cupressaceae tree pollen exposure. OBJECTIVE: We sought to investigate the distribution, clinical characteristics and molecular associations of Pru p 7 sensitization among subjects with suspected peach allergy in different regions of France. METHODS: Subjects with suspected peach allergy (n = 316) were included. Diagnostic work-up was performed according to current guidelines, including open food challenge when required. IgE antibody measurements and competition experiments were performed using the ImmunoCAP assay platform. RESULTS: Sensitization to Pru p 7 was present in 171 (54%) of all subjects in the study and in 123 of 198 (62%) diagnosed as peach allergic, more than half of whom were sensitized to no other peach allergen. Frequency and magnitude of Pru p 7 sensitization were associated with the presence of peach allergy, the clinical severity of peach-induced allergic reactions and the level of cypress pollen exposure. Cypress pollen extract completely outcompeted IgE binding to Pru p 7. Pru p 7 was extremely potent in basophil activation tests. CONCLUSION AND CLINICAL RELEVANCE: A subtype of Cupressaceae pollinosis, characterized by Pru p 7 sensitization, can be an underlying cause of severe peach allergy.

Background The presence of sesame in Western diet is increasing, making its avoidance by sesame-allergic patients more challenging. Objective To report the efficacy and safety of sesame oral immunotherapy (OIT). Methods Sixty patients aged 4 years or older, diagnosed as sesame-allergic on the basis of a positive oral food challenge, were consecutively enrolled into OIT between November 2014 and November 2017. Fifteen patients with sesame allergy, based on a positive oral food challenge or a recent immediate reaction, and a positive skin prick test result or specific IgE, continued sesame elimination and served as observational controls. Immunologic parameters were measured in a subset (OIT, n = 16; controls, n = 11) at the start and end of the study. Fully desensitized patients continued daily consumption of 1200 mg sesame protein and challenged with 4000 mg after more than 6 months. Results Fifty-three OIT-treated patients (88.4%) were fully desensitized to sesame, compared with 0% of controls. Four additional patients (total 57 of 60 = 95%) were desensitized to more than 1000 mg protein. Reactions occurred in 4.7% of hospital doses and 1.9% of home doses. Epinephrine-treated reactions occurred in 16.7% of patients for hospital and 8.3% for home doses. Significant decreases in rSes i 1 IgE (P = .007) and basophil reactivity (P = .001) and increases in sesame and rSes i 1 IgG4 (P = .001) occurred in OIT-treated patients but not in controls. Forty-seven patients desensitized to 4000 mg were evaluated more than 6 months after reaching maintenance. Only mild reactions were reported during maintenance, and all passed the 4000-mg challenge. Conclusions Sesame-OIT is an effective alternative to sesame avoidance in allergic patients. The potential for adverse events necessitates its performance in specialized centers.

Introduction Les proteines regulees par la gibberelline (GRP), inconnues jusqu’en 2013, comptent aujourd’hui une dizaine de membres responsables de reactions croisees pollens-aliments. Alors que la peche, l’abricot japonais et l’orange ont ete les premieres sources de GRP identifiees, l’anamnese des patients decrivant des reactions cliniques a un large eventail d’autres fruits suggere l’implication des GRP. Nous avons cherche a identifier les fruits, autres que la peche, associes a une sensibilisation aux GRP dans le sud de la France. Methodes Trois cent quatre vingt six patients (âge median 19 ans, 1–74 ans ; sex-ratio 0,9) consultant pour suspicion d’allergie aux fruits ont ete inclus. Le diagnostic d’allergie a ete pose par l’association histoire clinique convaincante et demonstration d’une sensibilisation au fruit suspecte. Les IgE contre Pru p 1, Prup 3, Pru p 4 et Pru p 7 ont servi d’allergenes marqueurs pour la sensibilisation vis-a-vis des familles PR-10, LTP, profiline et GRP et Cup a 1 pour la sensibilisation aux cupressacees. Resultats Une allergie aux fruits autres que la peche a ete demontree chez 204 (53 %) patients, dont 116 (63 %) etaient sensibilises a Pru p 7. Les autres fruits des rosacees, le kiwi, les agrumes, la tomate et la figue representaient 91 (24 %), 46 (12 %), 34 (9 %), 19 (5 %) et 7 (2 %) patients, respectivement. La prevalence de la sensibilisation Pru p 7 variait de 86 % (figue) a 42 % (tomate). La prevalence de la monosensibilisation a Pru p 7 (sans IgE Pru p 1,3 et 4) etait la plus elevee dans l’allergie aux agrumes et a la figue (85 et 83 %) et la plus faible dans l’allergie au kiwi (27 %). Tous les grades de severite etaient representes. Un cofacteur, generalement l’effort, etait rapporte chez 14 % des patients Pru p 7. Un « syndrome multi fruits » (allergie a plus de 3 familles de fruits), etait present chez 92 patients (24 %), dont 52 (57 %) sensibilises a Pru p 7 (28, soit 54 %, de monosensibilisation). Tous les patients sensibilises a Pru p 7 l’etaient aussi aux cupressacees. Conclusion La sensibilisation a Pru p 7, souvent isolee, est frequente chez les patients mediterraneens allergiques aux fruits et sensibilises aux Cupressacees.

