Background
2S‐albumins Ara h 2 and Ara h 6 are the most potent peanut allergens and levels of specific immunoglobulin E (IgE) towards these proteins are good predictors of clinical reactivity. ...Because of structural homologies, Ara h 6 is generally considered to cross‐react extensively with Ara h 2.
Objective
We aimed to quantify the IgE cross‐reactivity between Ara h 2 and Ara h 6.
Methods
Peanut 2S‐albumins were purified from raw peanuts. The IgE cross‐reactivity between Ara h 2 and Ara h 6 was evaluated with 32 sera from French and US peanut‐allergic patients by measuring the residual IgE‐binding to one 2S‐albumin after depletion of IgE antibodies recognizing the other 2S‐albumin. The IgE cross‐reactivity between Ara h 2 and Ara h 6 was further investigated by competitive inhibition of IgE‐binding and by a model of mast cell degranulation.
Results
A highly variable level of IgE cross‐reactivity was revealed among the patients. The mean fraction of cross‐reactive IgE antibodies represented only 17.1% of 2S‐albumins‐specific IgE antibodies and was lower than the mean fraction of IgE specific to Ara h 2 (57.4%) or to Ara h 6 (25.5%). The higher level of Ara h 2‐specific IgE was principally due to the IgE‐binding capacity of an insertion containing the repeated immunodominant linear epitope DPYSPOHS. The impact of IgE cross‐reactivity on diagnostic testing was illustrated with a serum displaying an Ara h 6‐specific IgE response of 26 UI/mL that was not associated with the capacity of Ara h 6 to trigger mast cell degranulation.
Conclusions & Clinical Relevance
Immunoglobulin E antibodies specific to peanut 2S‐albumins are mainly non–cross‐reactive, but low‐affinity cross‐reactivity can affect diagnostic accuracy. Testing IgE‐binding to a mixture of 2S‐albumins rather than to each separately may enhance diagnostic performance.
Microbial metabolism of specific dietary components, such as fiber, contributes to the sophisticated inter‐kingdom dialogue in the gut that maintains a stable environment with important beneficial ...physiological, metabolic, and immunological effects on the host. Historical changes in fiber intake may be contributing to the increase of allergic and hypersensitivity disorders as fiber‐derived metabolites are evolutionarily hardwired into the molecular circuitry governing immune cell decision‐making processes. In this review, we highlight the importance of fiber as a dietary ingredient, its effects on the microbiome, its effects on immune regulation, the importance of appropriate timing of intervention to target any potential window of opportunity, and potential mechanisms for dietary fibers in the prevention and management of allergic diseases. In addition, we review the human studies examining fiber or prebiotic interventions on asthma and respiratory outcomes, allergic rhinitis, atopic dermatitis, and overall risk of atopic disorders. While exposures, interventions, and outcomes were too heterogeneous for meta‐analysis, there is significant potential for using fiber in targeted manipulations of the gut microbiome and its metabolic functions in promoting immune health.
Identification and specific quantification of isomers in a complex biological matrix by mass spectrometry alone is not an easy task due to their identical chemical formula and therefore their same ...mass‐to‐charge ratio (m/z). Here, the potential of direct introduction combined with ion mobility–mass spectrometry (DI‐IM‐MS) for rapid quantification of isomers as human milk oligosaccharides (HMOs) was investigated. Differences in HMO profiles between various analyzed breast milk samples were highlighted using the single ion mobility monitoring (SIM2) acquisition for high ion mobility resolution detection. Furthermore, the Se+ (secretor) or Se− (non‐secretor) phenotype could be assigned to breast milk samples studied based on their HMO contents, especially on the response of 2′‐fucosyllactose (2’‐FL) and lacto‐N‐fucopentaose I (LNFP I). The possibility of quantifying a specific isomer in breast milk by DI‐IM‐MS was also investigated. The standard addition method allowed the determination of the 2’‐FL despite the presence of other oligosaccharides, including 3‐fucosyllactose (3‐FL) isomer in breast milk. This proof‐of‐concept study demonstrated the high potential of such an approach for the rapid and convenient quantification of isomers in complex mixtures.
