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IgE-mediated food allergy is characterized immunologically by a type 1 immune response triggered upon exposure to specific foods and clinically by a broad range of manifestations and variable severity. Our understanding of food allergy within the allergic march of atopic dermatitis (AD) is still incomplete despite the related risk of unpredictable and potentially severe associated reactions such as anaphylactic shock. The aim of this pilot study was to investigate the effects of dupilumab, an IL-4/IL-13 monoclonal antibody approved for AD, on the allergic sensitization profile of patients with AD and type 1 hypersensitivity-related comorbidities, including oral allergy syndrome, anaphylaxis, and gastrointestinal disorders. We conducted an observational pilot study with a longitudinal prospective design, enrolling 20 patients eligible for treatment with dupilumab. Laboratory exams for total serum IgE, specific IgE, and molecular allergen components were performed at baseline and after 16 weeks of therapy. Our results demonstrate a statistically significant decrease in molecular components, specific IgE for trophoallergens, and specific IgE for aeroallergens following treatment with dupilumab. We suggest that modulating type 2 immunity may decrease IgE-mediated responses assessed with laboratory exams and therefore could minimize allergic symptoms in polysensitized patients. Upcoming results of randomized controlled trials investigating dupilumab in food allergy are highly anticipated to confirm its potential effect in the treatment of IgE-mediated food allergies.

Background: There are increasing numbers of metabolomic studies in food allergy (FA) and asthma, which, however, are predominantly limited by cross-sectional designs, small sample size, and being conducted in European populations., Objective: We sought to identify metabolites unique to and shared by children with FA and/or asthma in a racially diverse prospective birth cohort, the Boston Birth Cohort., Methods: Mass spectrometry-based untargeted metabolomic profiling was performed using venous plasma collected in early childhood (n = 811). FA was diagnosed according to clinical symptoms consistent with an acute hypersensitivity reaction at food ingestion and food specific-IgE > 0.35 kU/L. Asthma was defined on the basis of physician diagnosis. Generalized estimating equations were applied to analyze metabolomic associations with FA and asthma, adjusting for potential confounders., Results: During a mean ± standard deviation follow-up of 11.8 ± 5.2 years from birth, 78 children developed FA and 171 developed asthma. Androgenic and pregnenolone steroids were significantly associated with a lower risk of FA, especially for egg allergy. N,N,N-trimethyl-5-aminovalerate (odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.48-0.87), and 1-oleoyl-2-arachidonoyl-sn-glycero-3-phosphoinositol (OR = 0.77; 95% CI = 0.66-0.90) were inversely associated with FA risk. Orotidine (OR = 4.73; 95% CI = 2.2-10.2) and 4-cholesten-3-one (OR = 0.52; 95% CI = 0.35-0.77) were the top 2 metabolites associated with risk of asthma, although they had no association with FA. In comparison, children with both FA and asthma exhibited an altered metabolomic profile that aligned with that of FA, including altered levels of lipids and steroids., Conclusion: In this US multiethnic prospective birth cohort, unique and shared alterations in plasma metabolites during early childhood were associated with risk of developing FA and/or asthma. These findings await further validation., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: Eosinophilic esophagitis (EoE) is associated with atopy; however, recent studies have identified an association with food-specific immunoglobulin G 4 (FS-IgG 4 ) rather than immunoglobulin E antibodies. This study aimed to evaluate the role of serum FS-IgG 4 in guiding an elimination diet and its outcomes., Methods: Patients with and without EoE were enrolled in a prospective, controlled, single tertiary center trial. Serum FS-IgG 4 titers, esophageal eosinophil counts, and dysphagia symptom questionnaire scores were assessed, and participants with elevated FS-IgG 4 (ImmunoCAP, cutoff of 10 mgA/L) commenced 6-week targeted elimination diet. Repeat serum FS-IgG 4 and endoscopic and histologic examination were performed at 6-week follow-up., Results: Twenty-two patients with active EoE and 13 controls were recruited. Serum FS-IgG 4 to milk, wheat, soy, eggs, and nuts was significantly higher in EoE ( P = 0.0002, P = 0.002, P = 0.003, P = 0.012, and P < 0.001, respectively). Elevated serum FS-IgG 4 to 1 or more food groups (median 2) was identified in 21/22 (95.4%) patients with EoE; 20/21 underwent 6-week dietary elimination. Median reductions in dysphagia symptom questionnaire score and EoE endoscopic reference score after elimination were 8 ( P = 0.0007) and 1 ( P = 0.002), respectively. Nine (45%) patients had histological remission (<15 eosinophils per high-power field). Fall in median esophageal eosinophil count was not statistically significant (50 vs 23; P = 0.068). Serum FS-IgG 4 did not decline by 6-week follow-up., Discussion: Serum FS-IgG 4 to milk, wheat, soy, egg, and nuts was present at higher levels in EoE, with targeted elimination resulting in 45% histologic remission rate. Serum FS-IgG 4 has potential as a noninvasive biomarker in EoE. When successful, FS-IgG 4 -led elimination diet can negate need for medications and be viewed more favorably by patients because of its smaller endoscopic burden compared with empirical elimination diets., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy characterized by profuse vomiting within hours of ingestion of the causative food. We have previously reported that FPIES is associated with systemic innate immune activation in the absence of a detectable antigen-specific antibody or T-cell response. The mechanism of specific food recognition by the immune system remains unclear., Objective: Our aim was to identify immune mechanisms underlying FPIES reactions by proteomic and flow cytometric analysis of peripheral blood., Methods: Children with a history of FPIES underwent supervised oral food challenge. Blood samples were taken at baseline, at symptom onset, and 4 hours after symptom onset. We analyzed samples from 23 children (11 reactors and 12 outgrown). A total of 184 protein markers were analyzed by proximity ligation assay and verified by multiplex immunoassay. Analysis of cell subset activation was performed by mass cytometry and spectral cytometry., Results: Symptomatic FPIES challenge results were associated with significant elevation of levels of cytokines and chemokines, including IL-17 family markers (IL-17A, IL-22, IL-17C, and CCL20) and T-cell activation (IL-2), and innate inflammatory markers (IL-8, oncostatin M, leukemia inhibitory factor, TNF-α, IL-10, and IL-6). The level of the mucosal damage marker regenerating family member 1 alpha (REG1A) was also significantly increased. These biomarkers were not increased in asymptomatic challenges or IgE-mediated allergy. The level of phospho-STAT3 was significantly elevated in myeloid and T cells after challenge in individuals with symptoms. Mass cytometry indicated preferential activation of nonconventional T-cell populations, including γδ T cells and CD3 + CD4 - CD8 - CD161 + cells; however, the potential sources of IL-17 in PBMCs were primarily CD4 + T H 17 cells., Conclusions: These results demonstrate a unique IL-17 signature and activation of innate lymphocytes in FPIES., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Roasting is known to affect the protein profile and allergenicity of hazelnuts (Corylus avellana cv TGL). The aim of the study was to investigate whether roasting techniques based on different heat transfer methods (hot air and infrared), differently affect the protein solubility and the IgE-binding capacities of both the soluble and insoluble hazelnut protein fractions. The immune-reactivity of the Cor a 9, Cor a 11 and Cor a 14 allergens resulted to be stable after roasting at 140 °C, for both types of treatment, while roasting at 170 °C caused a reduction in IgE-binding, which was particularly noticeable after infrared processing, that led to an almost complete disappearance of allergenicity. Microscopical analyses showed that roasting caused cytoplasmic network disruption, with a loss of lipid compartmentalization, as well as an alteration of the structure of the protein bodies and of the cell wall organization., (Copyright © 2020. Published by Elsevier Ltd.)