SummaryBackground Non-specific lipid transfer proteins (nsLTP) are considered to provoke allergic symptoms to plane tree pollen, which are frequently associated with peach allergy. Objective The objective was to clone the cDNA of plane pollen nsLTP Pla a 3, to characterize IgE-binding and allergenic potency of recombinant Pla a 3 in comparison to its natural counterpart and peach nsLTP Pru p 3. Methods Natural Pla a 3 was purified from plane pollen and analysed by mass spectrometry (MS). Recombinant Pla a 3 was characterized by SDS-PAGE and CD spectroscopy. Specific IgE to extract, components of plane pollen and Pru p 3 was measured by ImmunoCAP in sera of patients allergic to either plane pollen (n = 10), peach (n = 15) or both (n = 15). Biological potency of the proteins was investigated by in vitro mediator release assays and IgE cross-reactivity by competitive ELISA. Results Two Pla a 3 isoforms were identified. Recombinant Pla a 3 showed high purity, structural integrity, IgE-binding capacity comparable to nPla a 3 and biological potency. Sensitization to plane pollen extract was confirmed in 24/25 plane pollen allergics. The frequency of sensitization to Pla a 3 was 53% among patients allergic to both plane pollen and peach and 10% among plane pollen allergics tolerating peach where most patients were sensitized to Pla a 1. Pla a 3 and Pru p 3 showed strong bi-directional IgE cross-reactivity in patients allergic to peach and plane pollen, but not in peach allergics tolerating plane pollen. Levels of IgE-binding were generally higher to Pru p 3 than to Pla a 3. Conclusion Sensitization to Pla a 3 is relevant in a subgroup of plane pollen allergics with concomitant peach allergy. IgE testing with Pla a 3 may serve as a marker to identify plane pollen allergic patients at risk of LTP-mediated food reactions and thereby improve in vitro diagnostic procedures.

Walnut is an important elicitor of food allergy in children and adults with a high rate of severe reactions. Multicenter studies using a common clinical protocol and a comprehensive allergen are lacking.To investigate potential correlations between molecular sensitization patterns and clinical characteristics of walnut-allergic patients.A total of 91 walnut-allergic subjects and 24 tolerant controls from Switzerland, Germany, and Spain were included. Walnut allergy was established by food challenge in all but anaphylactic subjects. Specific IgE (sIgE) to walnut extract, rJug r 1 (2S albumin), rJug r 3 (nonspecific lipid transfer protein 1), nJug r 4 (11S globulin), rJug r 5 (PR-10 protein), 2 vicilin fractions, profiling, and cross-reactive carbohydrate determinant was determined by ImmunoCAP. A threshold of 0.10 kUSensitivity of sIgE to walnut extract was 87% and increased to 96% for the sum of all walnut components. sIgE to walnut extract and all walnut components, except rJug r 5, was significantly higher in patients younger than 14 years at inclusion. Stratification by age at onset of walnut allergy led to similar results. All patients younger than 14 years had severe reactions, whereas 38% of patients 14 years or older were mild reactors. Severe reactors (n = 70) had higher sIgE levels than did mild reactors (n = 21) to walnut extract (P.0001), rJug r 1 (P .0001), nJug r 4 (P = .0003), and both vicilin fractions (P .0001), but not to Jug r 3 and Jug r 5.Sensitization to walnut storage proteins is acquired in childhood and correlates with severe reactions. sIgE levels to storage proteins Jug r 1 and Jug r 4 and vicilin fractions, but not to nonspecific lipid transfer protein and PR-10 proteins, correlate with systemic reactions to walnut.