Oligosaccharides have multiple functions essential for health. Derived from the condensation of two to several monosaccharides, they are structurally diverse with many co‐occurring structural isomer ...families, which make their characterization difficult. Thanks to its ability to separate small molecules based on their mass, size, shape, and charge, ion mobility‐mass spectrometry (IM‐MS) has emerged as a powerful tool for separating glycan isomers. Here, the potential of such a technique for the rapid characterization of main human milk oligosaccharides (HMOs) was investigated. Our study focused on 18 HMO standards. The IM‐MS analysis enabled to distinguish almost all the HMOs studied, in particular thanks to the single ion mobility monitoring acquisition using the trapped ion mobility spectrometry device, providing high ion mobility resolution and enhanced ion mobility separation. Alternatively, the combination of IM‐MS separation with MS/MS experiments has proven to increase performance in identifying HMOs and especially isomers poorly separated by ion mobility alone. Finally, collision cross‐section values are provided for each species generated from the 18 HMOs standards, which can serve as an additional identifier to characterize HMOs.
Scope
Food allergy to sunflower seed (SFS) protein is not frequent and only non‐specific lipid transfert protein (nsLTP) Hel a 3 is officially recognized as a food allergen. Out of the eleven seed ...storage 2S‐albumins (SESA) detected in SFS, only SFA‐8 allergenicity has been investigated so far. The study aimed then to evaluate SFS protein allergenicity and particularly, to compare the sensitization potency of SESA in a mouse model.
Methods and Results
The most abundant SESA and nsLTP were isolated from SFS through a combination of chromatographic methods. Purified proteins were then used to measure specific IgG1 and IgE responses in BALB/c mice orally sensitized to different SFS protein isolates. The study, thus, confirmed the allergenicity of SFA‐8 and Hel a 3 but mice were also highly sensitized to other SESA such as SESA2‐1 or SESA20‐2. Furthermore, competitive inhibition of IgE‐binding revealed that SFA‐8 IgE‐reactivity was due to cross‐reactivity with other SESA. 11S‐globulins were weakly immunogenic and were rapidly degraded in an in vitro model of gastroduodenal digestion. In contrast, Hel a 3, SESA2‐1 and SFA‐8 were more resistant to proteolysis and gastroduodenal digestion did not affect their IgE‐reactivity.
Conclusions
SESA2‐1 or SESA20‐2 were more potent allergens than SFA‐8 in this mouse model. Allergenicity of SESA must be now confirmed in SFS‐allergic patients.
Allergy to sunflower seed is not frequent but non‐specific lipid transfert protein Hel a 3 and 2S‐albumin SFA‐8 are already known allergens. De novo sensitization to seed storage 2S‐albumins (SESA) was compared in a mouse model. IgE‐sensitization was evidenced for various SESA but IgE‐reactivity of
SFA‐8 was due to cross‐reactivity with other SESA. SESA allergenicity must be now assessed in food‐allergic patients.
Background
Food allergy (FA) is an inappropriate immunological response to food proteins resulting from an impaired induction of oral tolerance. Various early environmental factors can affect the ...establishment of intestinal homeostasis, predisposing to FA in early life. In this context, we aimed to assess the effect of chronic perinatal exposure to food‐grade titanium dioxide (fg‐TiO2), a common food additive.
Methods
Dams were fed a control versus fg‐TiO2‐enriched diet from preconception to weaning, and their progeny received the same diet at weaning. A comprehensive analysis of baseline intestinal and systemic homeostasis was performed in offspring 1 week after weaning by assessing gut barrier maturation and microbiota composition, and local and systemic immune system and metabolome. The effect of fg‐TiO2 on the susceptibility of progeny to develop oral tolerance versus FA to cow's milk proteins (CMP) was performed starting at the same baseline time‐point, using established models. Sensitization to CMP was investigated by measuring β‐lactoglobulin and casein‐specific IgG1 and IgE antibodies, and elicitation of the allergic reaction by measuring mouse mast cell protease (mMCP1) in plasma collected after an oral food challenge.