Background: IgE to α-Gal is a cause of mammalian meat allergy and has been linked to tick bites in North America, Australia, and Eurasia. Reports from the developing world indicate that α-Gal sensitization is prevalent but has been little investigated., Objective: We sought evidence for the cause(s) of α-Gal sensitization and lack of reported meat allergy among children in less developed settings in Ecuador and Kenya., Methods: IgE to α-Gal and total IgE were assessed in children from Ecuador (n = 599) and Kenya (n = 254) and compared with children with (n = 42) and without known (n = 63) mammalian meat allergy from the southeastern United States. Information on diet, potential risk factors, and helminth infections was available for children from Ecuador. IgG 4 to α-Gal and antibodies to regionally representative parasites were assessed in a subset of children., Results: In Ecuador (32%) and Kenya (54%), α-Gal specific IgE was prevalent, but levels were lower than in children with meat allergy from the United States. Sensitization was associated with rural living, antibody markers of Ascaris exposure, and total IgE, but not active infections with Ascaris or Trichuris species. In Ecuador, 87.5% reported consuming beef at least once per week, including 83.9% of those who had α-Gal specific IgE. Levels of α-Gal specific IgG 4 were not high in Ecuador, but were greater than in children from the United States., Conclusions: These results suggest that in areas of the developing world with endemic parasitism, α-Gal sensitization is (1) common, (2) associated with Ascaris exposure, and (3) distinguished by a low percentage of specific/total IgE compared with individuals with meat allergy in the United States., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: Immunoglobulin E (IgE) to galactose-α-1,3-galactose (alpha-gal) is a recently appreciated cause of allergic reactions to mammalian meat and dairy. In eastern North America Lone Star tick bites are the dominant mode of sensitization. Classically the alpha-gal syndrome manifests with urticaria, gastrointestinal symptoms, and/or anaphylaxis, but increasingly there are reports of isolated gastrointestinal symptoms without other common allergic manifestations. The objective of this retrospective study was to determine the frequency of IgE to alpha-gal in patients presenting with unexplained gastrointestinal symptoms to a community gastroenterology practice, and to evaluate the symptom response to the removal of mammalian products from the diet in alpha-gal-positive individuals., Methods: An electronic medical record database was used to identify patients with alpha-gal IgE laboratory testing performed within the past 4 years. These charts were reviewed for alpha-gal test results, abdominal pain, diarrhea, nausea and vomiting, hives, bronchospasm, diagnosis of irritable bowel syndrome, postprandial exacerbation of symptoms, meat exacerbation of symptoms, patient recall of tick bite, other simultaneous gastrointestinal tract diagnoses, and clinical improvement with mammalian food product avoidance., Results: A total of 1112 adult patients underwent alpha-gal IgE testing and 359 (32.3%) were positive. Gastrointestinal symptoms were similar in those positive and negative for alpha-gal seroreactivity. Of the 359 alpha-gal-positive patients, 122 had follow-up data available and 82.0% of these improved on a diet free of mammalian products. Few patients reported hives (3.9%) or bronchospasm (2.2%). Serum alpha-gal IgE titers ranged from 0.1 to >100 kU/L, with an average of 3.43 kU/L and a median of 0.94 kU/L., Conclusions: Clinicians practicing in the region of the Lone Star tick habitat need to be aware that patients with IgE to alpha-gal can manifest with isolated abdominal pain and diarrhea, and these patients respond well to dietary exclusion of mammalian products.

Background: Immunoglobulin E (IgE) mediated food allergy is a potentially life-threatening condition and represents a heavy burden for patients and their families. Identification of the most suitable way for management of each patient has currently become the primary goal for physicians. Methods: This study reviewed the current literature related to IgE-mediated food allergy. Results: The use of innovative diagnostic tools, such as allergen-specific IgG4 determination, basophil activation test, and component-resolved diagnostics, is currently available to facilitate a proper diagnosis of food allergy. After several decades of "passive clinical management" of the disease, which was based only on avoidance of the allergenic food and the use of epinephrine in the event of anaphylaxis, there has been a switch to active treatment. The most recent evidence-practice guidelines strongly recommend the use of immunotherapy as an effective therapeutic option, particularly in cases of allergy to cow's milk, egg, or peanut. The use of omalizumab, in association with immunotherapy or alone, has been tested in several studies, and results on its effectiveness seemed to be encouraging. Other biologics, such as dupilumab, reslizumab, mepolizumab, and other anticytokines therapies, are being investigated. Another interesting future treatment strategy could be the use of DNA vaccines. Conclusion: In recent years, the management of IgE-mediated food allergy has greatly improved. Knowledge of pathogenetic mechanisms, understanding of the disease course, and the introduction of novel biomarkers led to more accurate diagnoses along with the active treatment of patients.