Summary Background The safety and efficacy of oral immunotherapy for tree nut allergy has not been demonstrated to date, and its effectiveness is complicated by the high prevalence of co-allergies to several nuts. This study aimed to investigate the use of walnut oral immunotherapy in the desensitisation of walnut and additional tree nuts in patients who are co-allergic to several nuts. Methods In a single-centre, prospective cohort study (the Nut Co-Reactivity ACquiring Knowledge for Elimination Recommendations study) at the Institute of Allergy, Immunology, and Paediatric Pulmonology at the Yitzhak Shamir Medical Centre, we recruited patients aged 4 years or older who were allergic to walnut, with or without co-allergy to pecan, hazelnut, and cashew. The diagnosis of each food allergy was based on a positive skin prick test or specific serum IgE (≥0·35 kUA/L) to the corresponding nut together with a positive oral food challenge, unless an immediate (within 2 h of exposure) reaction in the past year had been documented. Patients with uncontrolled asthma or a medical contraindication to receive adrenaline were excluded. Patients were assigned to walnut oral immunotherapy or the control group (observation and strict dietary exclusion) on the basis of the order of presentation to the clinic. Oral immunotherapy began with a 4-day dose-escalation phase to establish the single highest tolerated dose, which was consumed daily at home for 24 days; subsequent monthly dose escalations were repeated until 4000 mg walnut protein was achieved. Patients who were desensitised to walnut continued to consume 1200 mg walnut protein daily for 6 months as maintenance. The primary outcome was walnut desensitisation (passing an oral food challenge with 4000 mg of walnut protein) at the end of the study, analysed by intention to treat. In patients who were co-allergic to pecan, hazelnut, and cashew, the proportion who achieved cross-desensitisation to these nuts in addition to walnut desensitisation was examined. Findings 73 patients with a walnut allergy were enrolled between May 15, 2016, and Jan 14, 2018. 49 (89%) of 55 patients in the oral immunotherapy group were desensitised to walnut compared with none of 18 patients in the control group (odds ratio 9·2, 95% CI 4·3–19·5; p Interpretation Walnut oral immunotherapy can induce desensitisation to walnut as well as cross-desensitisation to pecan and hazelnut in patients who have tree nut co-allergies, with a reasonable safety profile. A low daily dose of the allergen maintains desensitisation. Funding None.

Highlights • Beginning and evolution of the official Allergen Nomenclature system 1980–2018. • Allergen Names abbreviated genus, species and number. • Expected data including characterization of protein amino acid sequence, cDNA, human serum donors and experimental data. • Challenges of identifying allergens including exposure and complex human exposure and immunity. • Complexity of new methods including “omics”. Abstract A systematic nomenclature for allergens originated in the early 1980s, when few protein allergens had been described. A group of scientists led by Dr. David G. Marsh developed a nomenclature based on the Linnaean taxonomy, and further established the World Health Organization/International Union of Immunological Societies (WHO/IUIS) Allergen Nomenclature Sub-Committee in 1986. Its stated aim was to standardize the names given to the antigens (allergens) that caused IgE-mediated allergies in humans. The Sub-Committee first published a revised list of allergen names in 1986, which continued to grow with rare publications until 1994. Between 1994 and 2007 the database was a text table online, then converted to a more readily updated website. The allergen list became the Allergen Nomenclature database (www.allergen.org), which currently includes approximately 880 proteins from a wide variety of sources. The Sub-Committee includes experts on clinical and molecular allergology. They review submissions of allergen candidates, using evidence-based criteria developed by the Sub-Committee. The review process assesses the biochemical analysis and the proof of allergenicity submitted, and aims to assign allergen names prior to publication. The Sub-Committee maintains and revises the database, and addresses continuous challenges as new “omics” technologies provide increasing data about potential new allergens. Most journals publishing information on new allergens require an official allergen name, which involves submission of confidential data to the WHO/IUIS Allergen Nomenclature Sub-Committee, sufficient to demonstrate binding of IgE from allergic subjects to the purified protein.

