Food Antigens Research Articles

A novel in vitro model of the small intestinal epithelium in co-culture with 'gut-like' dendritic cells.

Cross-talk between dendritic cells (DCs) and the intestinal epithelium is important in the decision to mount a protective immune response to a pathogen or to regulate potentially damaging responses to food antigens and the microbiota. Failures in this decision-making process contribute to the development of intestinal inflammation, making the molecular signals that pass between DCs and intestinal epithelial cells potential therapeutic targets. Until now, in vitro models with sufficient complexity to understand these interactions have been lacking. Here, we outline the development of a co-culture model of in vitro differentiated 'gut-like' DCs with small intestinal organoids (enteroids). Sequential exposure of murine bone marrow progenitors to Flt3L, granulocyte macrophage colony-stimulating factor (GM-CSF) and all-trans-retinoic acid (RA) resulted in the generation of a distinct population of conventional DCs expressing CD11b+SIRPα+CD103+/- (cDC2) exhibiting retinaldehyde dehydrogenase (RALDH) activity. These 'gut-like' DCs extended transepithelial dendrites across the intact epithelium of enteroids. 'Gut-like' DC in co-culture with enteroids can be utilized to define how epithelial cells and cDCs communicate in the intestine under a variety of different physiological conditions, including exposure to different nutrients, natural products, components of the microbiota, or pathogens. Surprisingly, we found that co-culture with enteroids resulted in a loss of RALDH activity in 'gut-like' DCs. Continued provision of GM-CSF and RA during co-culture was required to oppose putative negative signals from the enteroid epithelium. Our data contribute to a growing understanding of how intestinal cDCs assess environmental conditions to ensure appropriate activation of the immune response.

A systematic review of the knowledge and training of food service workers on food allergies

<abstract><sec> <title>Background</title> <p>Food allergies are adverse reactions to a specific food antigen which is mediated by immunological mechanisms and are fast rising to become a significant public health concern. Around 1% of the world's adult population suffers from food allergies. The prevalence of food allergies which can be life-threatening is commonly estimated to affect 3–5% of the adult population in North America.</p> </sec><sec> <title>Objectives</title> <p>The purpose of this study is to review published food allergy knowledge and training amongst food service workers and identify the policies in place concerning food allergies globally.</p> </sec><sec> <title>Methodology</title> <p>Documented food service workers' knowledge and training about food allergies published between September 2006 and February 2021 were comprehensively reviewed. A widespread literature search was carried out using subject headings, search terms, and keywords. Results were examined in groups to explore patterns through research.</p> </sec><sec> <title>Results</title> <p>A total of 18 relevant studies that analyzed the food allergies knowledge and training of food service workers were reviewed. Eight studies (44%) were performed in the USA, followed by two studies (11%) in the UK, and one study each (5%) for New Zealand, Turkey, Malaysia, France, Western Romania, Germany, Brazil, and Canada. In the studies, respondents were asked a series of questions to assess their level of knowledge and the types of training relating to food allergies they received.</p> </sec><sec> <title>Conclusions</title> <p>This study identified the gaps in policy, as well as knowledge and training among food service workers, to manage food allergies safely, thus emphasizing the importance and need for food allergy training.</p> </sec></abstract>

Immune background state among the residents of the north, depending on nutrition type

ABSTRACT The questionnaire survey and the study of 1334 people living in the north of the European part of the Russian Federation, of which 970 are women and 364 are men, was conducted. 707 residents of the Arkhangelsk region and 627 residents of the Nenets Autonomous Okrug. The results of the questionnaire were analyzed depending on the appetite state (decreased -102 respondents, increased - 276, normal appetite – 1096, as well as dietary compliance – 124 and adherence to vegetarianism – 139). The most pronounced combined defects of immune protection (deficiency of phagocytic protection, deficiency of the content of natural killers and T-helpers) occur in people who have been eating mainly cereals and bread for a long time. Increased appetite in people over 55 years of age is associated with the frequency of chronic diseases of the gastrointestinal tract (35.7%) and increased tolerance to food antigens (52.3%).

