Lupine Allergy: Not Simply Cross-Reactivity with Peanut or Soy

Background: Reports of lupine allergy are increasing as its use in food products increases. Lupine allergy might be the consequence of cross-reactivity after sensitization to peanut or other legumes or de novo sensitization. Lupine allergens have not been completely characterized. Objectives: We sought to identify allergens associated with lupine allergy, evaluate potential cross-reactivity with peanut, and determine eliciting doses (EDs) for lupine allergy by using double-blind, placebo-controlled food challenges. Methods: Six patients with a history of allergic reactions to lupine flour were evaluated by using skin prick tests, CAP tests, and double-blind, placebo-controlled food challenges. Three of these patients were also allergic to peanut. Lupine allergens were characterized by means of IgE immunoblotting and peptide sequencing. Results: In all 6 patients the ED for lupine flour was 3 mg or less for subjective symptoms and 300 mg or more for objective symptoms. The low ED and moderate-to-severe historical symptoms indicate significant allergenicity of lupine flour. Two patients allergic to lupine but not to peanut displayed IgE binding predominantly to approximately 66-kd proteins and weak binding to 14- and 24-kd proteins, whereas patients with peanut allergy and lupine allergy showed weak binding to lupine proteins of about 14 to 21 or 66 kd. Inhibition of binding was primarily species specific. Conclusion: Lupine allergy can occur either separately or together with peanut allergy, as demonstrated by 3 patients who are cosensitized to peanut and lupine. Clinical implications: Lupine flour is allergenic and potentially cross-reactive with peanut allergen, thus posing some risk if used as a replacement for soy flour

Development of ranking system for higher education of Ukraine

A system of determination of university ranking in Ukraine was developed based on the creation of the corresponding methods adequate to the structure, peculiarities and conditions of the Ukrainian universities functioning. A complex of organizational and program-technical means was proposed for collection of the necessary data and determination of university rankings. For specialists in the field of higher education management, those seeking for higher education and employers.Разработана система определения рейтингов университетов Украины, которая основывается на создании определенной методики, адекватной структуре, особенностям и условиям функционирования отечественной высшей школы. Предложен комплекс организационных и программно-технических средств, который применяется при сборе данных и определении оценок рейтингов университетов для специалистов в области управления высшим образованием, а также желающих получить образование и работодателей.Розроблено систему визначення рейтингів університетів України, яка ґрунтується на створенні відповідної методики, адекватної до структури, особливостей та умов функціонування вітчизняної вищої школи. Запропоновано комплекс організаційних і програмно-технічних засобів, що застосовується при збиранні даних та визначенні оцінок рейтингів університетів для фахівців у галузі управління вищою освітою, а також бажаючих отримати освіту та роботодавців

Peanut Can Be Used as a Reference Allergen for Hazard Characterization in Food Allergen Risk Management: A Rapid Evidence Assessment and Meta-Analysis