International audience; Molecular-based allergy diagnostic kits using standard IgE reagents such as peach extract, Pm p 1 (PR-10), Pru p 3 (non-specific lipid transfer protein), Pru p 4 (profilin), and cross-reactive carbohydrate determinants, are unable to identify the offending allergen in certain patients with peach allergy in Southern France, despite positive skin tests and a convincing clinical history. The constant and high positivity of the basophil activation test with peach extract in such patients suggests the involvement of a molecular peach allergen not included in existing in vitro diagnostic kits. Herein we report that peamaclein (Pm p 7) is a major allergen in peach-allergic patients in the Mediterranean (Marseille) region and we describe the epidemiological, clinical and laboratory characteristics associated with this novel allergen. (C) 2017 Published by Elsevier Masson SAS.; Certaines allergies immédiates à la pêche ne sont pas élucidées sur le plan moléculaire par l’exploration des IgE spécifiques utilisées en routine : extrait de pêche, Pru p 1 (PR-10), Pru p 3 (protéine de transfert lipidique), Pru p 4 (profiline) et groupements glucidiques à réactivité croisée, et ce malgré des tests cutanés fortement positifs et une histoire clinique convaincante. L’exploration de ces patients par un test d’activation des basophiles en présence d’extrait de pêche est fortement positive, suggérant l’implication d’un allergène moléculaire de la pêche, absent des outils diagnostiques in vitro actuels. Nous rapportons ici la forte prévalence de la sensibilisation vis-à-vis de la peamacléine (Pru p 7) chez les patients méditerranéens allergiques à la pêche (région de Marseille), ainsi que les caractères épidémiologiques, cliniques et biologiques associés à ce nouvel allergène.

BACKGROUND: Component-resolved diagnosis (CRD) has revealed significant associations between IgE against individual allergens and severity of hazelnut allergy. Less attention has been given to combining them with clinical factors in predicting severity. AIM: To analyze associations between severity and sensitization patterns, patient characteristics and clinical history, and to develop models to improve predictive accuracy. METHODS: Patients reporting hazelnut allergy (n = 423) from 12 European cities were tested for IgE against individual hazelnut allergens. Symptoms (reported and during Double-blind placebo-controlled food challenge [DBPCFC]) were categorized in mild, moderate, and severe. Multiple regression models to predict severity were generated from clinical factors and sensitization patterns (CRD- and extract-based). Odds ratios (ORs) and areas under receiver-operating characteristic (ROC) curves (AUCs) were used to evaluate their predictive value. RESULTS: Cor a 9 and 14 were positively (OR 10.5 and 10.1, respectively), and Cor a 1 negatively (OR 0.14) associated with severe symptoms during DBPCFC, with AUCs of 0.70-073. Combining Cor a 1 and 9 improved this to 0.76. A model using a combination of atopic dermatitis (risk), pollen allergy (protection), IgE against Cor a 14 (risk) and walnut (risk) increased the AUC to 0.91. At 92% sensitivity, the specificity was 76.3%, and the positive and negative predictive values 62.2% and 95.7%, respectively. For reported symptoms, associations and generated models proved to be almost identical but weaker. CONCLUSION: A model combining CRD with clinical background and extract-based serology is superior to CRD alone in assessing the risk of severe reactions to hazelnut, particular in ruling out severe reactions.

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: 68 peanut allergic subjects and 82 tolerant controls from 11 European countries were included. Allergy to peanut and lowest symptom-eliciting-dose were 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 were determined using ImmunoCAP. RESULTS: 78% of peanut allergics were sensitised to peanut extract and 90% to at least one peanut component. rAra h 2 was the sole major allergen for the peanut allergic population. Geographic differences were observed for rAra h 8 and rAra h 9, which were major allergens for central/western and southern Europeans, respectively. Sensitisation to rAra h 1 and 2 were exclusively observed in early onset peanut allergy. Peanut tolerant subjects were frequently sensitised to rAra h 8 or 9 but not to storage proteins. Sensitisation 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. This article is protected by copyright. All rights reserved.

