ABSTRACT
Eosinophils not only function as inflammatory effectors in allergic diseases, but also contribute to tissue homeostasis in steady state. Emerging data are revealing tissue eosinophils to be adaptive cells, imprinted by their local tissue microenvironment and exhibiting distinct functional phenotypes that may contribute to their homeostatic vs. inflammatory capacities. However, signaling pathways that regulate eosinophil tissue adaptations remain elusive. Notch signaling is an evolutionarily conserved pathway that mediates differential cell fate programming of both pre- and postmitotic immune cells. This study investigated a role for notch receptor 2 signaling in regulating eosinophil functions and tissue phenotype in both humans and mice. Notch 2 receptors were constitutively expressed and active in human blood eosinophils. Pharmacologic neutralization of notch 2 in ex vivo stimulated human eosinophils altered their activated transcriptome and prevented their cytokine-mediated survival. Genetic ablation of eosinophil-expressed notch 2 in mice diminished steady-state intestine-specific eosinophil adaptations and impaired their tissue retention in a food allergic response. In contrast, notch 2 had no effect on eosinophil phenotype or tissue inflammation within the context of allergic airways inflammation, suggesting that notch 2-dependent regulation of eosinophil phenotype and function is specific to the gut. These data reveal notch 2 signaling as a cell-intrinsic mechanism that contributes to eosinophil survival, function, and intestine-specific adaptations. The notch 2 pathway may represent a viable strategy to reprogram eosinophil functional phenotypes in gastrointestinal eosinophil-associated diseases.
Subject(s)
Allergens , Eosinophils , Receptor, Notch2 , Signal Transduction , Animals , Eosinophils/immunology , Eosinophils/metabolism , Receptor, Notch2/metabolism , Humans , Allergens/immunology , Mice , Intestines/immunology , Intestines/pathology , Mice, Inbred C57BL , Adaptation, Physiological/immunology , Mice, Knockout , Food Hypersensitivity/immunology , Food Hypersensitivity/pathologyABSTRACT
Atopic dermatitis (AD), characterized by rashes, itching, and pruritus, is a chronic inflammatory condition of the skin with a marked infiltration of inflammatory cells into the lesion. It usually commences in early childhood and coexists with other atopic diseases such as allergic rhinitis, bronchial asthma, allergic conjunctivitis, etc. With a prevalence rate of 1-20% in adults and children worldwide, AD is gradually becoming a major health concern. Immunological aspects have been frequently focused on in the pathogenesis of AD, including the role of the epidermal barrier and the consequent abnormal cytokine expressions. Disrupted epidermal barriers, as well as allergic triggers (food allergy), contact allergens, irritants, microbes, aggravating factors, and ultraviolet light directly initiate the inflammatory response by inducing epidermal keratinocytes, resulting in the abnormal release of various pro-inflammatory mediators, inflammatory cytokines, and chemokines from keratinocytes. In addition, abnormal proteinases, gene mutations, or single nucleotide polymorphisms (SNP) affecting the function of the epidermal barrier can also contribute towards disease pathophysiology. Apart from this, imbalances in cholinergic or adrenergic responses in the epidermis or the role played by immune cells in the epidermis such as Langerhans cells or antigen-presenting cells can also aggravate pathophysiology. The dearth of specific biomarkers for proper diagnosis and the lack of a permanent cure for AD necessitate investigation in this area. In this context, the widespread role played by keratinocytes in the pathogenesis of AD will be reviewed in this article to facilitate the opening up of new avenues of treatment for AD.