Impacts of gut microbiota on human health and diseases

Numerous microorganisms that are important to the health of their host are found in abundance in the human gut. They can, however, also be potentially dangerous because of the alteration in their composition that occurs when the gut ecosystem experiences aberrant changes as a result of the use of antibiotics, sickness, stress, age, poor dietary practices, and lifestyle choices. Dysbiosis of the gut micro biota on humans has harmful health effects that can result in a number of chronic disorders. The potential of probiotics to treat certain disorders has led to much research into them. They are typically thought of as helpful microbes; additionally, when their products are supplied to humans in sufficient doses, they act as health adjuvants. Probiotics can prevent the beginning of disease through a number of processes, including altering gut bacteria, producing short-chain fatty acids, reducing intestinal pH, producing antimicrobial compounds, and suppressing epithelial binding growth. Additionally, they help to inhibit the invasion of pathogenic organisms, regulate the transfer of food antigens, enhance intestinal barrier performance, and alter host immunological responses. Probiotic tests have revealed encouraging outcomes in the prevention of diseases such as diarrhea, irritable bowel syndrome, colon cancer, and Crohn’s disease. Numerous epidemiological and experimental investigations, particularly those focusing on the gut microbiota, have contributed to shed light on the role of probiotics as preventative agents. This review provides a potential target for the illness prevention and treatment by summarizing and discussing the roles and potential mechanisms of gut bacteria in human health and disorders.

High Discovery Rate of Duodenal and Gastric Eosinophilia in Patients With Unexplained Moderate–Severe Abdominal Symptoms: A Prospective US Multisite Study

High Discovery Rate of Duodenal and Gastric Eosinophilia in Patients With Unexplained Moderate–Severe Abdominal Symptoms: A Prospective US Multisite Study

Gut-brain axis: Review on the association between Parkinson's disease and plant lectins.

Gastrointestinal (GI) involvement in the pathogenesis of Parkinson's Disease (PD) has been widely recognized and supported in recent literature. Prospective and retrospective studies found non-motor symptoms within the GI, specifically constipation, precede cardinal signs and cognitive decline by almost 20 years. In 2002, Braak et al. were the first to propose that PD is a six-stage propagating neuropathological process originating from the GI tract (GIT). Aggregated α-synuclein (α-syn) protein from the GIT is pathognomonic for the development of PD. This article reviews the current literature from the past 10 years as well as original research found in PubMed on the combined effects of enteric glial cells and lectins on the development of Parkinson's Disease. Studies have found that these aggregated and phosphorylated proteins gain access to the brain via retrograde transport through fast and slow fibers of intestinal neurons. Plant lectins, commonly found within plant-based diets, have been found to induce Leaky Gut Syndrome and can activate enteric glial cells, causing the release of pro-inflammatory cytokines. Oxidative stress on the enteric neurons, caused by a chronic neuro-inflammatory state, can cause a-syn aggregation and lead to Lewy Body formation, a hallmark finding in PD. Although the current literature provides a connection between the consumption of plant lectins and the pathophysiology of PD, further research is required to evaluate confounding variables such as food antigen mimicry and other harmful substances found in our diets.

Perinatal exposure to foodborne inorganic nanoparticles: A role in the susceptibility to food allergy?

Food allergy (FA) is an inappropriate immune response against dietary antigens. Various environmental factors during perinatal life may alter the establishment of intestinal homeostasis, thereby predisposing individuals to the development of such immune-related diseases. Among these factors, recent studies have emphasized the chronic dietary exposure of the mother to foodborne inorganic nanoparticles (NP) such as nano-sized silicon dioxide (SiO2), titanium dioxide (TiO2) or silver (Ag). Indeed, there is growing evidence that these inorganic agents, used as food additives in various products, as processing aids during food manufacturing or in food contact materials, can cross the placental barrier and reach the developing fetus. Excretion in milk is also suggested, hence continuing to expose the neonate during a critical window of susceptibility. Due to their immunotoxical and biocidal properties, such exposure may disrupt the host-intestinal microbiota's beneficial exchanges and may interfere with intestinal barrier and gut-associated immune system development in fetuses then the neonates. The resulting dysregulated intestinal homeostasis in the infant may significantly impede the induction of oral tolerance, a crucial process of immune unresponsiveness to food antigens. The current review focuses on the possible impacts of perinatal exposure to foodborne NP during pregnancy and early life on the susceptibility to developing FA.

