A European-Japanese study on peach allergy : IgE to Pru p 7 associates with severity

Funding Information: M. Fernández‐Rivas received grants or contracts from Instituto de Salud Carlos III, Spanish Government, Aimmune Therapeutics, Diater, and Novartis; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Aimmune Therapeutics, Ediciones Mayo S.A., Diater, Ga2LEN, HAL Allergy, GSK, MEDSCAPE, NOVARTIS, and EPG Health; is member of the Data Safety Monitoring Board at DBV and advisory board at Aimmune Therapeutics, Novartis, Reacta Healthcare, and SPRIM. B. Ballmer‐Weber received consulting fees from ALK, Allergopharma, Menarini, Sanofi, Novartis, Thermofisher and Aimune and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from ALK, Menarini, Sanofi, Novartis, and Thermofisher. F. De Blay received grants or contract from Aimmune, Stallergenes Greer, GSK, ALK, Chiesi, and Regeneron. Y. Fukutomi received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Thermo Fisher Diagnostics KK. K. Hoffmann‐Sommergruber received funding from Danube Allergy Research Cluster funded by the Country of Lower Austria to (P07) KHS; was Member of the EAACI board until 2022/07. J. Lidholm is employee at Thermo Fisher Scientific. E.N.C Mills received grants or has contracts from Food Standards Agency Patterns and prevalence of adult food allergy (FS101174), European Food Safety Authority (ThRAll; allergenicity prediction [with EuroFIR]) and from Innovate (ML for food allergy); has applied for a patent on oral food challenge meal formulations for diagnosis of food allergy; is member of the Advisory Board of Novartis and Advisory Committee on Novel Foods and Processes; and is shareholder of Reacta Healthcare Ltd. N.G. Papadopoulos received grants or contracts from Capricare, Nestle, Numil, Vianex; received consultancy fees from Abbott, Abbvie, Astra Zeneca, GSK, HAL, Medscape, Menarini/Faes Farma, Mylan, Novartis, Nutricia, OM Pharma, and Regeneron/Sanofi. S. Vieths received royalties or licenses from Schattauer Allergologie Handbuch, Elsevier Nahrungsmittelallergien and Intoleranzen and Karger Food Allergy: Molecular Basis and Clinical Practice; support for attending meetings and/or travel as Associate Editor of the Journal of Allergy and Clinical Immunology. R. van Ree received consulting fees from HAL Allergy, Citeq, Angany, Reacta Healthcare, Mission MightyMe, and Ab Enzymes; received payment of honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from HAL Allergy, Thermo Fisher Scientific and ALK; received payment for expert testimony from AB Enzymes; has stock option at Angany. The rest of the authors declare that they have no relevant conflicts of interest. Funding Information: This work was funded by the European Commission under the 6th Framework Programme through EuroPrevall (FP6‐FOOD‐CT‐2005‐514000), and the 7th Framework Programme iFAAM (grant agreement no. 31214). Funding Information: We thank all the patients for their participation in the study. We would like to thank ALK Abello (Madrid, Spain) for their generous gift of SPT reagents. We thank Angelica Ehrenberg, Jonas Östling and Lars Mattsson (Uppsala) for preparing recombinant Cup s 7 and custom ImmunoCAP tests for this study. We acknowledge the support by the 6th and 7th Framework Programmes of the EU, for EuroPrevall (FP6‐FOOD‐CT‐2005‐514000) and iFAAM (Grant agreement no. 312147), respectively. We thank Alejandro Gonzalo Fernández (Hospital Clinico San Carlos, IdISSC, Madrid) for implementing the FASS in the data set. Publisher Copyright: © 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.BACKGROUND: Pru p 3 and Pru p 7 have been implicated as risk factors for severe peach allergy. This study aimed to establish sensitization patterns to five peach components across Europe and in Japan, to explore their relation to pollen and foods and to predict symptom severity. METHODS: In twelve European (EuroPrevall project) and one Japanese outpatient clinic, a standardized clinical evaluation was conducted in 1231 patients who reported symptoms to peach and/or were sensitized to peach. Specific IgE against Pru p 1, 2, 3, 4 and 7 and against Cup s 7 was measured in 474 of them. Univariable and multivariable Lasso regression was applied to identify combinations of parameters predicting severity. RESULTS: Sensitization to Pru p 3 dominated in Southern Europe but was also quite common in Northern and Central Europe. Sensitization to Pru p 7 was low and variable in the European centers but very dominant in Japan. Severity could be predicted by a model combining age of onset of peach allergy, probable mugwort, Parietaria pollen and latex allergy, and sensitization to Japanese cedar pollen, Pru p 4 and Pru p 7 which resulted in an AUC of 0.73 (95% CI 0.73-0.74). Pru p 3 tended to be a risk factor in South Europe only. CONCLUSIONS: Pru p 7 was confirmed as a significant risk factor for severe peach allergy in Europe and Japan. Combining outcomes from clinical and demographic background with serology resulted in a model that could better predict severity than CRD alone.Peer reviewe