Subject(s)
Dermatitis, Atopic , Food Hypersensitivity , Adult , Child , Child, Preschool , Cytokines , Dermatitis, Atopic/genetics , Epidermis , Food Hypersensitivity/pathology , Humans , Keratinocytes/pathology , Pruritus/pathology , Skin/pathologyABSTRACT
INTRODUCTION: A large body of evidence suggests that propolis exerts antioxidant, anti-inflammatory, and antimicrobial activities, mostly ascribed to its polyphenol content. Growing evidence suggests that propolis could modulate gut microbiota exerting a positive impact on several pathological conditions. The aim of this study was to determine the in vitro impact of a poplar-type propolis extract with a standardized polyphenol content, on the composition and functionality of gut microbiota obtained from fecal material of five different donors (healthy adults, and healthy, obese, celiac, and food allergic children). METHODS: The standardized polyphenol mixture was submitted to a simulated in vitro digestion-fermentation process, designed to mimic natural digestion in the human oral, gastric, and intestinal chambers. The antioxidant profile of propolis before and after the digestion-fermentation process was determined. 16 S rRNA amplicon next-generation sequencing (NGS) was used to test the effects on the gut microbiota of propolis extract. The profile of the short-chain fatty acids (SCFA) produced by the microbiota was also investigated through a chromatographic method coupled with UV detection. RESULTS: In vitro digestion and fermentation induced a decrease in the antioxidant profile of propolis (i.e., decrease of total polyphenol content, antiradical and reducing activities). Propolis fermentation exhibited a modulatory effect on gut microbiota composition and functionality of healthy and diseased subjects increasing the concentration of SCFA. CONCLUSIONS: Overall, these data suggest that propolis might contribute to gut health and could be a candidate for further studies in view of its use as a prebiotic ingredient.
Subject(s)
Antioxidants/pharmacology , Gastrointestinal Microbiome/drug effects , Polyphenols/pharmacology , Propolis , Celiac Disease/pathology , Fatty Acids, Volatile/metabolism , Feces/microbiology , Fermentation/physiology , Food Hypersensitivity/pathology , Obesity/pathologyABSTRACT
INTRODUCTION: The increase in high-fat diet (HFD)-induced obesity and food allergy leads to an assumption that the 2 are related. This study aims to (1) systematic verification of HFD-induced obesity aggravates food allergy and (2) explore the correlation and molecular mechanisms of HFD-induced obesity promotes food allergy. METHODS: Female BALB/c mice are divided into the control group (control), the ovalbumin (OVA)-sensitized group (OVA), the HFD-induced obesity group (HFD), and HFD-induced allergic obesity group (HFD + OVA). RESULTS: In vivo data showed that HFD feed enhance clinical symptoms and intestinal mucosa villi shed on allergic mice. Moreover, we found that HFD and OVA irritation enhanced levels of mast cell degranulation and Th2 humoral response. Additionally, Western blot analysis showed the potentiation of peroxisome proliferator-activated receptor γ (PPAR γ) remarkably reduced on intestinal in HFD and OVA group, thereby inhibiting the expression of nuclear factor kappa B (NF-κB)/PPAR γ signal the phosphorylation of NF-κB P65. CONCLUSIONS: Overall, our results suggest that HFD-induced obesity is a potential risk factor for food allergy, which related to intestinal barrier destruction and inflammation through the PPAR γ/NF-κB signaling pathway.
Subject(s)
Food Hypersensitivity/etiology , Food Hypersensitivity/metabolism , Gastroenteritis/etiology , Gastroenteritis/metabolism , Intestinal Mucosa/immunology , Intestinal Mucosa/metabolism , Obesity/complications , Animals , Biomarkers , Cytokines/metabolism , Diet, High-Fat , Disease Models, Animal , Disease Susceptibility , Female , Food Hypersensitivity/pathology , Gastroenteritis/pathology , Immunohistochemistry , Intestinal Mucosa/pathology , Mice , NF-kappa B/metabolism , Obesity/etiology , PPAR gamma , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolismABSTRACT
Atopic dermatitis (AD) is one of the most prevalent inflammatory disease among non-fatal skin diseases, affecting up to one fifth of the population in developed countries. AD is characterized by recurrent pruritic and localized eczema with seasonal fluctuations. AD initializes the phenomenon of atopic march, during which infant AD patients are predisposed to progressive secondary allergies such as allergic rhinitis, asthma, and food allergies. The pathophysiology of AD is complex; onset of the disease is caused by several factors, including strong genetic predisposition, disrupted epidermal barrier, and immune dysregulation. AD was initially characterized by defects in the innate immune system and a vigorous skewed adaptive Th2 response to environmental agents; there are compelling evidences that the disorder involves multiple immune pathways. Symptomatic palliative treatment is the only strategy to manage the disease and restore skin integrity. Researchers are trying to more precisely define the contribution of different AD genotypes and elucidate the role of various immune axes. In this review, we have summarized the current knowledge about the roles of innate and adaptive immune responsive cells in AD. In addition, current and novel treatment strategies for the management of AD are comprehensively described, including some ongoing clinical trials and promising therapeutic agents. This information will provide an asset towards identifying personalized targets for better therapeutic outcomes.