Ion channel regulation of gut immunity.

Mounting evidence indicates that gastrointestinal (GI) homeostasis hinges on communications among many cellular networks including the intestinal epithelium, the immune system, and both intrinsic and extrinsic nerves innervating the gut. The GI tract, especially the colon, is the home base for gut microbiome which dynamically regulates immune function. The gut's immune system also provides an effective defense against harmful pathogens entering the GI tract while maintaining immune homeostasis to avoid exaggerated immune reaction to innocuous food and commensal antigens which are important causes of inflammatory disorders such as coeliac disease and inflammatory bowel diseases (IBD). Various ion channels have been detected in multiple cell types throughout the GI tract. By regulating membrane properties and intracellular biochemical signaling, ion channels play a critical role in synchronized signaling among diverse cellular components in the gut that orchestrates the GI immune response. This work focuses on the role of ion channels in immune cells, non-immune resident cells, and neuroimmune interactions in the gut at the steady state and pathological conditions. Understanding the cellular and molecular basis of ion channel signaling in these immune-related pathways and initial testing of pharmacological intervention will facilitate the development of ion channel-based therapeutic approaches for the treatment of intestinal inflammation.

Allergenic food protein consumption is associated with systemic IgG antibody responses in non-allergic individuals

Although food-directed immunoglobulin E (IgE) has been studied in the context of allergies, the prevalence and magnitude of IgG responses against dietary antigens are incompletely characterized in the general population. Here, we measured IgG binding against food and environmental antigens obtained from allergen databases and the immune epitope database (IEDB), represented in a phage displayed library of 58,233 peptides. By profiling blood samples of a large cohort representing the average adult Israeli population (n= 1,003), we showed that many food antigens elicited systemic IgG in up to 50% of individuals. Dietary intake of specific food protein correlated with antibody binding, suggesting that diet can shape the IgG epitope repertoire. Our work documents abundant systemic IgG responses against food antigens and provides a reference map of the exact immunogenic epitopes on a population scale, laying the foundation to unravel the role of food- and environmental antigen-directed antibody binding in disease contexts.

Clinical-immunological phenotypes of the autistic spectrum disorders

Autistic spectrum disorders (ASD) affect about one in every 59 children. It is noteworthy that patients with ASD are more likely to have other comorbidities than the general population. Undoubtedly, they may aggravate clinical course of the underlying disease or affect the diagnostics. The aim of this work was to identify clinical and immunological phenotypes of the ASD clinical course. Patients and methods. The study included children classified in 2 groups: pediatric patients with ASD (n = 100), and clinically healthy children (n = 30). Based on the presence of comorbidities, the children were divided into 3 types of clinical patterns: convulsive, infectious, dermato-respiratory and gastrointestinal phenotypes. Cytokine concentrations in blood serum were determined by ELISA using Bender Medsystems (Austria) for IL-17А and Vector-Best (Russia) for IL-4, IL-6, IL-10, IFNγ. The concentration of spIgG to 111 nutritional antigens (IgG) was determined by a modified ELISA method using the Immunohealth™ technique. Assessment of cognitive and psychophysiological indices in children was carried out using the ATEC questionnaire. As a result of the study, clinical and immunological phenotypes were identified among the ASD patients, being associated with certain types of food tolerance, cytokine profile, clinical severity of psycho-physiological disorders and concomitant comorbid diseases. In all four phenotypes, were have revealed an increased synthesis of specific antibodies associated with humoral immunity for the studied food antigens, increased concentration of total spIgG to food antigens, concentration of spIgG to legumes and casein, and C-reactive protein levels.Moreover, in convulsive phenotype (concomitant epilepsy and convulsions), the maximal concentrations of spIgG are shown for Solanaceae products, the concentration of IL-10 is increased, IL-4 amounts are reduced, and the content of serum iron and ferritin is also lowered. In the infectious phenotype (frequently ill children) the spIg’s to grain and fermented products are detected, IL-10 and IFNγ concentrations are increased and IL-4 contents is reduced, along with increased absolute and relative number of lymphocytes and fibrinogen. In the dermato-respiratory phenotype (skin rashes) – to dairy products, the concentrations of IL-4 and IL-17A are increased. In the gastrointestinal phenotype, the highest number of elevated IgG responses to the largest range of food antigens was found in presence of changing cytokine profile , i.e., an increase in IFNγ in IFNγ/IL-4 and IFNγ/IL-10 ratios. Thus, the identified phenotypes of the ASD course are associated with the influence of food antigens and reflect a special variant of the immunological inflammatory pathogenesis, which makes it possible to personalize elimination diets, propose measures for correction and individual prevention, and, probably, to predict clinical course of the disease.

Genetic regulation of serum IgA levels and susceptibility to common immune, infectious, kidney, and cardio-metabolic traits

Immunoglobulin A (IgA) mediates mucosal responses to food antigens and the intestinal microbiome and is involved in susceptibility to mucosal pathogens, celiac disease, inflammatory bowel disease, and IgA nephropathy. We performed a genome-wide association study of serum IgA levels in 41,263 individuals of diverse ancestries and identified 20 genome-wide significant loci, including 9 known and 11 novel loci. Co-localization analyses with expression QTLs prioritized candidate genes for 14 of 20 significant loci. Most loci encoded genes that produced immune defects and IgA abnormalities when genetically manipulated in mice. We also observed positive genetic correlations of serum IgA levels with IgA nephropathy, type 2 diabetes, and body mass index, and negative correlations with celiac disease, inflammatory bowel disease, and several infections. Mendelian randomization supported elevated serum IgA as a causal factor in IgA nephropathy. African ancestry was consistently associated with higher serum IgA levels and greater frequency of IgA-increasing alleles compared to other ancestries. Our findings provide novel insights into the genetic regulation of IgA levels and its potential role in human disease.

Phenotyping of immediate-type food allergies based on 10 years of research: A latent class analysis.

Food allergy is a disease with a diverse and variable natural history, and some patients may react to two or more food antigens. This study aimed to classify and characterize the long-term prognosis of infantile-onset, immediate-type food allergies, focusing on three major antigens in Japan: egg, milk, and wheat. All children who visited our hospital with food allergies, including suspected cases, were prospectively registered in our medical database. Among the children in this database, subjects registered by the age of 1year with immediate-type symptoms or sensitization to the above three antigens were included. The course of the subjects up to the age of 6 years was analyzed. Cox regression analysis and repeated-measures latent class analysis (LCA) were performed to reveal risk factors and tolerance patterns for food allergies. We included 915 patients with immediate-type food allergy symptoms and 276 sensitized asymptomatic patients in this study. The number of patients with immediate-type symptoms to egg, milk, and wheat was 609, 443, and 235, respectively. The number of patients with multiple food allergies was 302. The proportion of patients with tolerance to egg, milk, and wheat at 6 years of age was 74%, 69%, and 75%, respectively. LCA revealed 7 classes of prognosis for food allergies. The largest class was transient egg allergy alone (19.6%), and there were severe cases of multiple food allergies (6.5%). This study demonstrated the prognosis of food allergy classes in Japan, including multiple food allergies, with 7 classes with its own characteristics.

The Role of the Gut Microbiome in Cow's Milk Allergy: A Clinical Approach.

Cow's milk allergy (CMA) is the most prevalent food allergy (FA) in infancy and early childhood and can be present with various clinical phenotypes. The significant increase in FA rates recorded in recent decades has been associated with environmental and lifestyle changes that limit microbial exposure in early life and induce changes in gut microbiome composition. Gut microbiome is a diverse community of microbes that colonize the gastrointestinal tract (GIT) and perform beneficial functions for the host. This complex ecosystem interacts with the immune system and has a pivotal role in the development of oral tolerance to food antigens. Emerging evidence indicates that alterations of the gut microbiome (dysbiosis) in early life cause immune dysregulation and render the host susceptible to immune-mediated diseases later in life. Therefore, the colonization of the gut by "healthy" microbes that occurs in the first years of life determines the lifelong health of the host. Here, we present current data on the possible role of the gut microbiome in the development of CMA. Furthermore, we discuss how gut microbiome modification might be a potential strategy for CMA prevention and treatment.

Manipulating the microbiome to enhance oral tolerance in food allergy

Loss of oral tolerance (OT) to food antigens results in food allergies. One component of achieving OT is the symbiotic microorganisms living in the gut (microbiota). The composition of the microbiota can drive either pro-tolerogenic or pro-inflammatory responses against dietary antigens though interactions with the local immune cells within the gut. Products from bacterial fermentation, such as butyrate, are one of the main communication molecules involved in this interaction, however, this is released by a subset of bacterial species. Thus, strategies to specifically expand these bacteria with protolerogenic properties have been explored to complement oral immunotherapy in food allergy. These approaches either provide digestible biomolecules to induce beneficial bacteria species (prebiotics) or the direct administration of live bacteria species (probiotics). While this combined therapy has shown positive outcomes in clinical trials for cow’s milk allergy, more research is needed to determine if this therapy can be extended to other food allergens.

Diagnostic management of patients reporting symptoms after wheat ingestion.

Many patients report symptoms after wheat ingestion experiencing a wide spectrum of clinical manifestations. Three possible diagnoses have been recognized: celiac disease (CD), wheat allergy (WA), and non-celiac (gluten) wheat sensitivity (NCGS/NCWS). CD is a chronic immune-mediated disease of the small bowel caused by exposure to dietary gluten in genetically predisposed individuals, with a prevalence of approximately 1%. It is characterized by mucosal inflammation and atrophy following exposure to gluten and improvement after gluten withdrawal. Food allergies are immunological responses to a food antigen. WA is the expression of an immunologically mediated process that can be immunoglobulin E (IgE) or non-IgE mediated; its many symptoms include urticaria/angioedema, asthma, rhinitis, and anaphylaxis. NCGS/NCWS is characterized by gastrointestinal and/or extra-intestinal symptoms after ingestion of gluten-containing food in subjects not affected by CD or WA. The aim of this review is to help physicians and nutritionists diagnose the cause of symptoms reported after wheat ingestion, thus avoiding patient frustration, inappropriate testing, and incorrect or missed diagnoses. An algorithm for the diagnostic approach in these patients is provided, to help to diagnose CD, WA, NCGS/NCWS or to identify possible functional disorders as the wheat-sensitive irritable bowel syndrome. A personalized approach, regular follow-up, and the help of a skilled healthcare professional are mandatory for patients with symptoms following wheat ingestion is provided. A gluten-free-diet is often recommended for patients with self-reported gluten/wheat-dependent symptoms; for patients with symptoms similar to those of functional diseases while there is evidence that a low-FODMAP diet could be the first option.

S572 A Pilot Study for Precision Nutrition in Irritable Bowel Syndrome: In-Vitro Stimulation of Pro-and Anti-inflammatory Cytokine Release

Introduction: Inflammation plays a role in the pathogenesis of irritable bowel syndrome (IBS). Foods can trigger and exacerbate IBS flare-ups and symptoms. Diet-induced inflammation is characterized by the release of cytokines as a common feature. The lack of evidence regarding which diet is ideal for IBS underlined the need for personalized and more precise dietary treatment options. The objective of this study was to determine in-vitro the degree of blood inflammatory cytokines release in response to food antigens exposure in subjects with IBS. Methods: Blood samples were collected at Oxford Biomedical Technologies, Inc. from 12 subjects diagnosed with IBS. Whole blood was diluted with buffered physiologic saline, and then an aliquot was pipetted into eight reaction wells, each containing a single food extract. Following a predetermined incubation period at 37°C, all specimens were stored at -20°C until cytokine analysis were performed. Cytokines [interleukin-8 (IL) and IL-10)] reactivity to food antigens challenge was evaluated using Bio-Plex 200 System (Bio-Rad, CA). The IBS-Severity Scoring System (IBS-SSS) was used to measure the severity and intensity of symptoms. The questionnaire scores range from 0 to 500, with cutoffs rated as mild (75-175), moderate (175-300), and severe ( >300). The study received approval from an independent Institutional Review Board (IRB), and all statistical analyses were performed using SPSS version 27.0 (IBM Corp., NY). Results: Mean age was 52.2±17.5 years, 10 (83%) were female and had a BMI of 26.2±5.7 kg/m2. According to IBS-SSS scores, 8 (67%) of the subjects had moderate symptoms, whereas 4 (33%) had severe symptoms. We found statistically significant differences in IL-8 and IL-10 concentrations (pg/mL) release pre- vs. post-antigen exposure to broccoli [(2.17±0.75, P=0.016)]; corn [(1.25±0.44, P=0.018) and (-0.21±0.09, P=0.041)]; milk [(1.40±0.48, P=0.017); egg [(1.17±0.48, P=0.034)]; navy bean [(0.83±0.30, P=0.019) and (-0.14±0.01, P=.004)]; orange [(2.19±1.04, P=0.063)]; tomato [(2.77±1.15, P=0.038) and (-0.26±0.13; P=0.073)]; and wheat [(0.90±0.36, P=0.033) and (-0.27±0.08, P=0.011)] respectively. Conclusion: The findings from this study generate much-needed data to aid the understanding of non-physiological inflammatory responses to foods which can optimize targeted dietary therapy for IBS. Further work is needed to develop a diagnostic assay that could be used to create a precise and personalized diet for clinical practice.

The Gut and Kidney Crosstalk in Immunoglobulin A Nephropathy.

Immunoglobulin A nephropathy(IgAN) is the most common primary glomerulonephritis worldwide. The working model for the pathogenesis of IgAN involves a multistep process starting from the production of galactose-deficient and polymeric immunoglobulin A-1 (gd-IgA1) that enters systemic circulation from gut-associated lymphoid tissue (GALT). Galactose-deficient IgA are targeted by endogenous IgG, leading to the formation of circulating immune complexes that deposit in the mesangium and resulting in glomerular inflammation. Disease onset and relapses are often associated with gut infections, supporting the hypothesis that the gut plays an important pathogenic role. In the presence of microbial pathogens or food antigens, activated dendritic cells in the gut mucosa induce T cell dependent and independent B cell differentiation into IgA secreting plasma cells. In IgAN patients, this promotes the systemic release of mucosal gd-IgA1. Not all bacterial strains have the same capacity to elicit IgA production, and little is known about the antigen specificity of the pathogenic gd-IgA1. However, efficacy of treatments targeting gut inflammation support a pathogenic link between the bowel immune system and IgAN. Herein, we review the evidence supporting the role of gut inflammation in IgAN pathogenesis.

Allergy-Test-Based Elimination Diets for the Treatment of Eosinophilic Esophagitis: A Systematic Review of Their Efficacy.

Eosinophilic esophagitis (EoE) is an immune-mediated esophageal disorder, linked with sensitization to food and airborne allergens. Dietary manipulations are proposed for the management of EoE inflammation and are often successful, confirming the etiological role of food allergens. Three different dietary approaches are widely used: the elemental, the empirical, and the allergy-test-driven approach. We performed a systematic review to assess the evidence on the association of allergens, detected by allergy tests, with clinically confirmed triggers of EoE. We systematically searched PubMed, Scopus, Embase, and the Cochrane Library, through 1 June 2021. We sought studies examining the correlation of skin-prick tests (SPT), atopy patch tests (APT), specific IgE, and serum-specific IgG4, with confirmed triggers of EoE. Data on the use of prick–prick tests were also extracted. Evidence was independently screened by two authors against predefined eligibility criteria. Risk of bias was assessed with the ROBINS-I tool. Of 52 potentially eligible studies, 16 studies fulfilling quality criteria were included. These studies used one to three different allergy tests detecting food sensitization. The positive predictive value was generally low to moderate but higher when a combination of tests was used than single-test evaluations. None of the selected studies used serum-specific IgG4. Although an extreme methodological variability was noticed in the studies, allergy-based elimination diets were estimated to be efficient in 66.7% of the cases. The efficacy of targeted elimination diets, guided by SPT, sIgE, and/or APT allergy tests, does not appear superior to empirical ones. In the future, tests using esophageal prick testing or ex vivo food antigen stimulation may prove more efficient to guide elimination diets.

Reaction of SARS-CoV-2 antibodies with other pathogens, vaccines, and food antigens.

It has been shown that SARS-CoV-2 shares homology and cross-reacts with vaccines, other viruses, common bacteria and many human tissues. We were inspired by these findings, firstly, to investigate the reaction of SARS-CoV-2 monoclonal antibody with different pathogens and vaccines, particularly DTaP. Additionally, since our earlier studies have shown immune reactivity by antibodies made against pathogens and autoantigens towards different food antigens, we also studied cross-reaction between SARS-CoV-2 and common foods. For this, we reacted monoclonal and polyclonal antibodies against SARS-CoV-2 spike protein and nucleoprotein with 15 different bacterial and viral antigens and 2 different vaccines, BCG and DTaP, as well as with 180 different food peptides and proteins. The strongest reaction by SARS-CoV-2 antibodies were with DTaP vaccine antigen, E. faecalis, roasted almond, broccoli, soy, cashew, α+β casein and milk, pork, rice endochitinase, pineapple bromelain, and lentil lectin. Because the immune system tends to form immune responses towards the original version of an antigen that it has encountered, this cross-reactivity may have its advantages with regards to immunity against SARS-CoV-2, where the SARS-CoV-2 virus may elicit a “remembered” immune response because of its structural similarity to a pathogen or food antigen to which the immune system was previously exposed. Our findings indicate that cross-reactivity elicited by DTaP vaccines in combination with common herpesviruses, bacteria that are part of our normal flora such as E. faecalis, and foods that we consume on a daily basis should be investigated for possible cross-protection against COVID-19. Additional experiments would be needed to clarify whether or not this cross-protection is due to cross-reactive antibodies or long-term memory T and B cells in the blood.

Food antigen consumption and disease activity affect food-specific IgG4 levels in patients with eosinophilic esophagitis (EoE).

High levels of serum food-specific IgG4 (sIgG4) have been reported in patients with EoE. The objective of this study was to examine whether serum sIgG4 levels to foods and aeroallergens are higher in EoE patients than allergic controls and to investigate the association between sIgG4 and EoE clinical characteristics. This was a case-control study nested in a prospective EoE Cohort. EoE cases were defined per consensus guidelines, and controls were individuals with symptoms who were confirmed to be EoE-negative on upper endoscopy. Demographic and clinical information was prospectively collected. Serum IgE and sIgG4 were measured to foods and aeroallergens by ImmunoCAP. Mean levels of sIgG4 were compared between cases and controls, and logistic regression models were used to examine predictors of elevated milk sIgG4 levels. The analysis included 123 individuals (EoE n=93, control n=30) with a similar distribution of allergic disease between EoE patients and controls (86% vs. 93%; p=.30). EoE patients had significantly higher sIgG4 levels to all allergens evaluated, with the exception of birch (p=.24). Milk sIgG4 levels were independently associated with milk consumption (OR 4.95; p=.01) and the presence of sIgE to milk (OR 4.23; p=.008). Serum sIgG4 levels to food and aeroallergen proteins were higher in patients with EoE than non-EoE controls, and higher levels of milk sIgG4 were independently associated with milk consumption and the presence of sIgE to milk proteins. Whether sIgG4 plays a pathogenic role in EoE or could be used as an EoE biomarker remains unknown and warrants further study.