Inverse relation between structural flexibility and IgE reactivity of Cor a 1 hazelnut allergens
A major proportion of allergic reactions to hazelnuts (Corylus avellana) are caused by immunologic cross-reactivity of IgE antibodies to pathogenesis-related class 10 (PR-10) proteins. Intriguingly, the four known isoforms of the hazelnut PR-10 allergen Cor a 1, denoted as Cor a 1.0401-Cor a 1.0404, share sequence identities exceeding 97% but possess different immunologic properties. In this work we describe the NMR solution structures of these proteins and provide an in-depth study of their biophysical properties. Despite sharing highly similar three-dimensional structures, the four isoforms exhibit remarkable differences regarding structural flexibility, hydrogen bonding and thermal stability. Our experimental data reveal an inverse relation between structural flexibility and IgE-binding in ELISA experiments, with the most flexible isoform having the lowest IgE-binding potential, while the isoform with the most rigid backbone scaffold displays the highest immunologic reactivity. These results point towards a significant entropic contribution to the process of antibody binding.
https://doi.org/10.1038/s41598-021-83705-z
Component-Resolved Diagnosis of Hazelnut Allergy in Children
Hazelnuts commonly elicit allergic reactions starting from childhood and adolescence, with a rare resolution over time. The definite diagnosis of a hazelnut allergy relies on an oral food challenge. The role of component resolved diagnostics in reducing the need for oral food challenges in the diagnosis of hazelnut allergies is still debated. Therefore, three electronic databases were systematically searched for studies on the diagnostic accuracy of specific-IgE (sIgE) on hazelnut proteins for identifying children with a hazelnut allergy. Studies regarding IgE testing on at least one hazelnut allergen component in children whose final diagnosis was determined by oral food challenges or a suggestive history of serious symptoms due to a hazelnut allergy were included. Study quality was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Eight studies enrolling 757 children, were identified. Overall, sensitivity, specificity, area under the curve and diagnostic odd ratio of Cor a 1 sIgE were lower than those of Cor a 9 and Cor a 14 sIge. When the test results were positive, the post-test probability of a hazelnut allergy was 34% for Cor a 1 sIgE, 60% for Cor a9 sIgE and 73% for Cor a 14 sIgE. When the test results were negative, the post-test probability of a hazelnut allergy was 55% for Cor a 1 sIgE, 16% for Cor a9 sIgE and 14% for Cor a 14 sIgE. Measurement of IgE levels to Cor a 9 and Cor a 14 might have the potential to improve specificity in detecting clinically tolerant children among hazelnut-sensitized ones, reducing the need to perform oral food challenges.
https://doi.org/10.3390/nu13020640
Peanut diversity and specific activity are the dominant IgE characteristics for effector cell activation in children
Background: IgE mediates allergic reactions to peanut; however, peanut-specific IgE (sIgE) levels do not always equate to clinical peanut allergy. Qualitative differences between sIgE of peanut sensitized but tolerant (PS) and peanut allergic (PA) individuals may be important.
Objective: To assess the influence of IgE characteristics on effector cell activation in peanut allergy.
Methods: A cohort of 100 children was studied. The levels of IgE to peanut and peanut components were measured. Specific activity (SA) was estimated as the ratio of allergen-sIgE to total IgE. Avidity was measured by ImmunoCAP with sodium thiocyanate. IgE diversity was calculated based on ImmunoCAP-ISAC (Immuno Solid-phase Allergen Chip) assays for 112 allergens or for 6 peanut allergens. Whole blood basophils and mast cell line Laboratory of Allergic Diseases 2 (LAD2) sensitized with patients' plasma were stimulated with peanut or controls and assessed by flow cytometry.
Results: SA to peanut (p<0.001), Ara h 1 (p=0.004), Ara h 2 (p<0.001), Ara h 3 (p=0.02) and Ara h 6 (p<0.001) and the avidity of peanut-sIgE (P<0.001) was higher in PA than in PS individuals. Diversity for peanut allergens was greater in PA individuals (p<0.001). All IgE characteristics were correlated with basophil and mast cell activation. Peanut SA (R=0.447) and PD (R=0.440) had the highest standardized β-coefficients in combined multivariable regression models (0.447 and 0.440, respectively).
Conclusions: IgE specificity, SA, avidity and peanut diversity was statistically different in PA and PS individuals. IgE Peanut SA and PD had the greatest influence on effector cell activation and could be employed clinically.
Oral immunotherapy for peanut allergy: The con argument
Background: In some countries of the world, peanut allergy represents an important source of anaphylactic reactions. Traditionally treated with the avoidance of responsible allergens, this condition can also be targeted by oral peanut immunotherapy.
Methods: In this study, we review the beneficial and side effects of currently available forms of peanut oral immunotherapy (POIT). We report the discussions resulting from the publication of a meta-analysis that brought to light the downsides of oral immunotherapy for peanuts.
Results: In some clinical situations, the risk-benefit ratio can favor peanut oral immunotherapy over avoidance. In many other situations, this is not the case. The decision must be based on the values and preferences of clinicians and patients. Those not ready to accept serious adverse effects from POIT are likely to continue the elimination diet; those motivated to achieving desensitization, and prepared to accept serious adverse effects, may choose to undergo POIT.
Conclusions: Without being prejudiced against peanut oral immunotherapy, we indicate the possible evolution of treatment for this condition is in a rapidly evolving broader scenario. Among the future options, sublingual immunotherapy, parenteral immunotherapy with modified allergens, transcutaneous immunotherapy, and the use of biologics will become important options.
Effect of roasted peanut allergen Ara h 3 protein on the sensitization of Caco-2 cells
Background: Roasted peanut is widely loved as a kind of food with rich taste. However, peanut allergy is one of the major threats to human health, which affects about 5% of children and 1.4-2% of adults in the world.
Results: To evaluate the sensitization mechanism of peanut allergen Ara h 3, Caco-2 cells as the model, which has the similar structure and function to differentiated small intestinal epithelial cells. Compared with Ara h 3-raw (purified from raw peanut) group, more significant results such as the inhibited Caco-2 cell viability and proliferation, the increased secretion of ROS and the decreased transepithelial electrical resistance were obtained in Ara h 3-roasted (purified from roasted peanut) group. Accordingly, oxidative stress and NF-κB signaling pathway were more imbalanced, which lead to the increased of TSLP, IL-6, IL-8 and MCP-1. Then the gene expression of tight junction proteins ZO-1, occludin and JAM-1 were down more, which proved the integrity of Caco-2 monolayer barrier is severely damaged.
Conclusion: These finding identify the mechanisms of the allergenicity of roasted peanut allergy proteins are probably associated with intestinal uptake and cytokinedependent allergies. The aggravated allergic reaction might be caused by the increment of TSLP, IL-6, IL-8 and MCP-1 due to the activated NF-κB signaling pathway, and the enhanced transport of Ara h 3-roasted protein by Caco-2 monolayer.
Antioxidant Capacity and Phenolic and Sugar Profiles of Date Fruits Extracts from Six Different Algerian Cultivars as Influenced by Ripening Stages and Extraction Systems
The study investigated the phenols, sugar and the antioxidant capacities of date fruit extracts obtained by organic solvents and by hydrothermal treatment from six different Algerian cultivars at two ripening stages for the first time. The analyzed cultivars exhibited potent antioxidant properties (ferric reducing antioxidant power (FRAP), 1,1-Diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) scavenging capacities) and different phenols regardless of the solvents and the maturity stages. About 18 phenols were identified and quantified, mainly in the hydrothermal extracts. The earlier stages were characterized by high amounts of o-coumaric acid, cinnamic acid and luteolin, with a noticeable absence of quercetin. The tamr stage presented the highest sugar content (78.15-86.85 mg/100 mg dry weight (DW)) with an abundance of glucose. Galactose was present only in some cultivars from the kimri stage (tamjouhert). Uronic acids were mostly detected at the tamr stage (4.02-8.82 mg gallic acid equivalent/100 mg dried weight). The obtained results highlight the potential of using date fruit extracts as natural antioxidants, especially at industrial scales that tend use hydrothermal extraction.
https://doi.org/10.3390/foods10030503
Bioaccessibility of cashew nut kernel flour compounds released after simulated in vitro human gastrointestinal digestion
Cashew nuts are mainly consumed as a roasted and salted snack. Lately, the industry has gained interest in broken kernels because of their added value. In this study, defatted cashew nut flour (DCF) underwent simulated gastrointestinal digestion to obtain a soluble (CDs) and an insoluble (CDi) digested fraction. These fractions, which resulted from the digestion of a complex matrix, were evaluated for antioxidant capacity of bioaccessible compounds (present on the soluble digested fraction, CDs) and their potential prebiotic effect, considering that the insoluble digested fraction (CDi) could be fermented by the microbiota in the gut. The DCF had a high protein content (40.74%), being nutritionally characterized as a balanced source of amino acids, with a predominance of aromatic amino acids (phenylalanine and tyrosine), threonine and histidine. The digested DCF presented 76.90% of the soluble components of low molecular weight (0.1-2 kDa), which is typical of antioxidant peptides. The soluble digested fraction (CDs) significantly increased the antioxidant capacity in relation to flour in the ORAC and ABTS assays and the aqueous extract presented the highest values (526.0 and 76.64 as µmol Trolox Eq./g sample, respectively). The CDs protected 29.03% of the supercoiled DNA band and ratified the potential antioxidant capacity after GID in a physiological assay. In addition, the insoluble digested fraction showed a potential prebiotic effect for Bifdobacterium lactis BB-12. Finally, simulated gastrointestinal digestion improves the bioaccessibility of CDF antioxidant compounds as a complex matrix, containing low molecular weight peptides and phenolic compounds, which become more available to react with reactive oxygen species (ROS). In addition, the potential prebiotic effect of defatted cashew nut flour has yielded a promising solution for the total reuse of broken cashew nut kernel as a functional food ingredient.
Giffonins, Antioxidant Diarylheptanoids from Corylus avellana, and Their Ability to Prevent Oxidative Changes in Human Plasma Proteins
With the aim to explore the ability of diarylheptanoids to reduce oxidative changes in human plasma proteins, a phytochemical investigation of the MeOH extract of Corylus avellana leaves was perfomed. Analysis by LC-ESI/LTQOrbitrap/MS/MSn guided the isolation of two new diarylheptanoid derivatives, giffonins W (1) and X (2). The structures 1 and 2 were assigned by analysis of NMR data combined with a QM (quantum mechanical)/NMR approach. The absolute configurations of 1 and 2 were established by analysis of electronic circular dichroism (ECD) spectra compared with the TDDFT-simulated curves. The antioxidant activity of the new and known giffonins was evaluated by inhibition of human plasma lipid peroxidation. Giffonins with the highest inhibitory activity were tested for their ability to reduce oxidation of thiol groups and carbonylation in plasma proteins, and some of them exhibited higher antioxidant activity than curcumin.
Socioeconomic and lifestyle factors modifies the association between nut consumption and metabolic syndrome incidence
Background & aims: The aim of this study was to evaluate the association of nut consumption and its various types with metabolic syndrome (MetS) risk and to investigate whether lifestyle factors (physical activity and smoking status) and socioeconomic status (education and occupation) modulate the association of nut consumption and the risk of MetS.
Methods: We prospectively studied 1915 participants of the Tehran Lipid and Glucose study, among whom 591 were diagnosed with MetS during 8.9 years of follow-up. Nut consumption and its various types were assessed using a validated semi-quantitative food frequency questionnaire. Multivariable adjusted Cox regression was used to estimate Hazard Ratios (HRs) for MetS events across tertiles of nut consumption and its various types. Regarding interaction between nut consumption and physical activity levels, education levels, and smoking status on the risk of MetS, using joint classification, the effect modification of lifestyle factors and socioeconomic status on the association between nut consumption (<median and ≥ median) and risk of MetS was assessed by Cox regression.
Results: Nut consumption was inversely associated with MetS risk in multivariable-adjusted models. The highest tertiles of the constituents of nuts including fiber, polyphenol, MUFA and PUFA reduced MetS risk compared with the lowest tertiles, after adjustment for confounders. Among various types of nuts, the multivariable-adjusted HRs of MetS were 0.78 (0.63-0.96) for walnuts, and 0.77 (0.63-0.94) for pistachios, compared with the lowest intake. Among adult population, consuming nuts higher than the median and having moderate to high physical activity levels resulted in significant reduction in the MetS risk (HRs: 0.74, CI: 0.55-0.98 for moderate and HRs: 0.63, CI: 0.47-0.86 for high physical activity level). Participants who did not smoke had lower risk of MetS regardless of their amount of nuts consumption (HRs: 0.67, CI: 0.47-0.94 for intakes < median and HRs: 0.71, CI: 0.53-0.93 for intakes ≥ median). Stratification based on education status resulted in reduction in the risk of MetS in participants consuming nuts ≥ median in both educated and not-educated group (HRs: 0.81, CI: 0.66-0.98 for the non-educated group and HRs: 0.63, CI: 0.47-0.84 for the educated group).
Conclusions: Incorporating nuts, especially walnuts, into dietary patterns reduced the risk of MetS, especially among individuals with more physical activity levels.
The Hull of Ripe Pistachio Nuts (Pistacia vera L.) as a Source of New Promising Melanogenesis Inhibitors
In the present study an acidified methanol pistachio hull extract was investigated for antioxidant and inhibitory effects on melanin biosynthesis by in vitro and in vivo assays. The chromatographic analysis revealed that cyanidin-3-O-galactoside represents the main compound (98.37%). The pistachio hull extract efficiently inhibits the mono and diphenolase activity of mushroom tyrosinase (IC50= 141.07 and 116.08 μg/mL, respectively) and it was able, thanks to its strong antioxidant and free-radical scavenging activities, to hinder the L-DOPA auto-oxidation in a concentration-dependent manner (125-500 μg/mL). Results of in vivo assay showed that the treatment with pistachio hull extract (10 μg/mL) reduced pigmentation in zebrafish embryos at early stages of development (60.01% of inhibition vs control). In conclusion, these findings suggest that the ripe pistachio hull may be considered as a promising source of antioxidant and skin whitening agents for the development of new products useful in preventing the pigmentation disorders in humans and/or to improve the food quality.