Subject(s)
Adaptive Immunity , Dermatitis, Atopic/immunology , Epidermis/immunology , Immunity, Innate , Th2 Cells/immunology , Animals , Asthma/etiology , Asthma/immunology , Asthma/pathology , Dermatitis, Atopic/complications , Dermatitis, Atopic/pathology , Epidermis/pathology , Food Hypersensitivity/etiology , Food Hypersensitivity/immunology , Food Hypersensitivity/pathology , Humans , Rhinitis, Allergic/etiology , Rhinitis, Allergic/immunology , Rhinitis, Allergic/pathology , Th2 Cells/pathologyABSTRACT
BACKGROUND: Food allergy reactions range from mild to severe with differences in age appearing to be an important factor associated with reaction severity. OBJECTIVE: To define differences in oral food challenge (OFC) reaction severity in pediatric patients from infancy to adolescence using objective clinical outcomes and standardized reaction grading tools. METHODS: Retrospective review of all positive OFC results at 2 large institutions between September 2016 and February 2019. Reaction severity was defined by presence of cardiovascular, neurologic, lower respiratory, or laryngeal symptoms, epinephrine requirement, and grading using 2 established food allergy reaction scales. RESULTS: Infants and toddlers had fewer reactions involving cardiovascular, neurologic, lower respiratory, or laryngeal symptoms compared with older age groups. Epinephrine was also required less frequently during reactions in infants and toddlers, compared with older age groups. There was no difference in reaction severity in infants and toddlers based on clinical history of eczema. Increasing age was significantly correlated with increased epinephrine requirement (R2 = 0.12, P = .002), elevated Consortium of Food Allergy Research score (R2 = .012, P = .003), and approached significance for increased Practical Allergy score (R2 = .005, P = .05). History of asthma and sesame allergy were identified to be positively correlated with more severe reactions. CONCLUSION: Infants and young toddlers have less severe reactions during OFCs compared with older age groups supporting early food introduction practices. In children under 12 months of age, severe reactions are most rare calling into question screening practices using specific allergy testing before food introduction. Standardized reaction grading tools may be valuable instruments to categorize reaction severity during OFCs.
Subject(s)
Allergens/administration & dosage , Desensitization, Immunologic/methods , Food Hypersensitivity/diagnosis , Food Hypersensitivity/pathology , Severity of Illness Index , Administration, Oral , Adolescent , Allergens/immunology , Anaphylaxis/diagnosis , Child , Child, Preschool , Female , Food/adverse effects , Food Hypersensitivity/immunology , Humans , Infant , Male , Retrospective StudiesABSTRACT
Ticks and the pathogens they transmit, including bacteria, viruses, protozoa, and helminths, constitute a growing burden for human and animal health worldwide. The ability of some animal species to acquire resistance to blood-feeding by ticks after a single or repeated infestation is known as acquired tick resistance (ATR). This resistance has been associated to tick-specific IgE response, the generation of skin-resident memory CD4+ T cells, basophil recruitment, histamine release, and epidermal hyperplasia. ATR has also been associated with protection to tick-borne tularemia through allergic klendusity, a disease-escaping ability produced by the development of hypersensitivity to an allergen. In addition to pathogen transmission, tick infestation in humans is associated with the α-Gal syndrome (AGS), a type of allergy characterized by an IgE response against the carbohydrate Galα1-3Gal (α-Gal). This glycan is present in tick salivary proteins and on the surface of tick-borne pathogens such as Borrelia burgdorferi and Anaplasma phagocytophilum, the causative agents of Lyme disease and granulocytic anaplasmosis. Most α-Gal-sensitized individuals develop IgE specific against this glycan, but only a small fraction develop the AGS. This review summarizes our current understanding of ATR and its impact on the continuum α-Gal sensitization, allergy, and the AGS. We propose that the α-Gal-specific IgE response in humans is an evolutionary adaptation associated with ATR and allergic klendusity with the trade-off of developing AGS.