Food allergy is an antigen-specific immunological adverse reaction after exposure to a given food. Multiple clinical studies showed that oral immunotherapy (OIT) is effective for the prevention and treatment for food allergy that is developed in infants and children. However, the effectiveness of OIT for epicutaneously sensitized food allergy remains unclear. Previously, we established a mouse model of epicutaneous-sensitized food allergy. In this model, systemic allergic reaction including intestinal and skin symptoms, such as anaphylaxis, was observed. We treated this model with OIT in two ways (OIT before sensitization or OIT during the sensitization phase) and evaluated the preventive effect of both methods. OIT before sensitization significantly ameliorated mast cell degranulation in sensitized skin, but there was no decrease in rectal temperatures or in mast cell degranulation in the jejunum. However, OIT administered during the sensitization phase significantly ameliorated the decrease in rectal temperature and mast cell degranulation in the skin and jejunum. OIT before sensitization increased the regulatory T cells in mesenteric lymph node (MLN), but not in the spleen, and it reduced antigen-specific IgG, but not IgE, production compared with the non-OIT control. However, OIT during sensitization caused a greater increase in regulatory T cells in both the MLN and spleen and reduced antigen-specific IgE and IgG generation compared with the non-OIT control group. Thus, OIT during the sensitization phase was effective for the prevention of epicutaneous-sensitized food allergy., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Food allergy (FA) has become an increasing problem throughout the world. Over the last 2 decades, the frequency of FA has increased in both children and adults. The prevalence differs according to the research methodology, age, and geographic regions, ranging between 2.0% and 10.0%. The most common form of FA is immunoglobulin E (IgE)-mediated FA. In this form, patients may present with life-threatening conditions, such as anaphylaxis, or milder conditions, such as urticaria, angioedema, sneezing, and nausea alone. The gold standard in the diagnosis of FA is oral provocation tests. Epidermal skin prick tests and specific IgE measurements, as well as component-resolved diagnostic techniques are helpful in the diagnosis and follow-up of patients. In this review, the epidemiology, diagnosis, follow-up, and prognosis of IgE-mediated FA in children and adults were discussed and some specific forms of FA, such as pollen FA syndrome, alpha-gal allergy, and food-dependent exercise-induced anaphylaxis were explained., Competing Interests: The authors declare no conflicts of interest., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Background: The role of serum S100A8/A9 in intestinal inflammation has been confirmed, and its role in food allergy is currently being investigated., Objective: To explore the levels of S100A8/A9 and inflammatory factors, including Toll-like receptors 4 (TLR4), Nuclear transcription factors (NF-κB) and Tumor necrosis factor α (TNF-α), in mild food allergies., Methods: Eighty 3-week-old male Brown Norway rats were used. Forty rats were randomly assigned to the ovalbumin-sensitized experimental group, while 40 rats were assigned to the normal saline sham-sensitized control group. Body weight and length and the levels of serum ovalbumin-specific IgE (OVA-IgE), histamine, Th1-associated and Th2-associated factors, S100A8/A9 and inflammation-associated cytokines were compared., Results: Through the evaluation of OVA-IgE level and Th1/Th2 balance in the experimental group, a successful IgE-mediated food allergy model was constructed. Compared with the control group, the experimental group had higher serum S100A8/A9 levels on days 21, 28, 35 and 42 (all P < 0.05); higher TLR4 levels on days 28, 35 and 42 (all P < 0.05); higher TNF-α levels on days 28, 35 and 42 (all P < 0.05); higher NF-κB levels on days 35 and 42 (all P < 0.05); and higher IL-1β and IL-6 levels on days 7 to 42 (all P < 0.05). Moreover, positive correlations were found between the serum levels of S100A8/A9 and inflammation-associated cytokines [TNF-α: r = 0.378, P = 0.039; IL-1β: r = 0.679, P = 0.000; IL-6: r = 0.590, P = 0.001]., Conclusion: S100A8/A9 and inflammatory-related factors, including TLR4, NF-κB, TNF-α, IL-6 and IL-1β, is closely related to food allergies. Moreover, immune and inflammatory factors interact with each other in food allergies, which may provide insight into food allergy causes and treatments.

Lipopolysaccharide (LPS)-binding protein (LBP) is an acute-phase reactant that mediates innate immune responses triggered by LPS. Recent studies indicated a positive correlation of circulating LBP level with chronic low-grade inflammation, a condition present in many non-communicable diseases. We determined the association of serum LBP concentration with allergic sensitization in a general pediatric population. Serum LBP was measured in a sample of children (n = 356; mean age = 9.6 ± 0.2 years) in this population-based cross-sectional study. Skin prick tests (SPTs) were performed to assess allergic sensitization to 22 common inhalant and food allergens. One hundred and seven children (30.1%) were nonsensitized, 160 (44.9%) were monosensitized, and 89 (25.0%) were polysensitized. Children who were mono- or polysensitized had a significantly higher median serum LBP level (25.5 ng/mL, inter-quartile range [IQR] 20.3-30.7) than those who were nonsensitized (20.3 ng/mL, IQR = 14.81-25.8, P < 0.0001). Multivariate logistic regression analysis with adjustment for confounders indicated that serum LBP level was positively associated with allergic sensitization overall (adjusted odds ratio [aOR] 1.041; 95% CI 1.007-1.076, P = 0.016), with sensitization to food allergens in particular (aOR 1.080, 95% CI 1.029-1.133, P = 0.002), but not with sensitization to aeroallergens (aOR 1.010, 95% CI 0.982-1.040, P = 0.467). LBP level was not associated with allergic diseases after adjustment. We suggest the possibility of sensitization to food allergens may be related to gut-derived low-grade inflammation, and large sized longitudinal investigations are needed to elucidate the relationship.

Background: Omalizumab has been shown to improve the safety and feasibility of oral immunotherapy (OIT), but the optimal dosage strategy is unknown., Objective: Our aim was to identify determinants of omalizumab dose-related efficacy in the context of OIT., Methods: The study sample consisted of a clinical cohort of 181 patients treated with omalizumab-enabled oral immunotherapy at 3 centers. Patients received omalizumab for at least 2 months before an initial food escalation (IFE) with a mix of up to 6 allergens. Progression through IFE steps was assessed with survival analysis. Continued food dose tolerance with omalizumab weaning was also documented., Results: Omalizumab dosage per weight alone was strongly associated with progression through the IFE (χ 2  = 28.18; P < .0001), whereas the standard dosage per weight and total IgE level used for asthma was not (χ 2  = 0.001; P = .97). When the values at time of IFE were estimated through pharmacokinetics and pharmacodynamics simulation, IFE outcome was best predicted by a model that includes levels of free allergen-specific IgE and their interaction with blocking omalizumab-IgE complexes and free omalizumab levels in serum (χ 2  = 65.84; degrees of freedom [df] = 2; P < .0005). The occurrence of immediate-type reactions to food dosing subsequent to weaning of omalizumab was associated with a greater ratio of specific IgE level to total IgE level at baseline (geometric mean 0.39 vs 0.16 in those without symptom; P < .0001)., Conclusion: In the context of OIT and IgE-mediated disease, omalizumab dosages should be adjusted for body weight alone, independently of total IgE level. The fraction of allergen-specific/total IgE may be useful to predict patients at greater risk of food dosing reactions subsequent to weaning., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Introduction: Cross-reactivity between shrimp and house dust mite (HDM) proteins has been widely documented. In tropical region, shrimp (5-15%) and mite sensitization (80-95%) is prevalent in allergic patients. However, the clinical relevance of shrimp sensitization in patients with allergic rhinitis (AR) has been poorly studied. The aim of this study was to determine the prevalence and the clinical relevance shrimp IgE sensitization in AR patients sensitized to Dermatophagoides pteronyssinus., Methods: The study was conducted in Medellin (Colombia). A cross-sectional study in patients with AR sensitized to HDM was performed in 3 steps: (i) assessment of IgE sensitization frequency to shrimp Penaeus azteca, Litopenaeus vannamei, and tropomyosin homologous allergens rDer p 10, rPen a 1, and rLit v 1, (ii) evaluation of the clinical relevance of shrimp sensitization using oral challenge test (OCT) and (iii) identification of possible risk factors for positive-OCT results. Ethical committee approval was obtained., Results: From 443 patients with AR, 86 (19.4%) were sensitized to shrimp and 23 of them (26.7%) had shrimp allergy diagnosis. Thirty-six of the patients sensitized to shrimp (41.2%) reported not previously consumed this food and eleven of them had a positive-OCT (30.5%). There was not statistically significant difference in total IgE or sIgE (D. pteronyssinus, P. azteca, L. vannamei, rPen a 1, and rLit v 1) between OCT groups (positive vs. negative results). Anti-Der p 10 IgE was associated with risk for a positive-OCT in different multivariable scenarios., Discussion/conclusion: Our results suggest that in patients with HDM-associated AR and shrimp IgE sensitization is necessary to evaluate the clinical relevance of shrimp IgE even if the patient has never consumed shrimp because of cross-reactivity. Anti-Der p 10 could be a possible biomarker of clinical relevance to shrimp sensitization and could reduce the need for OCTs., (© 2021 S. Karger AG, Basel.)

Basophil activation tests (BATs) can closely monitor, in vitro , a patient's propensity to develop type I hypersensitivity reactions. Because of their high specificity and sensitivity, BATs have become promising diagnostic tools, especially in cases with equivocal clinical histories, skin prick test results, and/or levels of specific IgE to allergen extracts. BATs also are useful as tools for monitoring the effects of treatment, since oral immunotherapy (OIT) studies report a diminution in patients' basophil responsiveness over the course of OIT. This review will discuss the BAT findings obtained before, during, and after OIT for food allergy. We will mainly focus on the association of basophil responsiveness, and alterations in basophil surface markers, with clinical outcomes and other clinical features, such as blood levels of specific IgG and IgE antibodies. The detailed analysis of these correlations will ultimately facilitate the use of BATs, along with other blood biomarkers, to differentiate short-term desensitization versus sustained unresponsiveness and to improve treatment protocols. Given the critical anatomic location of mast cells adjacent to the many IgE + plasma cells found in the gastrointestinal tissues of allergic individuals, we will also discuss the role of gastrointestinal mast cells in manifestations of food allergies., Competing Interests: SG reports grants from NIH. RC reports grants from NIAID, CoFAR, Aimmune, DBV Technologies, Astellas, Regeneron, is an Advisory member for Alladapt, Genentech, Novartis, and receives personal fees from Before Brands outside the submitted work. KN reports grants from NIAID, NHLBI, NIEHS, Food Allergy Research & Education (FARE); other funding from World Allergy Organization (WAO), Cour Pharma, Before Brands, Alladapt, Latitude, IgGenix, Immune Tolerance Network (ITN), and NIH clinical research centers outside the submitted work. In addition, KN has the following patents pending: Inhibition of Allergic Reaction to Peanut Allergen using an IL-33 Inhibitor; Special Oral Formula for Decreasing Food Allergy Risk and Treatment for Food Allergy; Basophil Activation Based Diagnostic Allergy Test; Granulocyte-based methods for detecting and monitoring immune system disorders; Methods and Assays for Detecting and Quantifying Pure Subpopulations of White Blood Cells in Immune System Disorders; Mixed Allergen Compositions and Methods for Using the Same; Microfluidic Device and Diagnostic Methods for Allergy Testing Based on Detection of Basophil Activation. SB has consulted for Regeneron, Sanofi and Novartis on topics unrelated to this study, owns shares in AbCellera and CareDx, and has patents awarded or submitted related to immunoglobulin gene and protein analysis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer EK declared a past co-authorship with several of the authors RSC and KN to the handling editor., (Copyright © 2020 Paranjape, Tsai, Mukai, Hoh, Joshi, Chinthrajah, Nadeau, Boyd and Galli.)

Food allergy is a major health issue, affecting the lives of 8% of U.S. children and their families. There is an urgent need to identify the environmental and endogenous signals that induce and sustain allergic responses to ingested allergens. Acute reactions to foods are triggered by the activation of mast cells and basophils, both of which release inflammatory mediators that lead to a range of clinical manifestations, including gastrointestinal, cutaneous, and respiratory reactions as well as systemic anaphylaxis. Both of these innate effector cell types express the high affinity IgE receptor, FcϵRI, on their surface and are armed for adaptive antigen recognition by very-tightly bound IgE antibodies which, when cross-linked by polyvalent allergen, trigger degranulation. These cells also express inhibitory receptors, including the IgG Fc receptor, FcγRIIb, that suppress their IgE-mediated activation. Recent studies have shown that natural resolution of food allergies is associated with increasing food-specific IgG levels. Furthermore, oral immunotherapy, the sequential administration of incrementally increasing doses of food allergen, is accompanied by the strong induction of allergen-specific IgG antibodies in both human subjects and murine models. These can deliver inhibitory signals via FcγRIIb that block IgE-induced immediate food reactions. In addition to their role in mediating immediate hypersensitivity reactions, mast cells and basophils serve separate but critical functions as adjuvants for type 2 immunity in food allergy. Mast cells and basophils, activated by IgE, are key sources of IL-4 that tilts the immune balance away from tolerance and towards type 2 immunity by promoting the induction of Th2 cells along with the innate effectors of type 2 immunity, ILC2s, while suppressing the development of regulatory T cells and driving their subversion to a pathogenic pro-Th2 phenotype. This adjuvant effect of mast cells and basophils is suppressed when inhibitory signals are delivered by IgG antibodies signaling via FcγRIIb. This review summarizes current understanding of the immunoregulatory effects of mast cells and basophils and how these functions are modulated by IgE and IgG antibodies. Understanding these pathways could provide important insights into innovative strategies for preventing and/or reversing food allergy in patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Kanagaratham, El Ansari, Lewis and Oettgen.)

Introduction and Objectives: Although food allergy is recognized as a growing worldwide public health problem, there continues to be limited data on prevalence rates in developing and emerging countries. Most prevalence estimates are based on self-reports, with only few studies using objective assessments. The aim was to analyze the frequency of sensitization to food allergens by serum specific IgE in a large group of unselected allergic patients in Mexico., Materials and Methods: We analyzed data registries from patients of all ages with suspected food allergy referred to a specialized laboratory in Mexico City from January 2016 to April 2018. A descriptive analysis, and an age/food-group comparison were made., Results: A total of 2633 subjects tested for food allergy were identified during the study period; 1795 subjects fulfilled the inclusion criteria. The overall positivity (sIgE≥0.35kUA/L) to at least one food was 24%. The most frequently positive foods were hazelnut, apple, shrimp, peanut, egg white, egg yolk, peach, almond, tomato, bean, milk, strawberry, kiwi, maize and wheat. Positivity for some foods was more frequent across different age groups, in young children (≤5 years) milk; in older children (6-17 years): peanut, almond, wheat, soy and maize; in adults: apple. We also found other foods with high positivity but less than 50 samples: rye 60%, mango 42.9%, carrot 37.5%, cashew 27.3%, banana 21.1% and oat 20.6%., Conclusion: Our study reported the presence of a differential regional IgE sensitization pattern as compared with the internationally reported one, highlighting the importance of local staple foods., (Copyright © 2020 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Alpha-gal is an oligosaccharide implicated in delayed anaphylaxis following red meat consumption. Exposure to tick bites has been correlated with development of an allergic response to alpha-gal. However, evidence prospectively linking exposure to a single tick species and an immune response to alpha-gal is lacking., Methods: We used serum samples from a prior study cohort of outdoor workers in North Carolina, USA, with high exposure to the lone star tick, Amblyomma americanum, to prospectively evaluate the relationship between tick bites and anti-alpha-gal IgE antibodies., Results: Individuals who reported exposure to one or more tick bites were significantly more likely to have a positive change in anti-alpha-gal IgE compared to individuals with no reported tick bites. This relationship was not dependent on time. A trend toward increasing number of tick bites and increased anti-alpha-gal IgE levels was observed but not statistically significant., Conclusion: To our knowledge, this is the first study to prospectively link documented exposure to A. americanum bites and increased sensitization to alpha-gal in a cohort of outdoor workers. Our results support the role of A. americanum as likely agents for eliciting an allergic response to red meat, and highlight the importance of preventing tick bites.

Introduction and Objectives: Methemoglobinemia has been reported to be associated with severe food protein-induced enterocolitis syndrome (FPIES). However, no reports have evaluated methemoglobin (MHb) levels in FPIES without symptomatic methemoglobinemia or the usefulness of MHb measurement for the diagnostic prediction of FPIES. To evaluate the MHb levels of patients with neonatal-onset FPIES and determine whether MHb levels are higher in FPIES than in other gastrointestinal diseases., Patients and Methods: Eleven neonates with severe acute FPIES (FPIES group) and 139 neonates with other gastrointestinal diseases (non-FPIES group) were included in this study. Patient characteristics, symptoms, and venous blood test values (MHb, pH, HCO 3 - , and C-reactive protein) were evaluated., Results: The median age at onset was 16 days vs. 1 day; males comprised 64% vs. 46%, the median gestational age was 38 weeks vs. 38 weeks, the median birth weight was 2710g vs. 2880g, and the median hospitalization duration was 31 days vs. 6 days for the FPIES vs. non-FPIES groups, respectively. MHb (%) was higher in the FPIES group than in the non-FPIES group [median (range), 1.1 (0.6-10.9) and 0.6 (0.3-1.2), respectively, p<0.001]. There were no differences in terms of pH, HCO 3 - , and C-reactive protein (p>0.05). In the receiver operating characteristic analysis for FPIES diagnosis based on MHb (%), the area under the curve was 0.885, specificity was 97.1%, and sensitivity was 72.7% at a MHb cutoff of 1.0., Conclusion: High MHb levels may help diagnose severe acute FPIES in neonates, but careful evaluation is needed., (Copyright © 2020 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Maternal diet has significant effects on development of childhood atopic disease and hypersensitivity development. However, the gestational dysfunctions demanding special diets are becoming a widespread phenomenon, their immunological implications can be manifested in the profile of antibodies in the offspring's serum., Methods: 153 allergic and 150 healthy individuals were diagnosed for allergy using specific antibody and cytokine immunoassay tests. The medical history of subjects along with mothers' course of pregnancy was completed by allergologist's anamnesis. A self-organizing neural network and multivariate analyses to complex data and pick basic interactions were used., Results: Two significant explanatory modules were determined. The first was formed by gestational diabetic and cholestatic diet, infant formula feeding type, probiotic supplementation and its BMI index, moderate IgE, increased IgG levels of antibodies and single or poly-food allergy type (7 clusters). The second was formed by gestational vegan/vegetarian and elimination diet, maternal probiotic supplementation, sex, high IgE total antibodies and food and mixed poly-allergy to aero- and food-origin allergens (19 clusters)., Conclusions: Significant associations were observed between special gestational diet intake underlying foetal programming and the mechanisms of childhood allergy. The novelty is the positive association between diabetic and cholestatic diet intake and IgE/IgG-mediated food hypersensitivity.

Background: Severe allergy to fruits mediated by a 7 kDa allergen belonging to the gibberellin-regulated protein (GRP) family is known to be associated with Cupressaceae pollinosis., Objective: To identify and characterize Cupressaceae pollen allergens involved in GRP-related fruit allergy., Methods: Pru p 7-related proteins from pollen of Cupressus sempervirens, Juniperus ashei and Cryptomeria japonica were identified using a rabbit anti-Pru p 7 antiserum, purified chromatographically and sequenced by mass spectrometry and bioinformatic comparisons. The C sempervirens protein was produced as a recombinant allergen in Pichia pastoris. IgE antibody binding to pollen GRP proteins was analysed in a peach allergic (n = 54) and a cypress pollen allergic (n = 88) patient population from southern France using ImmunoCAP., Results: In each of the three Cupressaceae species studied, a 7 kDa pollen protein related to Pru p 7 was identified and found to comprise an amino acid sequence of 63 residues in length, 92%-98% identical to each other and 67%-68% identical to Pru p 7. The C sempervirens, J ashei and C japonica GRP allergens have been officially recognized by the WHO/IUIS Allergen Nomenclature Sub-Committee and named Cup s 7, Jun a 7 and Cry j 7, respectively. Recombinant Cup s 7 showed IgE antibody binding capacity comparable to that of the purified natural allergen. Among 51 peach allergic subjects sensitized to Pru p 7, substantially higher levels of IgE to Cup s 7 than to Pru p 7 were found. Further, the pollen protein was able to completely outcompete IgE binding to Pru p 7, while the reverse competition effect was modest, consistent with primary sensitization by the pollen allergen., Conclusion and Clinical Relevance: Pru p 7-related pollen allergens from three Cupressaceae species have been characterized and may become useful for the identification of pollinosis patients at risk of developing severe fruit allergy., (© 2020 John Wiley & Sons Ltd.)

Background: Fatty acids have been implicated in early life immune development. Food allergy provides a clear phenotype of early allergic disease. Fish oil and vitamin D have immune-modulating properties. We aimed to identify the metabolomic profile of (i) infant food allergy and (ii) factors linked to food allergy in past studies such as fish oil supplementation and serum 25OHD3 levels in early life., Methods: NMR was used to quantify 73 metabolites in plasma of 1 year old infants from the Barwon Infant Study (n=485). Logistic regression models were used to examine associations between infant metabolome and food allergy in infants. Linear regression models were used to describe associations between maternal fish oil supplementation and 25OHD3 levels with infant metabolites., Results: A higher linoleic acid: total fatty acid (FA) ratio and phenylalanine level were associated with higher odds of food allergy. Antenatal fish oil supplementation was positively associated with docosahexaenoic acid (DHA) and omega-3 related metabolite levels. Postnatal 25OHD3 levels at 1 year of age were positively associated with several FA measures and creatinine and inversely with the saturated FA: total FA ratio. Only the postnatal 25OHD3 patterns persisted after adjustment for multiple comparisons., Conclusions: Infants with food allergy had altered fatty acid profiles at one year. Fish oil supplementation in pregnancy was associated with higher DHA and omega-3 related metabolites at 1 year of age. Associations were modest and the most robustly altered metabolomic profiles were with postnatal 25OHD3 levels., Competing Interests: Declaration of Competing Interest We declare that we have no competing interests., (Copyright © 2020. Published by Elsevier Ltd.)

Atopic dermatitis (AD) is a common chronic relapsing inflammatory skin disease associated with a personal or family history of atopic diseases. Determining the objective severity scoring of AD index (SCORAD) and total immunoglobulin E (IgE) to help to stage the severity (lesions extent and intensity of the lesions and then the itch and sleep disturbance they may cause) of AD in children.In this study, we adopted the SCORAD index, which consists of severity, area, and sleep disturbance, to evaluate the AD status of children up to 18 years old. We examined the blood levels of total serum IgE, white blood cell count/differential count (WBC/DC), eosinophil counts (EC), eosinophil cationic protein (ECP) and specific IgE.A total of 208 children with AD were enrolled in this study. Serum IgE values and a number of specific IgE that are positive significantly different SCORAD index through simple linear regression; however, after multiple linear regression, only IgE values (95% CI: 0.001-0.004, P < .001), total WBC count (95% CI: 0.112-1.736, P = .026), EC (95% CI: 0.045-6.706, P = .047), and specific IgE to Cheddar cheese (95% CI: 1.814-16.731, P = .015) remain different. After applying the Phi coefficient, we found that specific IgE to tuna (r = 0.632), codfish (r = 0.613), and clam (r = 0.613) each had a moderate correlation with specific IgE to Cheddar cheese. The 6 most common allergens were found to be mite (D. Farinae: 65.9%), mite (D. Pterony: 64.9%), house dust (47.6%), cockroach mix (37.0%), shrimp (30.8%), and crab (22.6%). Covariates of SCORAD index, severity, area, and sleep disturbance differed.In this study, we found that total IgE values, specific IgE values, WBC, EC, and specific IgE to Cheddar cheese have significant correlations with SCORAD index in AD of Taiwanese children.

Purpose of Review: Is to highlight the recent advances in the diagnosis and management of non-IgE-mediated food allergy which is a common consideration in primary care and in allergy and gastroenterology subspecialty practices evaluating infants., Recent Findings: The review focuses on food protein-induced enterocolitis syndrome (FPIES) and includes other non-IgE-mediated food allergy in nursing infants, food protein-induced allergic proctocolitis, and food protein-induced enteropathy. For FPIES, we review the 2017 International Consensus Guidelines that provided the first comprehensive framework for its diagnosis and management and that were supplemented by a 2019 position paper by the European Academy of Allergy and Clinical Immunology. We review recent reports that support FPIES as a diagnosis of primarily infants, highlight the problem of delayed diagnosis, reveal the need for improved biomarkers, emphasize new and common food protein triggers, and identify new approaches for evaluation of tolerance., Summary: As formal diagnostic criteria for non-IgE-mediated food allergies are defined and prevalence data is increasingly reported, there will likely be improved recognition and evaluation of these conditions. Currently, large-scale prospective studies evaluating their incidence and prevalence, associated risk factors, and natural history are needed. Although avoidance of the suspected trigger food protein remains the cornerstone of management, additional studies of underlying pathophysiology and biomarkers of disease will likely reveal new avenues for therapeutics.

Background: Atopic dermatitis (AD) is a chronic relapsing eczematous dermatitis typically affecting young patients in a percentage from 15 to 20%; although it typically affects young people and adults, recent papers highlighted the emerging of the disease in the elderly population., Methods: The aim of the study was to identify the clinical criteria and allergic sensitization that may be able to support physicians and dermatologists in making a correct diagnosis of AD in the elderly. The second aim of this study was to investigate the incidence, the main features, the gender prevalence, the immunological profile, and comorbidities characterizing patients older than 65 years affected by AD., Results: Based on clinical and serological patterns, different phenotypes of AD were identified: generalized AD (55%) characterized by eczematous lesions involving typical areas of the body or prurigo nodularis-like AD; chronic eczematous hand dermatitis (23%); face and neck involvement (9%); and nummular eczema (13%). Skin prick tests revealed a positivity for aeroallergens in 49.6% of patients, most of them being polysensitized (55%). Additionally, food skin prick tests were positive in 25% of patients. Most of the patients reported comorbidities, particularly IgE-mediated diseases, such as seasonal rhino-conjunctivitis, asthma, and chronic obstructive pulmonary disease. Gastrointestinal symptoms such as meteorism, dyspepsia, cramps/abdominal pain, and diarrhea/constipation, were observed in 35% of patients consequent to food allergy., Conclusion: In our study, we suggest clinical and serological criteria that may be able to guide in the diagnosis of AD in Caucasian elderly, and to design an appropriate treatment according to the current standard protocol., (© 2020 The International Society of Dermatology.)

Food allergy is rising at an alarming rate and is a major public health concern. Globally, food allergy affects over 500 million people, often starting in early childhood and increasingly reported in adults. Commercially, only one approved oral immunotherapy-based treatment is currently available and other allergen-based immunotherapeutic are being investigated in clinical studies. As an alternative approach, a substantial amount of research has been conducted on natural compounds and probiotics, focusing on the immune modes of action, and therapeutic uses of such sources to tackle various immune-related diseases. Food allergy is primarily mediated by IgE antibodies and the suppression of allergic symptoms seems to be mostly modulated through a reduction of allergen-specific IgE antibodies, upregulation of blocking IgG, and downregulation of effector cell activation (e.g., mast cells) or expression of T-helper 2 (Th-2) cytokines. A wide variety of investigations conducted in small animal models or cell-based systems have reported on the efficacy of natural bioactive compounds and probiotics as potential anti-allergic therapeutics. However, very few lead compounds, unlike anti-cancer and anti-microbial applications, have been selected for clinical trials in the treatment of food allergies. Natural products or probiotic-based approaches appear to reduce the symptoms and/or target specific pathways independent of the implicated food allergen. This broad range therapeutic approach essentially provides a major advantage as several different types of food allergens can be targeted with one approach and potentially associated with a lower cost of development. This review provides a brief overview of the immune mechanisms underlying food allergy and allergen-specific immunotherapy, followed by a comprehensive collection of current studies conducted to investigate the therapeutic applications of natural compounds and probiotics, including discussions of their mode of action and immunological aspects of their disease-modifying capabilities., (Copyright © 2020 Pratap, Taki, Johnston, Lopata and Kamath.)

Allergen-specific immunotherapy (AIT) is currently the only potential treatment for allergies including allergic rhinitis (AR) and food allergies (FA) that can modify the underlying course of the diseases. Although AIT has been performed for over a century, the precise and detailed mechanism for AIT is still unclear. Previous clinical trials have reported that successful AIT induces the reinstatement of tolerance against the specific allergen. In this review, we aim to provide an updated summary of the knowledge on the underlying mechanisms of IgE-mediated AR and FA as well as the immunological changes observed after AIT and discuss on how better understanding of these can lead to possible identification of biomarkers and novel strategies for AIT., (© 2020 The Author(s).)

This study investigated the properties of Scy p 9 in mud crab (Scylla paramamosain). The gene sequence of filamin C obtained from crabs, which was denoted as Scy p 9, contains a 2544 bp open reading frame and encodes 848 amino acid residues. Recombinant Scy p 9 (rScy p 9) is expressed in Escherichia coli, which exhibits tertiary structure changes, and the IgE binding activity of rScy p 9 is higher than that of native Scy p 9 (nScy p 9). Moreover, this study explored the possibility of the presence and cross-reactivity of filamin C in 8 shellfish. IgE-specific binding to nScy p 9 and rScy p 9 in patients allergic to shellfish revealed that rScy p 9 was more sensitive than nScy p 9. The gene sequence of filamin C fills in the blank in shellfish. This study contributes to the understanding of the properties of Scy p 9, and the results indicate that rScy p 9 can be used as a candidate for component-resolved diagnosis in shellfish.

Background: It is suspected that many canine cutaneous adverse food reactions (CAFR) are true immunological hypersensitivities; however, few specific dietary allergens have been identified., Objective: To compare serum immunoglobulin (Ig)E and IgG reactivity to specific food antigens in privately owned dogs with and without CAFR., Animals: Eighteen adult dogs with nonseasonal pruritus recruited from a hospital population., Methods and Materials: Dogs were fed an extensively hydrolysed poultry-based diet exclusively for 12 weeks. Serum was collected at the beginning of the trial. Canine atopic dermatitis extent and severity index and pruritus Visual Analog Scale scoring were performed at the beginning and end of the trial. Immunoblotting was performed to identify IgE and/or IgG binding to specific proteins in beef, egg, milk, chicken, pork, soy and wheat extracts., Results: A CAFR (defined as an unequivocal relapse of pruritus after dietary challenge) was diagnosed in 10 dogs, with 60% relapsing when fed chicken-based diets. Binding of subjects' IgG to almost all proteins in all extracts was seen regardless of reported dietary history. Few proteins were exclusively or predominantly bound by IgE in CAFR dogs. Exceptions included a 42 kDa band (chicken), a 52 kDa band (beef), a 46 kDa band (beef and milk) and a poorly defined high molecular weight protein or proteins (beef and milk)., Conclusion: This study demonstrated three protein bands and a poorly defined band predominantly recognized by sera from dogs with CAFR relative to non-CAFR dog sera. Almost all proteins were bound by IgG in all dogs, suggesting prior exposure to unreported foods., (© 2019 ESVD and ACVD.)

Purpose of Review: To review recent evidence on the capacity of vitamin D to prevent atopic disease, focussing on food allergy and asthma, and potential underlying mechanisms., Recent Findings: The incidence of allergic disease continues to increase worldwide. Vitamin D status is influenced by sun exposure and dietary intake. Vitamin D deficiency is linked to an increased incidence of allergic disease and asthma. These associations are generally strongest in early life. The capacity of vitamin D to enhance antimicrobial pathways, promote peripheral immunological tolerance and maintain mucosal barrier integrity may underlie these associations. Interventional studies have addressed the capacity of vitamin D supplementation in utero and early life to reduce the incidence of disease. Ancillary studies have provided insights into potential biological mechanisms linked to these effects., Summary: Observational studies show an inverse association between vitamin D levels and development of food allergy and asthma. Secondary analyses of two recent interventional studies suggest that achieving vitamin D sufficiency throughout pregnancy reduces the incidence of asthma/recurrent wheeze at 3 years. Longitudinal studies of vitamin D requirements in utero and postnatally, better understanding of factors that influence bioavailability of vitamin D and mechanistic insights into vitamin D effects on neonatal-specific immune pathways are awaited.

Background: Food allergy (FA) affects an increasing proportion of children for reasons that remain obscure. Novel disease biomarkers and curative treatment options are strongly needed., Objective: We sought to apply untargeted metabolomic profiling to identify pathogenic mechanisms and candidate disease biomarkers in patients with FA., Methods: Mass spectrometry-based untargeted metabolomic profiling was performed on serum samples of children with either FA alone, asthma alone, or both FA and asthma, as well as healthy pediatric control subjects., Results: In this pilot study patients with FA exhibited a disease-specific metabolomic signature compared with both control subjects and asthmatic patients. In particular, FA was uniquely associated with a marked decrease in sphingolipid levels, as well as levels of a number of other lipid metabolites, in the face of normal frequencies of circulating natural killer T cells. Specific comparison of patients with FA and asthmatic patients revealed differences in the microbiota-sensitive aromatic amino acid and secondary bile acid metabolism. Children with both FA and asthma exhibited a metabolomic profile that aligned with that of FA alone but not asthma. Among children with FA, the history of severe systemic reactions and the presence of multiple FAs were associated with changes in levels of tryptophan metabolites, eicosanoids, plasmalogens, and fatty acids., Conclusions: Children with FA have a disease-specific metabolomic profile that is informative of disease mechanisms and severity and that dominates in the presence of asthma. Lower levels of sphingolipids and ceramides and other metabolomic alterations observed in children with FA might reflect the interplay between an altered microbiota and immune cell subsets in the gut., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: LTX in children is associated with increased risk of food allergy, and the mechanisms underlying this are unknown. We wanted to study whether plasma cytokine profile differed in liver transplanted children, with and without food allergy, and whether it differed from untransplanted children with CLD., Methods: Plasma cytokines, total and specific IgE in nine patients with food allergy were compared with 13 patients without food allergy following LTX, and also with seven untransplanted patients with CLD., Results: No difference was found in the cytokine profile between liver transplanted patients with and without food allergy. Transplanted patients with food allergy having received a prescription of epinephrine had a significantly higher total IgE (2033 [234-2831] vs 10 [5-41] IU/L, P = .002) and MIP-1b (52 [37-96] vs 36 [32-39], P = .035) compared with transplanted patients without food allergy. Two patients with severe food allergy responded favorably to conversion from tacrolimus-based immunosuppression to MMF and corticosteroids with reduction in clinical symptoms, total IgE, specific IgE, IL-1ra, IL-4, RANTES, PDGF, MIP-1a, and TNFα. The transplantation group had higher levels of IL-1b, IL-5, IL-7, IL-13, GCSF, IFNγ, and MIP-1a compared with the CLD group., Conclusions: No overall difference was found in plasma cytokine profile between patients with and without food allergy. Patients with severe food allergy had significant elevation of MIP-1b. Discontinuation of tacrolimus reduced total and specific IgE and changed plasma cytokine profile. The plasma cytokine profile in liver transplanted children was different compared with children with CLD., (© 2020 The Authors. Pediatric Transplantation published by Wiley Periodicals, Inc.)

Hydrolyzed proteins are often prescribed for dogs with food hypersensitivity in food elimination programs. However, the potential of these diets to stimulate lymphocyte-mediated hypersensitivity is currently unknown. In this study, two commercially available hydrolyzed diets for dogs, D-1 (Aminopeptide Formula Dry, Royal Canin Japon, Tokyo, Japan), and D-2 (Canine z/d Ultra Dry, Hill's-Colgate (Japan) Ltd., Tokyo, Japan), were analyzed to identify residual proteins or peptides, as well as activated helper T-lymphocyte reactions in dogs with suspected food hypersensitivity. Proteins and peptides with molecular weights >1 kDa (majority 1.5-3.5 kDa) were detected in both diet extracts with sodium dodecyl sulfate polyacrylamide gel electrophoresis, and size exclusion chromatography. When peripheral blood mononuclear cells (PBMC's) from 316 dogs with suspected food allergies were cultured with hydrolyzed diet extracts, flow cytometry analysis revealed detectable levels of CD25 low helper T-lymphocytes stimulated by D-1 and D-2 in 91 of 316, (28.8%), and 75 of 316 (23.7%) samples, respectively. These data indicated that the extracts contained proteins or peptides large enough to activate the lymphocytes. The percentages of CD25 low helper T-lymphocytes stimulated by D-1 and D-2 extracts increased to 38.7% and 29.6%, respectively, in 186 of the original 316 samples (186/316, 58.9%), also reactive to poultry-related antigens. Thus, both poultry-related antigens, and D-1 and D-2 diet extracts may activate helper T-lymphocytes. These results demonstrate that hydrolyzed diets may contain proteins that stimulate helper T-lymphocytes, and may not be effective for treating all dogs with food hypersensitivity.

Eosinophils have emerged as multifaceted cells that contribute to tissue homeostasis. However, the impact of the microbiota on their frequency and function at mucosal sites remains unclear. Here, we investigated the role of the microbiota in the regulation of enteric eosinophils. We found that small intestinal (SI) eosinophilia was significantly greater in germ-free (GF) mice compared to specific pathogen free (SPF) controls. This was associated with changes in the production of enteric signals that regulate eosinophil attraction and survival, and was fully reversed by complex colonization. Additionally, SI eosinophils of GF mice exhibited more cytoplasmic protrusions and less granule content than SPF controls. Lastly, we generated a novel strain of eosinophil-deficient GF mice. These mice displayed intestinal fibrosis and were less prone to allergic sensitization as compared to GF controls. Overall, our study demonstrates that commensal microbes regulate intestinal eosinophil frequency and function, which impacts tissue repair and allergic sensitization to food antigens. These data support a critical interplay between the commensal microbiota and intestinal eosinophils in shaping homeostatic, innate, and adaptive immune processes in health and disease., (Copyright © 2020 Jiménez-Saiz, Anipindi, Galipeau, Ellenbogen, Chaudhary, Koenig, Gordon, Walker, Mandur, Abed, Humbles, Chu, Erjefält, Ask, Verdú and Jordana.)

Food protein allergies are a major global concern. Hydrolysis of food proteins reduces their allergenicity, but another novel approach is the covalent attachment of polysaccharides to proteins via the Maillard reaction (i.e., glycation), which blocks some IgE binding epitopes on the protein allergen. We wanted to examine whether enzymatic hydrolysis, combined with glycation, could further reduce IgE binding for people with a cow milk protein allergy. Whey protein isolate (WPI) was hydrolyzed by immobilized trypsin and chymotrypsin to degree of hydrolysis (DH) values of 17 to 27%. Immobilized enzymes were used to avoid heat-treating the hydrolysate (to inactivate the enzymes, because heating could also affect the IgE binding ability of the protein). The resultant whey protein isolate hydrolysates (WPIH) were then glycated with 10-kDa dextran (DX) in aqueous solutions held at 62°C for 24 h. We analyzed the molar mass (M W ) of WPIH samples and their corresponding glycates (WPIH-DX) using size-exclusion chromatography with multi-angle laser light scattering. We obtained blood sera from 8 patients who had been diagnosed with a cow milk protein allergy, and we used a composite serum for IgE binding analysis. The average M W values of samples WPIH-1 to WPIH-3 decreased from 11.15, 9.46, and 7.57 kDa with increasing DH values of 18.7, 22.5, and 27.1%. Glycation significantly reduced the high bitterness of the WPIH samples, as assessed by a trained sensory panel. The WPIH-DX glycates had significantly reduced WPI-specific IgE binding capacity compared to WPI or unglycated WPIH; we found an almost 99% reduction in IgE binding for the WPIH-DX glycate made from WPIH with a DH value of 27.1%. Hydrolysis of WPI followed by glycation with DX via the Maillard reaction significantly decreased the allergenicity of whey proteins., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Significant efforts are necessary to introduce new dietary protein sources to feed a growing world population while maintaining food supply chain sustainability. Such a sustainable protein transition includes the use of highly modified proteins from side streams or the introduction of new protein sources that may lead to increased clinically relevant allergic sensitization. With food allergy being a major health problem of increasing concern, understanding the potential allergenicity of new or modified proteins is crucial to ensure public health protection. The best predictive risk assessment methods currently relied on are in vivo models, making the choice of endpoint parameters a key element in evaluating the sensitizing capacity of novel proteins. Here, we provide a comprehensive overview of the most frequently used in vivo and ex vivo endpoints in murine food allergy models, addressing their strengths and limitations for assessing sensitization risks. For optimal laboratory-to-laboratory reproducibility and reliable use of predictive tests for protein risk assessment, it is important that researchers maintain and apply the same relevant parameters and procedures. Thus, there is an urgent need for a consensus on key food allergy parameters to be applied in future food allergy research in synergy between both knowledge institutes and clinicians., (© 2019 The Authors. Allergy Published by John Wiley & Sons Ltd.)

Background: Diagnosing coeliac disease (CD) in patients on a gluten-free diet (GFD) is difficult. Ingesting gluten elevates circulating interleukin (IL)-2, IL-8 and IL-10 in CD patients on a GFD., Objective: We tested whether cytokine release after gluten ingestion differentiates patients with CD from those with self-reported gluten sensitivity (SR-GS)., Methods: Australian patients with CD ( n  = 26) and SR-GS ( n  = 18) on a GFD consumed bread (estimated gluten 6 g). Serum at baseline and at 3 and 4 h was tested for IL-2, IL-8 and IL-10. Separately, Norwegian SR-GS patients ( n  = 49) had plasma cytokine assessment at baseline and at 2, 4 and 6 h after food bars containing gluten (5.7 g), fructan or placebo in a previous double-blind crossover study., Results: Gluten significantly elevated serum IL-2, IL-8 and IL-10 at 3 and 4 h in patients with CD but not SR-GS. The highest median fold-change from baseline at 4 h was for IL-2 (8.06, IQR: 1.52-24.0; P  < 0.0001, Wilcoxon test). The two SR-GS cohorts included only one (1.5%) confirmed IL-2 responder, and cytokine responses to fructan and placebo were no different to gluten. Overall, cytokine release after gluten was present in 22 (85%) CD participants, but 2 of the 4 non-responders remained clinically well after 1 y on an unrestricted diet. Hence, cytokine release occurred in 22 (92%) of 24 'verified' CD participants., Conclusions: Gluten challenge with high-sensitivity cytokine assessment differentiates CD from SR-GS in patients on a GFD and identifies patients likely to tolerate gluten reintroduction. Systemic cytokine release indicating early immune activation by gluten in CD individuals cannot be detected in SR-GS individuals.