New dietary trends and alternative proteins: the emergence of novel food allergens.

Purpose Of Review: New dietary trends driven by environmental and health considerations will undoubtedly lead to the emergence of novel food allergens. Assessment of the allergenic risk of new or modified protein-containing food sources and ingredients, as well as surveillance of emerging food allergies, is then required.

Recent Findings: Developments of in silico and in vitro models apprehending protein capacity to cross-react with other homologous proteins and to induce a de novo allergic sensitization are ongoing to better integrate multiple parameters such as 3D structural information or major histocompatibility complex class II (MHC-II) presentation propensity.

Allergenicity assessment of new or modified protein-containing food sources and ingredients.

The growing world population, changing dietary habits, and increasing pressure on agricultural resources are drivers for the development of novel foods (including new protein sources as well as existing protein sources that are produced or used in an alternative way or in a different concentration). These changes, coupled with consumer inclination to adopt new dietary trends, may heighten the intake of unfamiliar proteins, or escalate consumption of specific ones, potentially amplifying the prevalence of known and undiscovered food allergies. Assessing the allergenicity of novel or modified protein-based foods encounters several challenges, including uncertainty surrounding acceptable risks and assessment criteria for determining safety.

Immunotherapy-induced neutralizing antibodies disrupt allergen binding and sustain allergen tolerance in peanut allergy.

In IgE-mediated food allergies, exposure to the allergen activates systemic allergic responses. Oral immunotherapy (OIT) treats food allergies through incremental increases in oral allergen exposure. However, OIT only induces sustained clinical tolerance and decreased basophil sensitivity in a subset of individuals despite increases in circulating allergen-specific IgG in all treated individuals.

Allergen Risk Assessment for Specific Allergy to Small Ruminant's Milk: Development of Sensitive Immunoassays to Detect Goat's and Sheep's Milk Contaminations in Dairy Food Matrices.

Despite a high level of sequence identity between cow's, goat's, and sheep's milk (CM, GM, and SM, respectively) proteins, some patients tolerant to CM are allergic to GM and SM. In most cases, this specificity is due to the presence of IgE antibodies that bind only to caprine and ovine caseins. The patients may then develop severe allergic reactions after ingestion of CM products contaminated with low amounts of GM or SM.

The Effector Function of Allergens.

Allergens are antigens that generate an IgE response (sensitization) in susceptible individuals. The allergenicity of an allergen can be thought of in terms of its ability to sensitize as well as its ability to cross-link IgE/IgE receptor complexes on mast cells and basophils leading to release of preformed and newly formed mediators (effector activity). The identity of the allergens responsible for sensitization may be different from those that elicit an allergic response.

Route of Sensitization to Peanut Influences Immune Cell Recruitment at Various Mucosal Sites in Mouse: An Integrative Analysis.

Symptom occurrence at the first ingestion suggests that food allergy may result from earlier sensitization via non-oral routes. We aimed to characterize the cellular populations recruited at various mucosal and immune sites after experimental sensitization though different routes. BALB/cJ mice were exposed to a major allergenic food (peanut) mixed with cholera toxin via the intra-gastric (i.

Immunodominant conformational and linear IgE epitopes lie in a single segment of Ara h 2.

Background: Contribution of conformational epitopes to the IgE reactivity of peanut allergens Ara h 2 and Ara h 6 is at least as important as that of the linear epitopes. However, little is known about these conformational IgE-binding epitopes.

Objective: We investigated the distribution of conformational epitopes on chimeric 2S-albumins.

Sensitization Potency of Sunflower Seed Protein in a Mouse Model: Identification of 2S-Albumins More Allergenic Than SFA-8.

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.

Administration of Extensive Hydrolysates From Caseins and GG Probiotic Does Not Prevent Cow's Milk Proteins Allergy in a Mouse Model.

Background: Early nutrition may influence the development of food allergies later in life. In the absence of breastfeeding, hydrolysates from cow's milk proteins (CMP) were indicated as a prevention strategy in at risk infants, but their proof of effectiveness in clinical and pre-clinical studies is still insufficient. Thanks to a validated mouse model, we then assessed specific and nonspecific preventive effects of administration of extensive hydrolysates from caseins (eHC) on the development of food allergy to CMP.

Prevention of Allergy to a Major Cow's Milk Allergen by Breastfeeding in Mice Depends on Maternal Immune Status and Oral Exposure During Lactation.

The high incidence of food allergy in childhood points to the need of elucidating early life factors dictating allergy susceptibility. Here, we aim to address in a mouse model how the exposure to a major cow's milk allergen through breastmilk of mothers with different immune status influences food allergy outcome in offspring. BALB/cJ future dams were either kept naïve, or sensitized through the oral route using cholera toxin ("orally sensitized") or through the i.

Variable IgE cross-reactivity between peanut 2S-albumins: The case for measuring IgE to both Ara h 2 and Ara h 6.

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.

Deep analysis of immune response and metabolic signature in children with food protein induced enterocolitis to cow's milk.

Background: Food Protein-Induced Enterocolitis Syndrome (FPIES) is considered to be a non-IgE mediated food allergy. However, its pathogenesis remains poorly understood and biomarkers are lacking. We aimed to perform in-depth characterization of humoral and cellular immune responses in children with cow's milk (CM)-FPIES and investigated whether there is a FPIES metabolomic signature.

Intragastric administration of Lactobacillus casei BL23 induces regulatory FoxP3+RORγt+ T cells subset in mice.

Many studies have highlighted the immunomodulatory properties of the probiotic strain Lactobacillus casei BL23. Recently, we demonstrated the ability of this strain to modulate the Th2-oriented immune response in a mouse model of cow's milk allergy based on the induction of a Th17-biased immune response. The probiotic function of L.

Odd Chain Fatty Acids; New Insights of the Relationship Between the Gut Microbiota, Dietary Intake, Biosynthesis and Glucose Intolerance.

Recent findings have shown an inverse association between circulating C15:0/C17:0 fatty acids with disease risk, therefore, their origin needs to be determined to understanding their role in these pathologies. Through combinations of both animal and human intervention studies, we comprehensively investigated all possible contributions of these fatty acids from the gut-microbiota, the diet, and novel endogenous biosynthesis. Investigations included an intestinal germ-free study and a C15:0/C17:0 diet dose response study.

Neonatal mono-colonization of germ-free mice with Lactobacillus casei enhances casein immunogenicity after oral sensitization to cow's milk.

Scope: Food allergy is an increasing global health problem and perinatal administration of probiotic bacteria is currently under investigation in order to prevent the development of allergic diseases. Here, we investigated the impact of neonatal mono-colonization of mice with Lactobacillus casei BL23 on an oral sensitization to cow's milk.

Methods And Results: Mono-colonized (LC) mice were obtained by inoculating L.

Heat processing of peanut seed enhances the sensitization potential of the major peanut allergen Ara h 6.

Scope: Processing of food has been shown to impact IgE binding and functionality of food allergens. In the present study, we investigated the impact of heat processing on the sensitization capacity of Ara h 6, a major peanut allergen and one of the most potent elicitors of the allergic reaction.

Methods And Results: Peanut extracts obtained from raw or heat-processed peanut and some fractions thereof were biochemically and immunochemically characterized.

Allergenicity of peanut component Ara h 2: Contribution of conformational versus linear hydroxyproline-containing epitopes.

Background: The 2S-albumin Ara h 2 is the most potent peanut allergen and a good predictor of clinical reactivity in allergic children. Posttranslational hydroxylation of proline residues occurs in DPYSP(OH)S motifs, which are repeated 2 or 3 times in different isoforms.

Objectives: We investigated the effect of proline hydroxylation on IgE binding and the relative contributions of linear and conformational epitopes to Ara h 2 allergenicity.

Goat's milk allergy without cow's milk allergy: suppression of non-cross-reactive epitopes on caprine β-casein.

Background And Objective: Goat's milk (GM) allergy associated with tolerance to cow's milk (CM) has been reported in patients without history of CM allergy and in CM-allergic children successfully treated with oral immunotherapy. The IgE antibodies from GM-allergic/CM-tolerant patients recognize caprine β-casein (βcap) without cross-reacting with bovine β-casein (βbov) despite a sequence identity of 91%. In this study, we investigated the non-cross-reactive IgE-binding epitopes of βcap.

Delayed bacterial colonization of the gut alters the host immune response to oral sensitization against cow's milk proteins.

Scope: Cow's milk allergy is the most prevalent food allergy in infants whose immune system development is critically stimulated during postnatal gut colonization by commensal bacteria. Allergenic potential of cow's milk β-lactoglobulin (BLG) and caseins (CAS) was investigated in germ-free (GF) BALB/c mice and in GF mice conventionalized (CVd) at 6 weeks of age.

Methods And Results: Oral sensitization to cow's milk in the presence of cholera toxin led to higher BLG-specific IgE, IgG1, and IgG2a responses in GF mice than in conventional (CV) mice.

Specificity of IgE antibodies from patients allergic to goat's milk and tolerant to cow's milk determined with plasmin-derived peptides of bovine and caprine β-caseins.

Scope: Despite a sequence homology of 90% between bovine and caprine β-caseins (CN), IgE antibodies from patients allergic to goat's milk (GM), but tolerant to cow's milk (CM), recognize caprine β-CN without cross-reacting with bovine β-CN. We investigated this lack of cross-reactivity by evaluating the IgE-reactivity toward peptides isolated from plasmin hydolysates of bovine and caprine β-CN.

Methods And Results: The IgE-binding capacity of plasmin-derived peptides was evaluated with sera from 10 CM-allergic patients and 12 GM-allergic/CM-tolerant patients.

Trypsin resistance of the major peanut allergen Ara h 6 and allergenicity of the digestion products are abolished after selective disruption of disulfide bonds.

Scope: 2S-albumins Ara h 2 and Ara h 6 are the most widely recognized and potent allergens for peanut-allergic patients. These allergens are particularly resistant to proteolysis and the digestion products generally retain significant allergenicity. Five disulfide bridges (DB) stabilize Ara h 6 overall structure and their influence on the trypsin resistance and on the allergenicity of the digestion products was investigated.

Allergenic and immunogenic potential of cow's milk β-lactoglobulin and caseins evidenced without adjuvant in germ-free mice.

Scope: In most animal models of allergy, the development of an IgE response requires the use of an adjuvant. Germ-free (GF) mice exhibit Th2-polarized antibody responses combined with defective immunosuppressive mechanisms. The sensitizing potential of milk proteins was investigated in GF mice in the absence of adjuvant.