Subject(s)
Anaplasmosis/immunology , Disease Resistance , Food Hypersensitivity/immunology , Hyperplasia/immunology , Lyme Disease/immunology , Ticks/immunology , Tularemia/immunology , Allergens/administration & dosage , Anaplasma phagocytophilum/immunology , Anaplasma phagocytophilum/pathogenicity , Anaplasmosis/etiology , Anaplasmosis/pathology , Anaplasmosis/prevention & control , Animals , Basophils/immunology , Basophils/pathology , Borrelia burgdorferi/immunology , Borrelia burgdorferi/pathogenicity , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/pathology , Epidermis/immunology , Epidermis/parasitology , Food Hypersensitivity/etiology , Food Hypersensitivity/pathology , Food Hypersensitivity/prevention & control , Host-Parasite Interactions/immunology , Humans , Hyperplasia/etiology , Hyperplasia/pathology , Immunoglobulin E/biosynthesis , Immunologic Memory , Lyme Disease/etiology , Lyme Disease/pathology , Lyme Disease/prevention & control , Ticks/chemistry , Ticks/pathogenicity , Tularemia/etiology , Tularemia/pathology , Tularemia/prevention & controlABSTRACT
AIMS: Epidemiology shows that gender affects the incidence of food allergy. However, there is a lack of evidence of gender differences in food allergies and little is known about the mechanisms. The aim of this study was to excavate potential reasons for gender differences in food allergy based on estrogen. MAIN METHODS: Female and male BALB/c mice sensitized with ovalbumin (OVA) were established to analyze the difference in food allergy. The systemic anaphylactic, including OVA-specific IgE, OVA-specific IgG, histamine, and cytokines, was assessed using an enzyme-linked immunosorbent assay (ELISA). ELISA also detected the estradiol in serum. Western blotting and immunofluorescence were used to detect the estrogen receptor. Peroxisome proliferator-activated receptor gamma (PPARγ) implicated in immune homeostasis and nuclear factor kappa-B (NF-κB) were determined by western blotting. Immunohistochemistry and hematoxylin-eosin (H&E) staining were used to detect zonula occludens-1 (ZO-1), tryptase, forkhead box protein P3 (Foxp3), and intestinal morphology, respectively. KEY FINDINGS: Female mice were more vulnerable to food allergy. Female mice treated with OVA did exhibit more serious systemic anaphylaxis than male mice. We observed increased levels of estradiol in serum, estrogen receptor, NF-κB, and decreased levels of PPAR γ in female mice. Furthermore, the intestinal mucosal integrity and intestinal permeability were more impaired in female mice treated with OVA than male mice. SIGNIFICANCE: Clarify the mechanism of gender differences in food allergies can provide targets in female mice and provide personalized diagnosis, management, and treatment of food allergy for female mice.