Regional and national legislation mandates the disclosure of “priority” allergens when present as an ingredient in foods, but this does not extend to the unintended presence of allergens due to shared production facilities. This has resulted in a proliferation of precautionary allergen (“may contain”) labels (PAL) that are frequently ignored by food-allergic consumers. Attempts have been made to improve allergen risk management to better inform the use of PAL, but a lack of consensus has led to variety of regulatory approaches and nonuniformity in the use of PAL by food businesses. One potential solution would be to establish internationally agreed “reference doses,” below which no PAL would be needed. However, if reference doses are to be used to inform the need for PAL, then it is essential to characterize the hazard associated with these low-level exposures. For peanut, there are now published data relating to over 3000 double-blind, placebo-controlled challenges in allergic individuals, but a similar level of evidence is lacking for other priority allergens. We present the results of a rapid evidence assessment and meta-analysis for the risk of anaphylaxis to a low-level allergen exposure for priority allergens. On the basis of this analysis, we propose that peanut can and should be considered an exemplar allergen for the hazard characterization at a low-level allergen exposure. Resumen: La legislación regional y nacional exige la divulgación de alérgenos "prioritarios" cuando están presentes como ingrediente en los alimentos, pero esto no se extiende a la presencia involuntaria de alérgenos debido a instalaciones de producción compartidas. Esto ha dado lugar a una proliferación de etiquetas de precaución para alérgenos ("pueden contener") (PAL) que los consumidores alérgicos a los alimentos suelen ignorar. Se han hecho intentos para mejorar la gestión del riesgo de alérgenos para informar mejor el uso de PAL, pero la falta de consenso ha llevado a una variedad de enfoques regulatorios y a la falta de uniformidad en el uso de PAL por parte de las empresas alimentarias. Una posible solución sería establecer “dosis de referencia” acordadas internacionalmente, por debajo de las cuales no se necesitaría PAL. Sin embargo, si se van a utilizar dosis de referencia para informar la necesidad de PAL, entonces es esencial caracterizar el peligro asociado con estas exposiciones de bajo nivel. Para el maní, ahora hay datos publicados relacionados con más de 3000 desafíos doble ciego controlados por placebo en individuos alérgicos, pero falta un nivel similar de evidencia para otros alérgenos prioritarios. Presentamos los resultados de una evaluación rápida de la evidencia y un metanálisis del riesgo deanafilaxia a una exposición a alérgenos de bajo nivel para alérgenos prioritarios. Sobre la base de este análisis, proponemos que el cacahuete puede y debe considerarse un alérgeno ejemplar para la caracterización del peligro en una exposición a un alérgeno de bajo nivel.Instituto de Investigación de Tecnología de AlimentosFil: Turner, Paul J. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Patel, Nandinee. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Ballmer-Weber, Barbara K. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Ballmer-Weber, Barbara K. Clínica de Dermatología y Alergología. Kantonsspital; Suiza.Fil: Baumert, Joe L. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Blom, W. Marty. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Brooke-Taylor, Simon. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Brough, Helen. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Brough, Helen. King's College London. Departamento de Alergia Pediátrica; Reino Unido.Fil: Campbell, Dianne E. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Campbell, Dianne E. Tecnologías DBV. Montrouge; Francia.Fil: Chen, Hongbing. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Chinthrajah, R. Sharon. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Crevel, René W.R. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Dubois, Anthony E.J. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Ebisawa, Motohiro. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Elizur, Arnon. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Elizur, Arnon. Universidad de Tel Aviv. Facultad de Medicina Sackler. Departamento de Pediatría; Israel.Fil: Gerdts, Jennifer D. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Gowland, M. Hazel. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Houben, Geert F. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Hourihane, Jonathan O.B. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Knulst, André C. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: La Vieille, Sébastien. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: López, María Cristina. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Mills, E.N. Clare. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Polenta, Gustavo Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Tecnología de Alimentos; Argentina.Fil: Polenta, Gustavo Alberto. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Purington, Natasha. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Said, María. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Sampson, Hugh A. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Sampson, Hugh A. Escuela de Medicina Icahn. División de Alergia e Inmunología Pediátricasen. Nueva York. Estados Unidos de América.Fil: Schnadt, Sabine. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Södergren, Eva. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Södergren, Eva. ThermoFisher Scientific; Suecia.Fil: Taylor, Stephen L. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Remington, Benjamin C. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido.Fil: Remington, Benjamin C. Grupo BV. Consultoría Remington; Holanda

Can we define a level of protection for allergic consumers that everyone can accept?

Substantial progress has been made in characterising the risk associated with exposure to allergens in food. However, absence of agreement on what risk is tolerable has made it difficult to set quantitative limits to manage that risk and protect allergic consumers effectively. This paper reviews scientific progress in the area and the diverse status of allergen management approaches and lack of common standards across different jurisdictions, including within the EU. This lack of regulation largely explains why allergic consumers find Precautionary Allergen Labelling confusing and cannot rely on it. We reviewed approaches to setting quantitative limits for a broad range of food safety hazards to identify the reasoning leading to their adoption. This revealed a diversity of approaches from pragmatic to risk-based, but we could not find clear evidence of the process leading to the decision on risk acceptability. We propose a framework built around the criteria suggested by Murphy and Gardoni (2008) for approaches to defining tolerable risks. Applying these criteria to food allergy, we concluded that sufficient knowledge exists to implement the framework, including sufficient expertise across the whole range of stakeholders to allow opinions to be heard and respected, and a consensus to be achieved

Tolerance to alternative cyclooxygenase-2 inhibitors in nonsteroidal anti-inflammatory drug hypersensitive patients

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) frequently cause adverse drug reactions. Many studies have shown that drugs which selectively inhibit the cyclooxygenase-2 enzyme (COX-2) are safe alternatives in the majority of patients. However, hypersensitivity reactions to COX-2 inhibitors have been published. Hardly any data are available regarding the safety of alternatives in case of COX-2 inhibitor hypersensitivity. We aimed to investigate the tolerance to COX-2 inhibitors in patients with non-selective NSAID hypersensitivity. Furthermore, in COX-2 hypersensitive patients tolerance of a second COX-2 inhibitor was investigated. METHODS: We retrospectively analyzed 91 patients with proven non-selective NSAID hypersensitivity that underwent oral challenges with a COX-2 inhibitor. Patients with intolerance to the first challenged COX-2 inhibitor received a second challenge with a different COX-2 inhibitor. RESULTS: 19 out of 91 (21%) patients had a positive reaction to the first oral challenge with a COX-2 inhibitor. 14 of them underwent a second challenge with a different COX-2 inhibitor and 12 (86%) did not react. CONCLUSIONS: A relatively high percentage (21%) of the non-selective NSAID hypersensitive patients did not tolerate a COX-2 inhibitor and oral challenge is advised prior to prescription of a COX-2 inhibitor. For the majority of patients reacting to a COX-2 inhibitor an alternative can be found

Exposure of Intestinal Epithelial Cells to Short- and Long-Chain Fructo-Oligosaccharides and CpG Oligodeoxynucleotides Enhances Peanut-Specific T Helper 1 Polarization

BackgroundNon-digestible oligosaccharides promote colonization of beneficial gut bacteria and have direct immunomodulatory effects. Apical exposure of intestinal epithelial cells (IECs) to short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (scGOS/lcFOS) in a transwell co-culture model enhanced the CpG-induced (TLR-9 ligand) T helper 1 (Th1) phenotype and regulatory IL-10 response of underlying peripheral mononuclear cells (PBMCs) of healthy donors. scGOS is derived from lactose and may pose risks in severe cow’s milk allergic patients, and scFOS/lcFOS may be an alternative. The goal of this study was to determine the immunomodulatory effects of scGOS/lcFOS and scFOS/lcFOS in an allergen-specific transwell co-culture model using PBMCs from peanut-allergic patients.MethodsIECs cultured on transwell filters were apically exposed to CpG, either or not in combination with oligosaccharides. These IECs were co-cultured with basolateral PBMCs of peanut-allergic patients that were either activated with aCD3/28 or peanut extract. Basolateral cytokine production and T-cell polarization were measured and the contribution of galectin-9 and the dectin-1 receptor in immune modulation were assessed.ResultsIECs exposed to CpG increased IFN-γ, IL-10, and galectin-9 production by aCD3/28-stimulated PBMCs, whereas IL-13 decreased. Both scGOS/lcFOS and scFOS/lcFOS further enhanced IFN-γ and IL-10, while suppressing IL-13 and TNF-α. In the peanut-specific model, only scFOS/lcFOS further increased IFN-γ and IL-10 production, coinciding with enhanced Th1-frequency. Expression of CRTH2 reduced after CpG exposure, and was further reduced by scFOS/lcFOS. Galectin-9 inhibitor TIM-3-Fc abrogated the additional effect of scFOS/lcFOS on peanut-specific IFN-γ production, while neutralization of the dectin-1 receptor was not effective.ConclusionEpithelial exposure to scFOS/lcFOS enhanced the CpG-induced Th1 and regulatory IL-10 response in a peanut-specific co-culture model. These effects suggest scFOS/lcFOS as candidate for dietary adjunct in allergen-specific immunotherapy

Exposure of Intestinal Epithelial Cells to Short- and Long-Chain Fructo-Oligosaccharides and CpG Oligodeoxynucleotides Enhances Peanut-Specific T Helper 1 Polarization

Background: Non-digestible oligosaccharides promote colonization of beneficial gut bacteria and have direct immunomodulatory effects. Apical exposure of intestinal epithelial cells (IECs) to short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (scGOS/lcFOS) in a transwell co-culture model enhanced the CpG-induced (TLR-9 ligand) T helper 1 (Th1) phenotype and regulatory IL-10 response of underlying peripheral mononuclear cells (PBMCs) of healthy donors. scGOS is derived from lactose and may pose risks in severe cow's milk allergic patients, and scFOS/lcFOS may be an alternative. The goal of this study was to determine the immunomodulatory effects of scGOS/lcFOS and scFOS/lcFOS in an allergen-specific transwell co-culture model using PBMCs from peanut-allergic patients. Methods: IECs cultured on transwell filters were apically exposed to CpG, either or not in combination with oligosaccharides. These IECs were co-cultured with basolateral PBMCs of peanut-allergic patients that were either activated with aCD3/28 or peanut extract. Basolateral cytokine production and T-cell polarization were measured and the contribution of galectin-9 and the dectin-1 receptor in immune modulation were assessed. Results: IECs exposed to CpG increased IFN-γ, IL-10, and galectin-9 production by aCD3/28-stimulated PBMCs, whereas IL-13 decreased. Both scGOS/lcFOS and scFOS/lcFOS further enhanced IFN-γ and IL-10, while suppressing IL-13 and TNF-α. In the peanut-specific model, only scFOS/lcFOS further increased IFN-γ and IL-10 production, coinciding with enhanced Th1-frequency. Expression of CRTH2 reduced after CpG exposure, and was further reduced by scFOS/lcFOS. Galectin-9 inhibitor TIM-3-Fc abrogated the additional effect of scFOS/lcFOS on peanut-specific IFN-γ production, while neutralization of the dectin-1 receptor was not effective. Conclusion: Epithelial exposure to scFOS/lcFOS enhanced the CpG-induced Th1 and regulatory IL-10 response in a peanut-specific co-culture model. These effects suggest scFOS/lcFOS as candidate for dietary adjunct in allergen-specific immunotherapy

High occurrence of antihistamine resistance in patients with recurrent idiopathic angioedema

Antihistamines are the most prescribed therapy in recurrent idiopathic angioedema, yet little is known about their efficacy. Herein, we report on clinical improvement with antihistamine therapy in 120 patients evaluating angioedema attack frequency. A high incidence (36%) of antihistamine refractory cases was observed. Forty percent of patients on antihistamine prophylaxis suffered from 1 or more angioedema attacks per month. Our findings stress the need for additional treatment options for recurrent idiopathic angioedema

High occurrence of antihistamine resistance in patients with recurrent idiopathic angioedema

Abstract Antihistamines are the most prescribed therapy in recurrent idiopathic angioedema, yet little is known about their efficacy. Herein, we report on clinical improvement with antihistamine therapy in 120 patients evaluating angioedema attack frequency. A high incidence (36%) of antihistamine refractory cases was observed. Forty percent of patients on antihistamine prophylaxis suffered from 1 or more angioedema attacks per month. Our findings stress the need for additional treatment options for recurrent idiopathic angioedema