Results
Perinatal exposure to fg‐TiO2 at realistic human doses led to an increased propensity to develop FA and an impaired induction of oral tolerance only in young males, which could be related to global baseline alterations in intestinal barrier, gut microbiota composition, local and systemic immunity, and metabolism.
Conclusions
Long‐term perinatal exposure to fg‐TiO2 alters intestinal homeostasis establishment and predisposes to food allergy, with a clear gender effect.
This study investigates the effect of chronic perinatal exposure to food‐grade titanium dioxide (fg‐TiO 2), a common food additive. Chronic perinatal exposure to food‐grade TiO2 (E171) at realistic human doses led to an increased propensity to develop food allergy and an altered induction of oral tolerance in male progeny. Chronic perinatal exposure to E171 alters the establishment of the different components of intestinal homeostasis in early life in male progeny, that is, epithelial barrier function, immune system maturation, and microbiota composition, associated with the alteration of systemic immunity and metabolism.Abbreviations: Actb, actin beta; Actc1, actin alpha cardiac muscle 1; Actn2, actin alpha 2; cDC, conventional dendritic cells; Ctnna1, catenin 1; fg‐TiO2, food‐grade titanium dioxide; Jcad, junctional cadherin 5 associated; mMCP1, mouse mast cell protease; NK, natural killer; Ocln, occludin; Th, T helper.
Background
The new European regulations require the enrichment of formulas with docosahexaenoic acid (DHA) because of the positive effects of long‐chain polyunsaturated fatty acids (LCPUFAs) on ...neurodevelopment and visual acuity. In this observational study, we aimed to evaluate whether the consumption of LCPUFA‐enriched formula was associated with the risk of infection and allergy in early childhood.
Methods
Analyses involved data from 8389 formula‐fed infants from the ELFE birth cohort. Formula enrichment was identified from the list of ingredients of the formula consumed at 2 months. Infections (gastrointestinal, lower respiratory tract LRTI, upper respiratory tract) and allergies (wheezing, itchy rash, asthma medication, food allergy) from age 2 months to 5.5 years were reported by parents during follow‐up surveys. Multivariable logistic regression models were used to assess associations between the consumption of LCPUFA‐enriched formula and the risk of infection and allergy.
Results
Among formula‐fed infants at 2 months, 36% consumed formula enriched with DHA and arachidonic acid (ARA), and 11% consumed formula additionally enriched with eicosapentaenoic acid (EPA). Enriched formula consumption was not associated with infection or allergy, except for an association between consumption of DHA/ARA/EPA‐enriched formula and lower use of asthma medications. Furthermore, as compared with non‐DHA/ARA/EPA‐enriched formula, consumption of formula with high EPA content (≥3.2 mg/100 kcal) was related to lower risk of LRTI and lower use of asthma medications.
Conclusion
This study suggests that consumption of DHA/ARA/EPA‐enriched formula (especially those with high EPA content) is associated with a lower risk of LRTI and lower use of asthma medications.
Among formula‐fed infants at 2 months, 36% consumed DHA/ARA‐enriched formula, and 11% consumed formula additionally enriched with EPA. DHA/ARA/EPA‐enriched formula consumption (especially with high EPA content) was associated with a lower risk of LRTI and lower use of asthma medications up to 5.5 years. DHA/ARA/EPA‐enriched formula consumption was not associated with gastrointestinal infection, wheezing, itchy rash, and food allergy.Abbreviations: ARA, arachidonic acid; DHA, docosahexaenoic acid; ELFE, birth cohort (Étude longitudinale française depuis l’enfance); EPA, eicosapentaenoic acid; LCPUFA, long‐chain polyunsaturated fatty acids; LRTI, lower respiratory tract infection; OR, odds ratio.
IgE-mediated food allergies are caused by adverse immunologic responses to food proteins. Allergic reactions may present locally in different tissues such as skin, gastrointestinal and respiratory ...tract and may result is systemic life-threatening reactions. During the last decades, the prevalence of food allergies has significantly increased throughout the world, and considerable efforts have been made to develop curative therapies. Food allergen immunotherapy is a promising therapeutic approach for food allergies that is based on the administration of increasing doses of culprit food extracts, or purified, and sometime modified food allergens. Different routes of administration for food allergen immunotherapy including oral, sublingual, epicutaneous and subcutaneous regimens are being evaluated. Although a wealth of data from clinical food allergen immunotherapy trials has been obtained, a lack of consistency in assessed clinical and immunological outcome measures presents a major hurdle for evaluating these new treatments. Coordinated efforts are needed to establish standardized outcome measures to be applied in food allergy immunotherapy studies, allowing for better harmonization of data and setting the standards for the future research. Several immunological parameters have been measured in food allergen immunotherapy, including allergen-specific immunoglobulin levels, basophil activation, cytokines, and other soluble biomarkers, T cell and B cell responses and skin prick tests. In this review we discuss different immunological parameters and assess their applicability as potential outcome measures for food allergen immunotherapy that may be included in such a standardized set of outcome measures.
Background and objectives
Partially hydrolyzed formulas (pHF) are recommended in non‐breastfed infants with familial history of allergy to prevent allergy development. However, recent meta‐analysis ...does not provide strong support for their protective effect. The present work assesses the links between 2‐month infant formula use and the incidence of eczema, respiratory symptoms, or food allergies (FA) up to 2 years of age.
Methods
The nationwide ELFE birth cohort is a population‐based study from mainland France. Infant feeding (breast milk only, partially hydrolyzed formula with pHF‐HA or without a hypoallergenic label pHF‐non‐HA, and non‐hydrolyzed formula Nhf) was reported at 2 months. Eczema, FA, and respiratory symptoms such as wheezing and asthma were reported at 2 months, 1 year, and 2 years. Infants with prior FA at 2 months were excluded from analyses.
Results
Among 11 720 infants, those who received only breast milk at 2 months were at lower risk of eczema at 1 year than those who received nHF (OR95% CI = 0.780.65‐0.94 in non‐at‐risk infants; 0.860.75‐0.98 in at‐risk infants). The use of pHF‐HA, compared with nHF, at 2 months was related to higher risk of wheezing at 1 year in at‐risk infants (1.681.24‐2.28) and higher risk of FA at 2 years both in non‐at‐risk infants (3.781.52‐9.41) and in at‐risk infants (2.311.36‐3.94).
Conclusions
In this nationwide study, pHF‐HA use was not associated with a lower risk of any of the studied outcomes. Quite the reverse, it was associated with a higher risk of wheezing and FA. This should be confirmed in further studies.
Background
Bioaccessibility of food allergens may be a key determinant of allergic reactions.
Objective
To develop a protocol allowing the detection of the major peanut allergen, Ara h 6, in the ...bloodstream following ingestion of low amounts of peanut and to compare Ara h 6 bioaccessibility by food matrix. We further assessed for differences in absorption in healthy versus peanut‐allergic volunteers.
Methods
A blood pretreatment combining acidic shock and thermal treatment was developed. This protocol was then applied to blood samples collected from human volunteers (n = 6, healthy controls; n = 14, peanut‐allergic patients) at various time‐points following ingestion of increasing levels of peanut incurred in different food matrices (cookies, peanut butter and chocolate dessert). Immunodetection was performed using an in‐house immunoassay.
Results
An original pretreatment protocol was optimized, resulting in irreversible dissociation of human antibodies‐Ara h 6 immune complex, thus rendering Ara h 6 accessible for its immunodetection. Ara h 6 was detected in samples from all volunteers following ingestion of 300‐1000 mg peanut protein, although variations in the kinetics of passage were observed between individuals and matrices. Interestingly, in peanut‐allergic subjects, Ara h 6 could be detected following ingestion of lower doses and at higher concentrations than in non‐allergic volunteers.
Conclusions and Clinical Relevance
The kinetics and intensity of Ara h 6 passage in bloodstream depend on both individual and food matrix. Peanut‐allergic patients appear to demonstrate higher absorption rate, the clinical significance of which warrants further evaluation.
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