Subject(s)
Food Hypersensitivity/pathology , Inflammation/pathology , Intestines/pathology , NF-kappa B/analysis , PPAR gamma/analysis , Animals , Female , Food Hypersensitivity/etiology , Inflammation/etiology , Male , Mice , Mice, Inbred BALB C , Sex Characteristics , Sex FactorsABSTRACT
OBJECTIVE: Although a number of articles have described the psychosocial impact of raising a child with a food allergy, recent attempts at synthesizing this literature have been narrow in focus or methodologically limited. Consequently, this study aimed to synthesize both the quantitative and qualitative literature to achieve a better understanding of the psychosocial and financial burdens faced by families who raise children with food allergy. DATA SOURCES: Searches were performed on PubMed, Scopus, PsycInfo, and Cumulative Index to Nursing and Allied Health Literature databases for articles related to the psychosocial and financial burden experienced by individuals who care for a child with food allergy. STUDY SELECTIONS: English language, original research articles were included in this review. RESULTS: A total of 54 articles were deemed eligible for review. Results from the quantitative literature revealed that parents of children with food allergy (ie, food allergy and food protein-induced enterocolitis, proctocolitis, and enteropathy) consistently reported lower quality of life than their comparison groups. Within-group analyses suggest that this burden is increased for parents who manage multiple food allergies, severe food allergy, and comorbid allergic conditions. Thematic synthesis of the qualitative literature suggests that the psychosocial burden shouldered by parents of children with food allergy stems, in part, from the unpredictable threat of exposure and the practical and social burdens of managing a food allergy. In addition to psychosocial burdens, a small but growing body of literature suggests that families with food allergy also incur greater financial costs. CONCLUSION: Findings suggest that pediatric food allergy imposes considerable burdens on parents both quantitatively and qualitatively.
Subject(s)
Caregiver Burden/psychology , Food Hypersensitivity/economics , Food Hypersensitivity/psychology , Parents/psychology , Quality of Life/psychology , Adolescent , Child , Child, Preschool , Female , Food/adverse effects , Food Hypersensitivity/pathology , Humans , Infant , Male , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: Substantial discrepancies among anaphylaxis severity scores may delay epinephrine administration. OBJECTIVE: The study aims to develop a transparent severity grading system of food-induced acute allergic reactions with a decision model for epinephrine use. METHODS: The natural course of 315 acute food-induced allergic reactions in children hospitalized at the Allergology department between May 2016 and July 2019 owing to follow-up treatment and allergy diagnostics was evaluated. The severity of episodes was classified according to the 5 most accepted grading systems. The interrater reliability of classification between anaphylaxis severity scores was assessed. All symptoms were grouped into a heat map according to their real-life incidence and clinical relevance. Based on the heat map analysis, a severity grading system of food-induced acute allergic reactions in children with the epinephrine administration decision model was created. RESULTS: Data from 259 food-induced anaphylaxis episodes in 157 children were included in the analysis. Comparing the grading systems, we observed a 24.7% to 70.2% disagreement between severity scores. The heat map illustrated a strong association between 29 symptoms and their categorization. A new severity grading system was developed and a 2-stage decision model was proposed: "epinephrine yes" (any rapidly progressing symptoms, even mild ones or from 1 organ system; any symptoms from more than 1 organ system; or every grade of anaphylaxis), and "epinephrine available and prepared to use" (nonprogressing mild systemic allergic reaction from 1 system area only; no anaphylaxis). CONCLUSION: A new severity grading system of food-induced acute allergic reactions in children could serve as a clinical tool for health care professionals to avoid epinephrine administration delay.
Subject(s)
Decision Support Techniques , Epinephrine/therapeutic use , Food Hypersensitivity/diagnosis , Food Hypersensitivity/drug therapy , Severity of Illness Index , Adolescent , Allergens/immunology , Anaphylaxis/diagnosis , Anaphylaxis/drug therapy , Anaphylaxis/pathology , Child , Child, Preschool , Epinephrine/administration & dosage , Female , Food Hypersensitivity/pathology , Humans , Infant , Infant, Newborn , MaleABSTRACT
Children undergoing colonoscopy and mucosal biopsies may show increased colonic mucosal eosinophils, which may or may not be associated with inflammatory bowel disease. There is not much clinical data on American children who have isolated increased colonic mucosal eosinophils. We sought to study the clinical correlates of children without inflammatory bowel disease who show increased mucosal eosinophils to understand their clinical presentation, etiological associations, and outcome. A retrospective analysis of children seen at a tertiary-level Children's hospital was performed by reviewing their medical charts and extracting pertinent data. There were 110 children in the study who had increased colonic mucosal eosinophils. Most children presented with abdominal pain, but several of them also had constipation, blood in stools, and diarrhea. Food allergies, irritable bowel syndrome, asthma, and lactase deficiency were the top four conditions present in these patients. Pathology of the colonic distribution revealed involvement of more than two colonic regions in 86% of the subjects, and only two subjects showing epithelial or crypt involvement by eosinophils. All subjects had a good outcome. Children with colonic mucosal eosinophilia (CME) who do not have an inflammatory bowel disease most frequently present with abdominal pain and primarily an increase of lamina propria eosinophils in two or more colonic regions. Based on the etiological associations we noted in the study, a work-up of children with CME may encompass detailed history for functional gastrointestinal disorders and lactose intolerance, testing for food and environmental allergies, stool examination for parasites, and peripheral blood counts. Almost all children had resolution of symptoms in the studied period suggesting that CME in children has a good clinical outcome.
