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

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

Fructo-Oligosaccharides Modify Human DC Maturation and Peanut-Induced Autologous T-Cell Response of Allergic Patients In Vitro

Background: Dendritic cells (DCs) play an important role in antigen presentation, and are an interesting target for immune-modulation in allergies. Short- and long-chain fructo-oligosaccharides (scFOS/lcFOS, FF) have immunomodulatory capacities, and may influence the outcome of DC antigen presentation. Objective: This study investigated the effect of FF during DC maturation and allergen presentation using cells of peanut-allergic patients in an autologous DC-T cell assay. Methods: CD14+ and CD4+ T cells were isolated from peanut-allergic patients. CD14+ monocytes were differentiated into immature DCs (imDCs), and matured (matDCs) in the presence or absence of crude peanut-extract (CPE) and/or FF, and co-cultured in an autologous DC-T cell assay. T cell polarization, proliferation and cytokine production were measured. Results: Expression of maturation surface molecule markers on matDCs was not affected by CPE and/or FF. By contrast, the IL-10 secretion by matDCs increased compared to imDCs, upon exposure to CPE and FF compared to CPE alone. Also the IP-10 secretion increased in CPE/FF-matDCs compared to imDC. CPE-matDCs enhanced IL-13 release in the DC-T-cell assay and Treg polarization in presence or absence of FF. CPE/FF-DCs tended to increase the Treg/Th1 and Treg/Th2 ratios compared to matDCs. The proliferation of both Treg and Th2 cells tended to increase when T cells were co-cultured with CPE-matDCs compared to matDCs, which became significant when CPE-matDCs were also exposed to FF and a same tendency was shown for Th1 proliferation. Conclusion: Only in the presence of FF, CPE-matDCs produced increased regulatory and Th1-related mediators. CPE-matDCs modified T cell polarization and proliferation, and additional exposure to FF tended to enhance Treg/Th2 and Treg/Th1 ratios instructed by CPE/FF-matDCs. However this effect was not strong enough to suppress CPE-matDCs induced IL-13 release by Th-cells. This indicates the ability of FF to modify DC maturation in the presence of an allergen supporting a more Treg/Th1 prone direction of the successive allergen specific Th2 cell response

Hazelnut allergy: from pollen-associated mild allergy to severe anaphylactic reactions

PURPOSE OF REVIEW: Hazelnut allergy can vary between mild oral symptoms and potentially dangerous anaphylaxis. There is a need to predict which subjects are at risk for severe reactions. In this study, possibilities for 'component-resolved diagnosis', based on sensitization to different allergens in hazelnut, are discussed. RECENT FINDINGS: One type of hazelnut allergy can be associated with sensitization to homologues of pollen allergens, predominantly birch, in hazelnut: Cor a 1 (Bet v 1) and Cor a 2 (profilin). These allergens account for relatively mild symptoms. However, subjects can also be sensitized to several other allergens in hazelnut that are related to more severe symptoms. These allergens are homologues of allergens in other nuts and peanut: Cor a 8 (lipid transfer protein) and Cor a 9 (11S globulin) and perhaps Cor a 11 (7S globulin). The clinical relevance of these and other potential hazelnut allergens has to be further defined. The diagnosis of hazelnut has to be confirmed by oral double-blind placebo-controlled food challenge. SUMMARY: Sensitization to hazelnut can either be associated with mild oral symptoms, depending on sensitization to pollen, or with more serious allergic symptoms, related to sensitization to homologues of nut and peanut allergen