How much is too much? Threshold dose distributions for 5 food allergens

Background Precautionary labeling is used to warn consumers of the presence of unintended allergens, but the lack of agreed allergen thresholds can result in confusion and risk taking by patients with food allergy. The lack of data on threshold doses below which subjects are unlikely to react is preventing the development of evidence-based allergen management strategies that are understood by clinician and patient alike. Objective We sought to define threshold dose distributions for 5 major allergenic foods in the European population. Methods Patients with food allergy were drawn from the EuroPrevall birth cohort, community surveys, and outpatient clinic studies and invited to undergo a food challenge. Low-dose, double-blind, placebo-controlled food challenges were undertaken with commercially available food ingredients (peanut, hazelnut, celery, fish, and shrimp) blinded into common matrices. Dose distributions were modeled by using interval-censoring survival analysis with 3 parametric approaches. Results Of the 5 foods used for challenge, 4 produced similar dose distributions, with estimated doses eliciting reactions in 10% of the allergic population (ED10), ranging from 1.6 to 10.1 mg of protein for hazelnut, peanut, and celery with overlapping 95% CIs. ED10 values for fish were somewhat higher (27.3 mg of protein), although the CIs were wide and overlapping between fish and plant foods. Shrimp provided radically different dose distributions, with an ED10 value of 2.5 g of protein. Conclusion This evidence base will contribute to the development of reference doses and action levels for allergens in foods below which only the most sensitive subjects might react. © 2014 American Academy of Allergy, Asthma & Immunology

IMerge: Results from a phase 3, randomized, double-blind, placebo-controlled study of imetelstat in patients (pts) with heavily transfusion dependent (TD) non-del(5q) lower-risk myelodysplastic syndromes (LR-MDS) relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESA)

7004 Background: Unmet needs remain for red blood cell (RBC) TD pts with LR-MDS R/R or ineligible for ESA. In P2 of the IMerge study (NCT02598661), heavily RBC TD ESA R/R non-del(5q) LR-MDS pts naive to lenalidomide and hypomethylating agents (len/HMA) treated with imetelstat, a telomerase inhibitor, achieved durable and continuous transfusion independence (TI). We report primary data from the P3 study of imetelstat in such pts. Methods: Heavily RBC TD ESA R/R non-del(5q) LR-MDS pts naive to len/HMAs were randomized 2:1 to receive imetelstat 7.5 mg/kg or placebo every 4 wks. Primary endpoint was 8-wk TI; subgroup analyses included IPSS risk, prior transfusion burden and ring sideroblast (RS) status. Secondary endpoints included 24-wk TI, TI duration and hematologic improvement-erythroid (HI-E). Variant allele frequency (VAF) changes were explored. Results: As of Oct 2022, 178 pts were randomized. The primary endpoint was met (Table); 39.8% vs 15.0% of pts receiving imetelstat vs placebo, respectively, achieved 8-wk TI. The rate of 8-wk TI was significantly higher with imetelstat vs placebo across subgroups, including RS negative pts. Median TI duration was significantly longer for imetelstat vs placebo, 51.6 vs 13.3 wks, P 80% were reversible to Grade ≤2 within 4 wks. Conclusions: For this LR-MDS pt population, imetelstat demonstrated statistically significant and clinically meaningful efficacy with high 8- and 24-wk TI rates, prolonged TI duration and increased hemoglobin. VAF reduction and its correlation to clinical endpoints support imetelstat’s disease-modifying potential. Safety results were consistent with prior reported experience. Clinical trial information: NCT02598661 . [Table: see text

IgE recognition patterns in peanut allergy are age dependent: Perspectives of the EuroPrevall study

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. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Health sector costs of self-reported food allergy in Europe: A patient-based cost of illness study

Introduction: Food allergy is a recognized health problem, but little has been reported on its cost for health services. The EuroPrevall project was a European study investigating the patterns, prevalence and socio-economic cost of food allergy. Aims: To investigate the health service cost for food-allergic Europeans and the relationship between severity and cost of illness. Methods: Participants recruited through EuroPrevall studies in a case-control study in four countries, and cases only in five countries, completed a validated economics questionnaire. Individuals with possible food allergy were identified by clinical history, and those with food-specific immunoglobulin E were defined as having probable allergy. Data on resource use were used to estimate total health care costs of illness. Mean costs were compared in the case-control cohorts. Regression analysis was conducted on cases from all 9 countries to assess impact of country, severity and age group. Results: Food-allergic individuals had higher health care costs than controls. The mean annual cost of health care was international dollars (I$)2016 for food-allergic adults and I$1089 for controls, a difference of I$927 (95$324-I$1530). A similar result was found for adults in each country, and for children, and was not sensitive to baseline demographic differences. Cost was significantly related to severity of illness in cases in nine countries. Conclusions: Food allergy is associated with higher health care costs. Severity of allergic symptoms is a key explanatory factor. © 2013 The Author 2013. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved

IgE recognition patterns in peanut allergy are age dependent: perspectives of the EuroPrevall study.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageWe 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.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.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).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.EU, EuroPrevall FP6-FOOD-CT-2005-51400