Subject(s)
Colon/pathology , Colonic Diseases/pathology , Eosinophilia/pathology , Eosinophils/pathology , Intestinal Mucosa/pathology , Abdominal Pain/etiology , Adolescent , Age Factors , Biopsy , Carbohydrate Metabolism, Inborn Errors/complications , Carbohydrate Metabolism, Inborn Errors/pathology , Child , Child, Preschool , Colonic Diseases/etiology , Colonoscopy , Constipation/etiology , Diarrhea/etiology , Eosinophilia/etiology , Female , Food Hypersensitivity/complications , Food Hypersensitivity/pathology , Humans , Infant , Lactase/deficiency , Male , Prognosis , Retrospective Studies , Risk FactorsABSTRACT
OBJECTIVE: To provide a concise summary of the current literature regarding gastrointestinal immunopathology of food protein-induced enterocolitis syndrome (FPIES) and other non-immunoglobulin E (IgE)-mediated food allergic diseases. DATA SOURCES: Data were extracted from PubMed, MEDLINE, and ScienceDirect databases. STUDY SELECTIONS: Original articles, review articles, and guidelines published in the past 5 years in peer-reviewed journals were first summarized. The original articles cited were then reviewed and relevant results were extracted. RESULTS: Patients with FPIES and non-IgE-mediated food allergic diseases developed vomiting, diarrhea, and food aversion expelled food allergen from their bodies. Aside from T helper type 2 (TH2) immunity, TH1, TH17, innate immunity, and epithelial mucosal barrier defect were also found to be important in the pathogenesis. Eosinophils, widely identified in the biopsy samples, were key players or were late-recruited cells for tissue repairs in those diseases. Intestinal dysbiosis and their metabolites stimulated enterochromaffin cells or enteroendocrine cells to produce serotonin, interfering with intestinal motility and subsequently affecting brain function. FPIES and non-IgE-mediated food allergic diseases were likely part of the atopic march. Allergic inflammation in intestinal mucosa might result in subsequent inflammation in the airway mucosa, suggesting the theory of "one mucosa, one disease." CONCLUSION: The immune responses of FPIES and non-IgE-mediated food allergic diseases were not limited to the gastrointestinal tract, but also trigger wider inflammatory responses beyond it. Further research will be required to determine the systemic effect and intestinal microbiome of those diseases.
Subject(s)
Dietary Proteins/immunology , Enterocolitis/pathology , Food Hypersensitivity/pathology , Gastrointestinal Tract/immunology , Immunity, Innate/immunology , Allergens/immunology , Enterocolitis/immunology , Food Hypersensitivity/immunology , Humans , Respiratory System/immunology , Th1 Cells/immunology , Th17 Cells/immunology , Th2 Cells/immunologyABSTRACT
OBJECTIVE: Food protein-induced enterocolitis syndrome (FPIES) is typically diagnosed based on a characteristic clinical history; however, an oral food challenge (OFC) may be necessary to confirm the diagnosis or evaluate for the development of tolerance. FPIES OFC methods vary globally, and there is no universally agreed upon protocol. The objective of this review is to summarize reported FPIES OFC approaches and consider unmet needs in diagnosing and managing FPIES. DATA SOURCES: PubMed database was searched using the keywords food protein-induced enterocolitis syndrome, oral food challenge, cow milk allergy, food allergy, non-immunoglobulin E-mediated food allergy and FPIES. STUDY SELECTIONS: Primary and review articles were selected based on relevance to the diagnosis of FPIES and the FPIES OFC. RESULTS: We reviewed the history of FPIES and the evolution and variations in the FPIES OFC. A summary of current literature suggests that most patients with FPIES will react with 25% to 33% of a standard serving of the challenged food, there is little benefit to offering a divided dose challenge unless there is suspicion of specific immunoglobulin E to the food being challenged, reactions typically appear within 1 to 4 hours of ingestion, and reactions during OFC rarely result in emergency department or intensive care unit admission. CONCLUSION: International standardization in the FPIES OFC approach is necessary with particular attention to specific dose administration across challenged foods, timing between the patient's reaction and offered OFC to verify tolerance, patient safety considerations before the OFC, and identification of characteristics that would indicate home reintroduction is appropriate.