Allergen-specific IgGWe sought to investigate serum food sIgGSera from 71 pediatric patients with EoE and 210 early adolescent children from an unselected birth cohort (Project Viva) were assayed for sIgGIn the EoE cohort high-titer sIgGsIgG

Aim Over the past few decades, the incidence of food allergies has risen and Sweden has increased its import of peanuts and exotic nuts, such as cashew nuts, which may cause severe allergic reactions. This study aimed to retrospectively investigate paediatric emergency visits due to food reactions over a 10-year period, focusing on reactions to peanuts and tree nuts. Methods Emergency visits to Uppsala University Children's Hospital, Sweden, between September 2001 and December 2010, were reviewed, and cases containing diagnostic codes for anaphylaxis, allergic reactions or allergy and hypersensitivity not caused by drugs or biological substances were retrieved. Results We analysed 703 emergency visits made by 578 individuals with food allergies. Peanuts and tree nuts accounted for 50% of the food allergies and were more frequently associated with adrenaline treatment and hospitalisation than other foods. Cashew nut reactions increased over the study period, and together with peanuts, they were responsible for more anaphylactic reactions than hazelnuts. Conclusion Peanut and tree nut reactions were more likely to result in adrenaline treatment and hospitalisation than other food reactions. Peanut and cashew nut reactions were more likely to cause anaphylaxis than hazelnuts. Cashew nut reactions increased during the study period.

Scope The aim was to investigate the potential contribution of a major birch pollen Bet v 1-homologous allergen to birch pollen-associated tomato fruit allergy. Methods and results Two isoforms of a Bet v 1-homologous protein (designated Sola l 4) from tomato fruit were identified by cDNA-cloning and produced as recombinant proteins. Allergen-specific IgE levels to tomato, birch pollen, Bet v 1, and Sola l 4 were determined in birch pollen allergic patients with allergy or tolerance to tomato. Sola l 4 was recognized in 76% of birch/tomato allergic patients, while tomato- and Bet v 1-specific IgE was detectable in 64% and 81% of sera. Almost all patients sensitized to Bet v 1 reacted with Sola l 4. Both Sola l 4 isoforms displayed allergenic potency and IgE-cross-reactivity with Bet v 1 as investigated by competitive ELISA and in vitro mediator release assay. Nevertheless, the reactivity pattern of patients' sera was diverse. Conclusion Sola l 4, a novel pathogenesis related-10 protein, qualifies as major allergen in tomato fruits. Data suggest Sola l 4 as class II allergen. IgE-testing using Sola l 4 showed low clinical specificity, but high sensitivity in tomato allergic patients and will further improve component-resolved allergy diagnosis.

Introduction La sensibilisation vis-a-vis de Pru p 7 est frequemment associee a une allergie severe a la peche. Chez ces patients, le test de reintroduction orale n’est pas denue de risques. Nous avons cherche a determiner si le test d’activation des basophiles (TAB) etait predictif de la severite clinique de l’allergie Pru p 7-dependante a la peche. Methodes Neuf patients allergiques a la peche et sensibilises a Pru p 7 et un patient tolerant a la peche et non sensibilise a Pru p 7 ont ete etudies. Le TAB (identification CD193 + faible granulosite, activation CD63) a ete realise avec Pru p 7 sous forme naturelle purifiee (n) et recombinante (r) a 12 concentrations. L’analyse a ete realisee selon les criteres habituels : CE50, CDsens, plus faible concentration activatrice et activation maximale obtenue. D’autres familles allergeniques (LTP n et r Pru p 3, PR-10 rMal d 1, profiline rTri a 12) et l’extrait de peche ont ete testes en parallele. Les resultats des dosages unitaires d’IgE rPru p 1, rPru p 3, rPru p 4, rPru p 7 et groupements glucidiques vegetaux a reactivite croisee, ainsi qu’une exploration par micropuce ISAC etaient disponibles. Resultats Pour les neuf patients allergiques a la peche, Pru p 7 a induit une forte activation des basophiles, aucune activation n’etant observee chez le patient tolerant. Les autres allergenes moleculaires n’ont pas induit d’activation. Les courbes dose-reponse montrent un fort potentiel d’activation par Pru p 7, avec des medianes de 0,05 ng/mL pour EC50, 2000 pour CDsens et 0,006 ng/mL pour la plus faible concentration activatrice. EC50 et la plus faible concentration activatrice etaient plus bas chez les patients reagissant cliniquement a la peche sans cofacteur (n = 6) que chez ceux necessitant l’intervention d’un cofacteur (n = 3), avec une tendance similaire pour CDsens. Le rapport entre l’activation maximale induite par rPru p 7 et l’activation induite par anti-RFcɛI etait proche de 1. Conclusion Dans cette etude pilote, le TAB avec Pru p 7 semble capable de predire la gravite de la reaction clinique a la peche, suggerant sa possible utilisation en remplacement du test de reintroduction chez certains patients.