Subject(s)
Dietary Proteins/immunology , Enterocolitis/diagnosis , Enterocolitis/pathology , Food Hypersensitivity/diagnosis , Food Hypersensitivity/pathology , Allergens/immunology , Enterocolitis/immunology , Food Hypersensitivity/immunology , Humans , Immune Tolerance/immunology , Milk Hypersensitivity/immunology , Milk Hypersensitivity/pathology , Wheat Hypersensitivity/immunology , Wheat Hypersensitivity/pathologyABSTRACT
OBJECTIVE: To explore the relationship among gastrointestinal (GI) symptoms, immune response, and autonomic nervous system (ANS) in food protein-induced enterocolitis syndrome (FPIES) in relation to the current understanding of disease phenotype and pathogenesis. DATA SOURCES: Relevant studies related to FPIES, GI symptomatology, and ANS were reviewed. Literature search was performed using PubMed, with keyword combinations including but not limited to FPIES, allergic GI disorders, ANS, autonomic dysfunction, dysautonomia, GI, diarrhea, vomiting, neuroimmune, and clinical phenotyping tools. STUDY SELECTIONS: Peer-reviewed case-control studies, observational studies, reviews and guidelines, and systematic reviews related to FPIES and ANS were selected for review. RESULTS: There is limited research directly relating GI symptoms and FPIES to the ANS and immunologic response. To support the proposed mechanisms of action related to patient symptoms, studies relevant to coexisting GI-autonomic processes and FPIES immunologic triggers were examined. These related disease processes were extrapolated to FPIES based on the current knowledge of FPIES phenotype and pathogenesis. CONCLUSION: The etiology of FPIES and the underlying mechanisms triggering symptoms are not well understood. On the basis of the exaggerated GI symptoms and hemodynamic response observed, the ANS likely plays an important role in FPIES, possibly as a compensatory response. The trigger for this cascade of symptoms may be related to the disruption of immunologic homeostasis that typically contributes to immune tolerance. To more accurately evaluate FPIES pathophysiology necessitates understanding the diverse spectrum of presenting symptoms. A consistent and comprehensive symptom assessment tool may improve our understanding of this dynamic relationship.
Subject(s)
Dietary Proteins/immunology , Enterocolitis/pathology , Food Hypersensitivity/pathology , Gastrointestinal Tract/pathology , Allergens/immunology , Enterocolitis/immunology , Food Hypersensitivity/immunology , Humans , Immunity, Innate/immunology , Vomiting/drug therapySubject(s)
Dietary Proteins/immunology , Enterocolitis/diagnosis , Food Hypersensitivity/diagnosis , Child , Child, Preschool , Chile , Enterocolitis/immunology , Enterocolitis/pathology , Food Hypersensitivity/immunology , Food Hypersensitivity/pathology , Gastrointestinal Tract/pathology , Humans , Infant , Infant, Newborn , Retrospective StudiesABSTRACT
OBJECTIVE: Food protein-induced enterocolitis syndrome (FPIES) is a condition with heterogeneous features (ie, age at presentation, severity, food triggers, comorbidities) and is not as rare as initially believed. In the last few years, the first population-based epidemiologic study, few prospective birth cohort evaluating FPIES prevalence, and several larger (>100 patients) studies have been published, making epidemiologic estimation more reliable. In this review, we report on the available data on the epidemiology of FPIES. DATA SOURCES: PubMed review using the following words: FPIES, epidemiology, and prevalence. STUDY SELECTIONS: The review focused on the population-based epidemiologic study, few prospective birth cohort evaluating FPIES prevalence, and several larger (>100 patients) studies. RESULTS: We identified 8 population or cohort studies. CONCLUSION: FPIES is not rare in both children and adults and may affect as many as 900,000 people in the United States alone. Most children and adult with FPIES seem to react to 1 to 2 foods; however, they may need further diet restriction owing to high level of comorbidity with immunoglobulin E-mediated food allergies and eosinophilic esophagitis. Globally, cow's milk, rice/oat, and seafood seem to be the most common triggers.
Subject(s)
Dietary Proteins/immunology , Enterocolitis/epidemiology , Food Hypersensitivity/epidemiology , Adult , Allergens/immunology , Child , Comorbidity , Enterocolitis/immunology , Enterocolitis/pathology , Female , Food Hypersensitivity/immunology , Food Hypersensitivity/pathology , Humans , Male , Risk FactorsABSTRACT
Food is simultaneously a source of essential nutrients and a potential source of lethal toxins and pathogens. Consequently, multiple sensory mechanisms evolved to monitor the quality of food based on the presence and relative abundance of beneficial and harmful food substances. These include the olfactory, gustatory, and gut chemosensory systems. Here we argue that, in addition to these systems, allergic immunity plays a role in food quality control by mounting allergic defenses against food antigens associated with noxious substances. Exaggeration of these defenses can result in pathological food allergy.
Subject(s)
Food Hypersensitivity/pathology , Food/adverse effects , Allergens/immunology , Food Hypersensitivity/immunology , Humans , Immunity , Models, Biological , Quality ControlABSTRACT
OBJECTIVE: Although food protein-induced enterocolitis syndrome (FPIES) was first described approximately 50 years ago and research is increasing, there are still considerable unmet needs in FPIES. This article catalogs the areas of progress and areas for further research. DATA SOURCES: Through our personal experiences in caring for patients with FPIES, our personal research, and a review of the existing FPIES literature as indexed in PubMed, we explored what is known and what is needed in FPIES. STUDY SELECTIONS: The studies that have improved the knowledge of FPIES, defined phenotypes, allowed for better-informed management of FPIES, and laid the groundwork for further research. RESULTS: Further research is needed in the areas of prevalence, natural history, trigger foods, threshold doses, how and when to perform oral food challenges, and immunopathogenesis of this disorder. Development of a biomarker and determination of the best method to treat reactions is also needed. Furthermore, FPIES has a substantial psychosocial and economic impact on families, and more research is needed in developing and implementing ameliorating strategies. CONCLUSION: By partnering together, health care providers, advocacy organizations, and families can continue to advance our understanding and improve the care of patients and families living with FPIES.
Subject(s)
Enterocolitis/diagnosis , Enterocolitis/pathology , Food Hypersensitivity/diagnosis , Food Hypersensitivity/pathology , Adult , Allergens/immunology , Caregivers/psychology , Child , Child, Preschool , Dietary Proteins/immunology , Enterocolitis/immunology , Food Hypersensitivity/immunology , HumansABSTRACT
Up to 20% of people worldwide develop gastrointestinal symptoms following a meal1, leading to decreased quality of life, substantial morbidity and high medical costs. Although the interest of both the scientific and lay communities in this issue has increased markedly in recent years, with the worldwide introduction of gluten-free and other diets, the underlying mechanisms of food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response that leads to the production of dietary-antigen-specific IgE antibodies in mice, which are limited to the intestine. Following subsequent oral ingestion of the respective dietary antigen, an IgE- and mast-cell-dependent mechanism induced increased visceral pain. This aberrant pain signalling resulted from histamine receptor H1-mediated sensitization of visceral afferents. Moreover, injection of food antigens (gluten, wheat, soy and milk) into the rectosigmoid mucosa of patients with irritable bowel syndrome induced local oedema and mast cell activation. Our results identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders.