Materiały źródłowe

• #1 Food allergy: an updated review on pathogenesis, diagnosis, prevention and management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8023067/

  Food allergy (FA) is an adverse immunologic response triggered by normally innocuous food protein antigens. FA can be broadly classified into those that are IgE mediated, those that are mediated by both IgE-dependent and IgE-independent pathways (mixed), and those that are not IgE mediated Immunoglobulin E. (IgE)-mediated reaction is characterized by rapid onset of symptoms involving respiratory, gastrointestinal, dermatologic and cardiovascular systems; mixed and non-IgE-mediated has a longer onset and manifests primary in the gastrointestinal tract and skin. […] The breakdown of immunologic and clinical tolerance to an ingested food is the trigger for FA; this results in IgE-, non-IgE- or mixed IgE- and non-IgE-mediated reactions. IgE-mediated FA is characterized by immediate clinical manifestations, due to the release of mediators triggered by the bonding of IgE antibodies, mast cells and basophils. Non IgE-mediated FA, is due to T-cell driven inflammatory responses.

• #2 Food allergy: immune mechanisms, diagnosis and immunotherapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5123910/

  Food allergy is a pathological, potentially deadly, immune reaction triggered by normally innocuous food protein antigens. […] Food allergy is a pathological reaction of the immune system triggered by the ingestion of a food protein antigen. Exposure to very small amounts of allergenic foods can trigger clinical symptoms such as gastrointestinal disorders, urticaria and airway inflammation, ranging in severity from mild to life-threatening. […] In individuals with food allergy, sensitization to food allergens results in inappropriate inflammatory immune responses to common foods. […] Many clinical trials in food allergy aim to establish functional immune tolerance in place of this sensitization. This is defined by clinical endpoints in a clinical trial after a period of withdrawal from therapy, otherwise known as sustained unresponsiveness.

• #3 Pathogenesis of food allergy – UpToDate

  https://www.uptodate.com/contents/pathogenesis-of-food-allergy

  Pathogenesis of food allergy […] Tolerance is the normal immune response to the food an individual eats over a lifetime. Food allergy is an abnormal immune reaction consisting of hypersensitivity to food components, most commonly proteins. […] This topic will focus on food allergy due to primary sensitization through the gut and will review organization of the gut immune system and factors that influence oral tolerance induction. Theories addressing the increasing prevalence of food allergy are briefly mentioned. […] Hygiene hypothesis – Early life exposure to infectious pathogens, as well as normal gut microbiota, may influence the development of the immune system away from a T helper type 2 (Th2) and towards a T regulatory cell (Treg) response. Better hygiene, resulting in less microbial exposure, may lead to an increase in atopic disease.

• #4 Food Allergy – Immunology; Allergic Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/immunology-allergic-disorders/allergic-autoimmune-and-other-hypersensitivity-disorders/food-allergy

  Food allergy is an exaggerated immune response to dietary components, usually proteins. […] In general, food allergy is mediated by IgE, T cells, or both: […] IgE-mediated allergy (eg, urticaria, asthma, anaphylaxis) is acute in onset, usually develops during infancy, and occurs most often in people with a strong family history of atopy. […] T-cell-mediated allergy (eg, dietary protein gastroenteropathies, celiac disease) manifests gradually and is chronic; it is most common among infants and children. […] Allergies mediated by both IgE and T cells (eg, atopic dermatitis, eosinophilic gastroenteropathy) tend to be delayed in onset or chronic. […] Oral allergy syndrome (pollen food allergy syndrome) is caused by proteins in pollens and foods that cross-react (frequently raw fruits and vegetables and nuts).

• #5 Food Allergies: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/135959-overview

  Food allergies are immunologically mediated adverse reactions to foods that are often but not exclusively IgE mediated. Any food protein, and sometimes carbohydrate moieties, can trigger an allergic response, and allergic reactions to a large number of foods have been documented; however, only a small group of foods account for the majority of these reactions. […] IgE antibody-mediated responses are the most widely recognized form of food allergy and account for most reactions. IgE-mediated reactions are generally acute, and most reactions occur within minutes of ingesting the offending food. […] Patients with atopy produce IgE antibodies to specific epitopes (areas of the protein or carbohydrate moieties) of one or more food allergens. These antibodies bind to high-affinity IgE receptors on circulating basophils and tissue mast cells present throughout the body, including in the skin, gastrointestinal tract, and respiratory tract.

• #6

  https://link.springer.com/article/10.1007/s12016-018-8710-3

  Food allergies are defined as adverse immune responses to food proteins that result in typical clinical symptoms involving the dermatologic, respiratory, gastrointestinal, cardiovascular, and/or neurologic systems. […] IgE-mediated food-allergic disease differs from non-IgE-mediated disease because the pathophysiology results from activation of the immune system, causing a T helper 2 response which results in IgE binding to Fc receptors on effector cells like mast cells and basophils. […] The activation of these cells causes release of histamine and other preformed mediators, and rapid symptom onset, in contrast with non-IgE-mediated food allergy which is more delayed in onset. […] The immune system plays an integral role in the maintenance of tolerance to innocuous antigens. […] IgE-mediated food allergies occur as a result of a loss of integrity in the key immune components that maintain a state of tolerance and prevent benign food antigens from being recognized as pathogens.

• #7 Food Allergies: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/135959-overview

  Subsequent allergen exposure binds and cross links IgE antibodies on the cell surface, resulting in receptor activation and intracellular signaling that initiates the release of inflammatory mediators (eg, histamine) and synthesis of additional factors (eg, chemotactic factors, cytokines) that promote allergic inflammation. The effects of these mediators on surrounding tissues result in vasodilation, smooth muscle contraction, and mucus secretion, which, in turn, are responsible for the spectrum of clinical symptoms observed during acute allergic reactions to food. […] T-cell-mediated responses to food allergens may also mediate allergic responses, particularly in disorders with delayed or chronic symptoms. For example, food protein-induced enterocolitis syndrome (FPIES), a gastrointestinal food allergy, appears to be mediated by T-cell production of the cytokine tumor necrosis factor (TNF)-alpha.

• #8 The immunopathogenesis of cow’s milk protein allergy (CMPA) | Italian Journal of Pediatrics | Full Text

  https://ijponline.biomedcentral.com/articles/10.1186/1824-7288-38-35

  The immunological mechanism that lead to the development of cows milk allergy (or Cows Milk Protein Allergy- CMPA) is not still clarified. There are different mechanisms that contribute to the pathogenesis and the main two described mechanisms at the basis of this disease refer to IgE- and not-IgE- reactions. […] IgE-mediated reactions are based on simply immunological mechanisms that are better identified than not-IgE-mediated ones. […] IgE-mediated CMAP is characterized by two stages: the first, of sensibilization, develops when the immune system is programmed in an aberrant way, so that IgE antibodies against cow milk proteins are secreted. […] The interaction between APC and T lymphocytes promotes the modulation and the activation of B lymphocytes. […] The pathogenesis of non-IgE mediated reactions is supported by different theories: reactions mediated by Th1 cells, interactions between T lymphocytes, mast cells and neurons that alters the function of the smooth muscle and the intestinal motility.

• #9

  https://link.springer.com/article/10.1007/s12016-018-8710-3

  More specifically, oral tolerance to foods is defined as the crossing of food antigen across the mucosal barrier, processing by dendritic cells in a non-activated state, and the induction of suppressive cytokines, such as interleukin 10, by those antigen-presenting cells. […] This in turn results in the differentiation of nave T cells into T regulatory cells and suppression of food antigen-specific Th2 cells, as well as increased IgA and IgG4 production and a decrease in IgE by B cells. […] Sensitization is defined as the state of having detectable food-specific IgE which can be a precursor to the development of clinical food allergy. […] It occurs when food crosses disrupted barrier and as a result of this disruption, danger signals and inflammatory cytokines are released which activate dendritic cells into phenotypes that are normally acquired during the defense against pathogens.

• #10 Food allergy: an updated review on pathogenesis, diagnosis, prevention and management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8023067/

  Sensitization is a condition of having detectable food antigen specific IgE which can precede (or sometimes follows if clinical tolerance develops) the development of clinical FA. Immunologic mechanisms leading to the sensitization start with the first contact when the allergen occurs. Disruption of food tolerance is a consequence of epithelial barrier damage following the exposure to many factors such as pathogen-associated molecular patterns (PAMPs). […] The activated dendritic cells in turn activate naive T cells into acquiring a T helper cells 2 (Th2) phenotype, which promotes inflammatory signals, inducing food Ag-specific B cells to class switch and produce food antigen-specific IgE. […] Factors breaking immune tolerance through the skin include skin barrier defects consequent to fillagrins mutations, a protein essential for skin integrity, damage to the skin, microbial adjuvants such as staphylococcus enterotoxin B. All these factors induce an innate inflammatory skin response causing sensitization.

• #11

  https://link.springer.com/article/10.1007/s12016-018-8710-3

  These activated dendritic cells in turn activate nave T cells into acquiring a T helper cell 2 (Th2) phenotype, which in turn promote inflammatory signals which induce food Ag-specific B cells to class switch and produce food antigen-specific IgE. […] In short, sensitization is mistaken identification of food antigen as pathogen. […] All patients with IgE-mediated food allergies are sensitized to food allergen. […] The five components of the immune system, the epithelium, innate immune cells, T cells, B cells, and effector cells (mast cells, eosinophils, and basophils), can either promote tolerance to food antigens or sensitization, leading to allergic manifestations. […] Genetic and environmental factors can influence the immune system. […] As more is discovered about these influences, the underlying pathophysiology of IgE-mediated food allergy may be altered to promote tolerance or a state of desensitization (absence of clinical symptoms on exposure to food).

• #12 Food allergy – Wikipedia

  https://en.wikipedia.org/wiki/Food_allergy

  If later exposure to the same allergen occurs, the allergen can bind to the IgE molecules held on the surface of the mast cells or basophils. Cross-linking of the IgE and Fc receptors occurs when more than one IgE-receptor complex interacts with the same allergenic molecule and activates the sensitized cell. Activated mast cells and basophils undergo a process called degranulation, during which they release histamine and other inflammatory chemical mediators (cytokines, interleukins, leukotrienes, and prostaglandins) from their granules into the surrounding tissue causing several systemic effects, such as vasodilation, mucous secretion, nerve stimulation, and smooth-muscle contraction.

• #13 Food allergy: an updated review on pathogenesis, diagnosis, prevention and management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8023067/

  Oral tolerance consists in the systemic suppression of cellular and humoral immune response to an antigen first encountered in the gastrointestinal (GI) tract, although immune tolerance can be induced by other routes such as airways and intact skin. Physical barriers, digestive processes, specific immune cells and immune modulation determine gastrointestinal tracts ability to develop oral tolerance. Specialized GI cells (microfold, intestinal epithelial, and dendritic cells) play an essential role in antigen presentation and oral tolerance development, process food proteins outliving the digestive process. Dendritic cells play a central role in induction and maintenance of tolerance to food antigens. […] The subsequent actions of both T and B cells are suppressed by TGF-beta and the latter also aids the production of secretory IgA; T-cell anergy is induced by IL-10 which also sustains Treg populations. The switching of B-cell class to produce secretory IgA is also partially provided by IL-10.

• #14 Food allergy: immune mechanisms, diagnosis and immunotherapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5123910/

  The mechanisms of desensitization are not well understood and may differ from those of the healthy state of immune tolerance. […] The deduction of disease mechanisms lies at the fore-front of food allergy research. […] The establishment of immune tolerance to orally administered antigens is a subject of intensive study. […] The healthy immune system is tolerant to foods, characterized by a sustained (that is, memory) unresponsiveness towards potential food allergens even in the absence of regular allergen exposure. […] Immune tolerance is an active process that begins with the uptake of potential food antigens in the small intestine, which contains much of the gut-associated lymphoid tissue (GALT). […] DC-mediated tolerance to food antigens can be reprogrammed by inflammatory stimuli to give rise to food-allergic immune responses mediated by TH2 cells, as well as by additional cell types.

• #15 AAIR :: Allergy, Asthma & Immunology Research

  https://e-aair.org/DOIx.php?id=10.4168/aair.2009.1.1.19

  Food allergies are adverse immune reactions to food proteins that affect up to 6% of children and 3-4% of adults. […] Advances have been made in the understanding of how these factors interact in the pathophysiology of food allergy. […] The mechanisms by which ingested proteins are able to interact with unique populations of antigen presenting cells leading to suppression of cellular and humoral immune responses has been termed oral tolerance. […] Loss of oral tolerance can occur or may be bypassed by antigen presentation via alternative routes, such as through cutaneous exposures or via the respiratory tract. […] Breakdown of oral tolerance can also occur as a result of defective regulatory T cells. […] Several host factors can influence the development of food allergies. […] Gastric digestion normally serves to breakdown food proteins, and in many cases destroys immunogenic epitopes in the process.

• #16 Food allergy: Mechanisms, diagnosis, and management – Karnataka Paediatric Journal

  https://iap-kpj.org/food-allergy-mechanisms-diagnosis-and-management/

  Food antigens are generally weak immunogens. The antigen presenting cells in the GI tract are said to be non-professional and are not capable of eliciting a T cell response. The Treg (T regulatory) cells as well as gut flora also play a role in the propagation of oral tolerance. Exclusive breastfeeding also promotes the development of oral tolerance. […] The microbiota inhabiting the normal healthy gut is predominantly Gram negative and shed endotoxin, which through a process activates luminal B cell to preferentially produce IgA and IgG antibodies and thus maintain the integrity of mucosal immunity. On the other hand, disturbance of normal healthy microbiota, that is, dysbiosis, will activate luminal B cells to preferentially produce IgE in place of IgA and IgG and increase susceptibility to allergic diseases.

• #17 Natural course of IgE-mediated food allergy in children

  https://www.e-cep.org/journal/view.php?doi=10.3345/cep.2022.01004

  Interleukin (IL)-10 suppresses Th2 immune reactions and allergic inflammation by reducing IgE production and promoting allergen-specific IgG4 responses. […] Evidence of markers predicting the resolution or persistency of food allergy remains insufficient today. […] The current leading treatment for modifying the natural course of food allergy is oral immunotherapy, an allergen-specific approach based on progressive incremental ingestion of the food allergen doses until a daily maintenance dosage is reached to achieve desensitization. […] To provide the optimal treatment to patients with food allergy and help improve their quality of life, it is essential that clinicians understand the natural course of individual food allergies.

• #18 The Role of Skin Barrier in the Pathogenesis of Food Allergy

  https://www.mdpi.com/2227-9067/2/3/382

  Epidemiologic data suggests that sensitization to peanut protein can occur in children via exposure of inflamed skin to peanut oils. […] The importance of filaggrin deficiency in allergic sensitization has been shown in several murine studies using the filaggrin loss of function mutation. […] In food allergy, the impaired skin barrier resulting from defects in filaggrin expression has been hypothesized as a gateway for food allergens and as a way to avoid the oral tolerance pathways of the gut mucosa. […] The phenomenon of skin sensitization leading to an oral allergic response has been recently coined the “dual-allergen-exposure” hypothesis. […] Given the difficulty of eliminating food allergy once it is established, primary prevention based on this hypothesis becomes important.

• #19 Food allergy: an updated review on pathogenesis, diagnosis, prevention and management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8023067/

  The respiratory route is also responsible for triggering sensitization: inhaled aeroallergens can cross-react with food antigens, resulting in an oral allergy syndrome. Once sensitization has been established, re-exposure to the antigen can led to local or systemic manifestations. Once produced, IgE bind to its high-affinity receptor FcRI on the surface of mast cells and basophils, therefore arming these cells for activation on re-exposure to the antigen. […] The second contact with the antigen activates and makes these cells degranulate, resulting in performed mediators release (histamine, tryptase, platelet activating factor, prostaglandin and leukotrienes) and can lead to local and systemic manifestations. […] Several hypotheses have been formulated to explain the increase of FA. […] The hygiene hypothesis. A lack of microbes and infections exposure in early childhood might increase susceptibility to allergic disease by altering the development of the immune system through an imbalance of the immune responses in favor of the Th2 lymphocyte profile rather than Th1.

• #20 Food allergy: Mechanisms, diagnosis, and management – Karnataka Paediatric Journal

  https://iap-kpj.org/food-allergy-mechanisms-diagnosis-and-management/

  In genetically predisposed individuals, due to the defective epithelial barrier or weak oral tolerance, the food antigens leak through the gut to facilitate sensitization. On re-exposure of the food antigens, specific IgE antibodies residing on mast cells and basophils in the gut bind to the ingested food allergen. This leads to the release of several mediators and cytokines responsible for the clinical cascade of an allergic reaction. […] A number of non-IgE mediated food hypersensitivity disorders have also been identified. The exact mechanism involved in such disorders is still a matter of debate in certain situations. Non-IgE mediated FA encompasses a wide range of disorders affecting many systems. […] Allergy skin prick test for foods with histamine and saline controls. […] Even though few studies, initially have shown some promising results of bacterial products in preventing atopic dermatitis and augmentation of sustained oral tolerance in food oral immunotherapy (OIT), not all studies have been promising.

• #21 Pathogenesis of allergic diseases and implications for therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-023-01344-4

  Allergic diseases such as allergic rhinitis (AR), allergic asthma (AAS), atopic dermatitis (AD), food allergy (FA), and eczema are systemic diseases caused by an impaired immune system. […] The pathogenesis of allergic diseases is complex and involves many factors, including maternal-fetal environment, living environment, genetics, epigenetics, and the body’s immune status. […] The pathogenesis of allergic diseases exhibits a marked heterogeneity, with phenotype and endotype defining visible features and associated molecular mechanisms, respectively. […] The pathogenesis of FA is an IgE-dependent type I hypersensitivity to a specific food allergen. Its pathological process is divided into two stages: in the allergic sensitization stage, the initial exposure to the allergen results in tolerance breakdown, with subsequent generation of specific IgE, vasoactive substances and allergic response mediators such as histamine and platelet activating factor.

• #22

  https://www.ijbcp.com/index.php/ijbcp/article/view/5263

  An exaggerated immune reaction to a food that takes place in a vulnerable host is referred to as a food allergy. The two main types of food-induced allergy diseases are those caused by Immunoglobulin E (IgE) antibodies and those caused by non-IgE-mediated mechanisms. […] Age, sex, heredity, and geographic location of the patient, as well as vitamin D deficiency and other allergic reactions, are risk factors that might result in life-threatening food allergies. […] The objective of this study was to throw a light on the pathogenesis, diagnostic methods and possible treatment options for food allergy.

• #23 2 Definitions | Finding a Path to Safety in Food Allergy: Assessment of the Global Burden, Causes, Prevention, Management, and Public Policy | The National Academies Press

  https://nap.nationalacademies.org/read/23658/chapter/4

  This report focuses almost exclusively on IgE-mediated food allergy, which has better defined underlying cellular mechanisms and an established link to many prevalent food allergy reactions. […] Immunoglobulin E is an antibody that, if bound to certain cells bearing receptors for IgE, can trigger intense inflammatory reactions in response to the allergen for which the cell-bound IgE has specificity. […] The IgE-mediated reactions observed in patients with food allergy are often grouped into immediate onset reactions and immediate plus late-phase reactions and can include life-threatening anaphylaxis, gastrointestinal hypersensitivity, urticaria, and pollen-associated food allergy syndrome. […] Specific food allergies likely are a result of complex interactions among genes and the environment (including not only factors in the external environment, such as pollen, pollution, and pathogenic microbes, but also effects of the microbes that normally reside in us—the internal environment of the microbiome).

• #24 Pathogenesis of allergic diseases and implications for therapeutic interventions | Signal Transduction and Targeted Therapy

  https://www.nature.com/articles/s41392-023-01344-4

  During the provocation phase, degranulation of effector cells, such as mast cells, induces allergic inflammation, and serotonin or 5-hydroxytryptamine is released in large amounts, resulting in acute gastrointestinal symptoms, including diarrhea. […] After repeated exposure to food allergens, persistent allergic inflammatory reactions occur and tissue mast cells increase, resulting in persistent gastrointestinal reactions. […] The pathogenesis of allergic diseases is complex, involving many factors such as genetics, epigenetics, environmental factors, microecology and the body’s immune function.

• #25 Food allergy: an updated review on pathogenesis, diagnosis, prevention and management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8023067/

  The dual-allergen hypothesis. Several studies conducted in animals and humans suggest that disrupted skin barrier function in infant eczema might cause allergen sensitization through environmental exposure via the skin rather than oral route. […] The Vitamin D hypothesis. Vitamin D has well-recognized immunoregulatory and tolerogenic functions, and its deficiency is considered a possible risk factors for FA development. […] The microbiota hypothesis. The presence of specific bacterial strains as well as dietary substrate and their metabolites, could influence FA development. […] The false alarm hypothesis. Smith et al. very recently proposed a different theory to explain FA increase. The Western diet is high in advanced glycation end-products (AGEs) deriving from cooked meat, oil and cheese, and high concentration of sugar. They suggest AGEs, that are present or formed from the food in our diet and are alarmins, prime innate signaling, leading to development of FA.

• #26

  https://link.springer.com/article/10.1007/s11882-016-0616-7

  Food allergy is defined as an IgE-mediated hypersensitivity response to ingested food with allergic symptoms ranging from urticaria to life-threatening anaphylaxis. Food allergy is thought to develop because of (1) failed induction of tolerance upon initial exposure to food antigen or (2) breakdown of established tolerance to food antigen. […] We highlight emerging data on food allergy treatment and prevention, emphasizing the growing appeal of manipulating the gut microenvironment using probiotics and helminth products to blunt systemic allergic responses to food. […] Using a mouse peanut allergy model, this group demonstrated that sensitization to food allergen is increased in antibiotic-treated mice or mice lacking commensal microflora. Protection from food allergy can be conferred by Clostridia-containing microbiota that induces host production of the cytokine IL-22, restoring intestinal epithelial barrier function, preventing allergic sensitization to food.

• #27 Food allergy: immune mechanisms, diagnosis and immunotherapy

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5123910/

  The immune changes that accompany food allergen immunotherapy are thought to occur as a progression of several elements. […] The mechanisms by which mast cell and basophil responsiveness to degranulation are decreased early during immunotherapy are under investigation. […] Differences between the immune responses associated with desensitization and tolerance are under active investigation. […] The proposed mechanism of dendritic cell (DC) inhibition by regulatory T (Treg) cells is possibly mediated via cytotoxic T lymphocyte antigen 4 (CTLA4) and lymphocyte activation gene 3 (LAG3). […] The roles of follicular T cells, tissue-resident T cells, CD8+ T cells and T cells remain to be determined.

• #28 Mast Cell Activation Syndrome (MCAS)

  https://www.aaaai.org/conditions-treatments/related-conditions/mcas

  Mast cells are allergy cells responsible for immediate allergic reactions. They cause allergic symptoms by releasing products called mediators stored inside them or made by them. In allergic reactions, this release occurs when the allergy antibody IgE, which is present on the mast cell surfaces, binds to proteins that cause allergies, called allergens. This triggering is called activation, and the release of these mediators is called degranulation. […] Certain mutations in mast cells can produce populations of identical mast cells called clones that overproduce and spontaneously release mediators. The spontaneous production of mediators in these clonal mast cell disorders is called primary activation. […] MCAS is a condition in which the patient experiences repeated episodes of the symptoms of anaphylaxis allergic symptoms such as hives, swelling, low blood pressure, difficulty breathing and severe diarrhea. High levels of mast cell mediators are released during those episodes.

• #29 A Review on Mechanism of Histamine Mediated Allergic Reactions: Therapeutic Role, Safety, and Clinical Efficacy of Cetirizine in Modern Allergy and Other Diseases Management – Biomedical and Pharmacology Journal

  https://biomedpharmajournal.org/vol18no1/a-review-on-mechanism-of-histamine-mediated-allergic-reactions-therapeutic-role-safety-and-clinical-efficacy-of-cetirizine-in-modern-allergy-and-other-diseases-management/

  Histamine-mediated allergic reactions are central to the pathogenesis of various allergic disorders, involving complex molecular mechanisms. […] Allergy development is a multifactorial process that begins during sensitization when particular allergens cause the formation of IgE antibodies. These IgE antibodies cause degranulation, which releases a number of mediators, including histamine, by binding to the high-affinity receptors (FcRI) found on mast cells, basophils, and antigen-presenting cells (APCs). […] Histamine release is a crucial phase in allergic responses, occurring when intracellular histamine stored in mast cell granules is released into the extracellular environment. This is initiated by antigen-antibody interactions, where FcRI-bound IgE on mast cells stimulates tyrosine-protein kinase activation.

• #30 A Review on Mechanism of Histamine Mediated Allergic Reactions: Therapeutic Role, Safety, and Clinical Efficacy of Cetirizine in Modern Allergy and Other Diseases Management – Biomedical and Pharmacology Journal

  https://biomedpharmajournal.org/vol18no1/a-review-on-mechanism-of-histamine-mediated-allergic-reactions-therapeutic-role-safety-and-clinical-efficacy-of-cetirizine-in-modern-allergy-and-other-diseases-management/

  Histamine, synthesized from histidine by the enzyme L-histidine decarboxylase, acts as a potent signaling molecule by binding to H1, H2, H3, and H4 receptors, all belong to the GPCR family. […] Upon binding to the H1 receptor, histamine triggers a cascade involving Gq/11 protein activation and phospholipase C signaling, producing DAG and IP3. This promotes smooth muscle contraction, increases vascular permeability, as well as contributes to the hallmark symptoms of allergic responses, such as itchiness, bronchoconstriction, and tissue swelling. […] Histamine release is one of the primary consequences of mast cell activation, which causes an immediate allergic reaction. […] The mechanism by which mast cells release histamine in response to an antigen-antibody reaction. […] Histamine is produced and released by various human cells, including lymphocytes, enterochromaffin cells, basophils, mast cells, platelets, and histaminergic neurons.

• #31 The immunopathogenesis of cow’s milk protein allergy (CMPA) | Italian Journal of Pediatrics | Full Text

  https://ijponline.biomedcentral.com/articles/10.1186/1824-7288-38-35

  A dysfunction on Treg cellular activity seems to be a necessary background for the spread of both reactions (IgE- and not-IgE mediated CMPA), as the induction of mucosal tolerance in children is linked with an increase of Treg lymphocytes. […] In conclusion, it seems that T lymphocytes subsets play a key role in allergic reactions to cows milk proteins, above all in those not-IgE mediated, and Treg cells are at the basis of oral tolerance to food allergy, so that an altered pattern of the immune system leads to all those atopic reactions, that are not explained by an IgE background.

• #32 The Etiology of IgE-Mediated Food Allergy: Potential Therapeutics and Challenges

  https://www.mdpi.com/1422-0067/26/4/1563

  Immunoglobulin E (IgE)-mediated food allergy has been dramatically increasing in incidence over the last few decades. The combinations of both genetic and environmental factors that affect the microbiome and immune system have demonstrated significant roles in its pathogenesis. […] The morbidity, and at times mortality, that occurs as the result of this specific, reproducible, but impaired immune response is due to the nature of the shift from a regulatory T (Treg) cellular response to a T helper 2 (Th2) cellular response. This imbalance caused by food allergens results in an interleukin (IL)-4 and IL-13 dominant environment that drives B cell activation and differentiation into IgE-producing plasma cells. […] Current therapeutic strategies involve avoidance and broad symptom management upon accidental exposure; however, no definitive cure exists.

• #33 Food Allergies: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/135959-overview

  Eosinophilic esophagitis and gastrointestinal disease are eosinophilic mediated. Eosinophil granules release substances toxic to multiple tissues. These substances include major basic protein 1 and 2, eosinophilic cationic protein, eosinophilic-derived neurotoxin, and eosinophil peroxidase. Triggering of eosinophils leads to the generation of proinflammatory cytokines including Il-1, Il-3, Il-4, Il-5, and Il-13, and granulocyte-macrophage colony-stimulating factor. Eosinophil degranulation is responsible for tissue damage in eosinophilic gut disease.

• #34 Primary navigation

  https://cfpub.epa.gov/ncer_abstracts/index.cfm/fuseaction/display.abstractDetail/abstract_id/8939/report/0

  Food allergy is a major public health problem affecting 6-8% of children in the United States, but there is a dearth of information on pathogenesis or preventative strategies. […] The proposed studies aim to assess mechanisms of food allergy pathogenesis and identify potential triggers of allergic sensitization. […] Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine that has a central role in the development of allergic inflammation in the skin and lung. In the gastrointestinal tract TSLP has a regulatory function, however we hypothesize that an over-expression of TSLP may promote allergic sensitization to food allergens. […] To test the role of TSLP in food allergy, its mechanism of action, and its regulation in the gastrointestinal tract. […] We hypothesize that epithelial cell-derived TSLP conditions gastrointestinal dendritic cells to generate Th2-skewed CD4+ T cells that orchestrate the development of food allergy.

• #35 Food Allergy: Our Evolving Understanding of Its Pathogenesis, Prevention, and Treatment. 2015 – OIT 101BloglovinDribbbleEmailFacebook

  https://www.oit101.org/research/food-allergy-evolving-understanding-pathogenesis-prevention-treatment-2015/

  Food allergy is defined as an IgE-mediated hypersensitivity response to ingested food with allergic symptoms ranging from urticaria to life-threatening anaphylaxis. Food allergy is thought to develop because of (1) failed induction of tolerance upon initial exposure to food antigen or (2) breakdown of established tolerance to food antigen. […] We review current understanding of the pathogenesis, epidemiology, and natural history of food allergy, including the unconventional IgE-mediated food allergy to mammalian meat known as alpha-gal food allergy. […] We highlight emerging data on food allergy treatment and prevention, emphasizing the growing appeal of manipulating the gut microenvironment using probiotics and helminth products to blunt systemic allergic responses to food.

• #36 Primary navigation

  https://cfpub.epa.gov/ncer_abstracts/index.cfm/fuseaction/display.abstractDetail/abstract_id/8939/report/0

  Understanding what triggers up-regulate TSLP expression could be important for identifying environmental or dietary triggers that promote food allergy. […] We hypothesize that this transgenic mouse will be susceptible to the development of food allergy, and in addition to providing evidence for a central role of TSLP in food allergy, it would provide a novel murine model of spontaneous food allergy for testing either the allergenicity of food proteins or the efficacy of novel therapeutics. […] The results from the first aim will define mechanisms of experimental food allergy, that is necessary for the design of novel targeted therapeutics. […] The second aim will identify potentially avoidable triggers of food allergy that could be used in public health approaches for food allergy avoidance. […] The third aim will provide a novel in vivo model for testing the allergenicity of food proteins.

• #37

  https://www.jci.org/

  Complements involvement in allergic Th2 immunity: a cross-barrier perspective […] Type 2 (Th2) allergic diseases are chronic conditions characterized by a Th2-polarized immune response to allergens. These diseases can be categorized by affected barrier sites: skin (atopic dermatitis, allergic contact dermatitis), gut (food allergy), and respiratory tract (e.g., asthma, chronic rhinosinusitis). The global prevalence of Th2 allergic diseases has increased the need for a deeper understanding of their pathophysiology. Several associations have been identified between genetic variants in the genes encoding components of the complement system and allergic disease. Moreover, levels of several complement proteins are elevated in patients with allergy. Experimental evidence demonstrates that the complement system plays a critical role in the development of these diseases across barrier sites. While site-specific differences exist in the complement components involved, key pathways, particularly C3 and C5, are prominent across the skin, gut, and lung.

• #38 The Rockefeller University » New clues to the mechanism behind food tolerance and allergies

  https://www.rockefeller.edu/news/37240-new-clues-to-the-mechanism-behind-food-tolerance-and-allergies/

  New clues to the mechanism behind food tolerance and allergies […] Now, new research identifies specific gut cell types that communicate with T cellsprompting them to tolerate, attack, or simply ignoreand explains how these opposing responses are triggered. […] The findings, published in Science, give scientists a new understanding of how the intestinal immune system keeps the gut in balance, and may ultimately shed light on the root causes and mechanisms of food allergies and intestinal diseases. […] The intestinal immune system is complicated machinery. Tolerance to food begins with antigen presenting cells, or APCs, instructing T cells to stand down. […] After optimizing LIPSTIC for the task, Canesso and colleagues succeeded in pinpointing those APCs that promote tolerancea process primarily handled by two types: cDC1s and Rort+ APCs.

• #39 The Rockefeller University » New clues to the mechanism behind food tolerance and allergies

  https://www.rockefeller.edu/news/37240-new-clues-to-the-mechanism-behind-food-tolerance-and-allergies/

  They also uncovered how infections of the intestines can cause interference, demonstrating in mice that the parasitic worm Strongyloides venezuelensis shifts the balance away from tolerance promoting APCs and toward those that promote inflammation. […] Finally, the team characterized the molecular signals underpinning these immune shifts, identifying key cytokines and pathways that influence how APCs present antigens and modulate immune responses. […] Together, the findings illuminate how the immune system maintains food tolerance and, in the case of parasitic infections, highlights the specific immune mechanisms that can go awry. […] While these findings arent directly relevant to food allergies, they do lay some groundwork for further investigation into food intolerance.

• #40 Food Allergy – Immunology; Allergic Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/immunology-allergic-disorders/allergic-autoimmune-and-other-hypersensitivity-disorders/food-allergy

  Symptoms and signs of food allergies vary by allergen, mechanism, and patient age. […] T-cell-mediated reactions tend to involve the GI tract, causing symptoms such as subacute or chronic abdominal pain, nausea, cramping, and diarrhea. […] Food elimination is a primary treatment for food allergies. […] Oral cromolyn appears to effectively lessen the allergic reaction to food. […] Long-term corticosteroid treatment is useful for symptomatic eosinophilic enteropathy. […] Omalizumab may be used to help prevent severe IgE mediated allergic reactions to foods. […] Oral immunotherapy for desensitization to peanuts uses defatted peanut allergen powder. […] Sublingual immunotherapy for IgE-mediated food allergies involves placing drops of glycerinated allergen extracts under the tongue once a day.

• #41 Reddit – The heart of the internet

  https://www.reddit.com/r/FoodAllergies/comments/uyzx2v/food_allergy_news_gene_mechanism_behind_remission/

  Researchers Find Gene Mechanism Behind Peanut Allergy Remission with Potential for Other Allergies. Super exciting research from Australia has determined the underlying mechanism behind remission in people with peanut allergies after treatment, a finding that could lead to more targeted treatments for food allergies across the board that result in remission vs desensitization. […] Basophil Activation Tests which promise significantly more precise allergy testing than today’s skin prick and blood tests were introduced a decade ago. But isolating the basophils is so cumbersome that the tests are used primarily for research. Now, this exciting new technology promises to make the testing widespread.

• #42 Food Allergy – Immunology; Allergic Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/immunology-allergic-disorders/allergic-autoimmune-and-other-hypersensitivity-disorders/food-allergy

  Diagnosis of oral allergy syndrome is usually made clinically but can be confirmed by skin prick testing. […] Treatment of oral allergy syndrome involves avoiding the food, thoroughly cooking the food to denature the protein, and carrying a prefilled, self-injecting epinephrine syringe in case of an anaphylactic reaction. […] Eosinophilic gastroenteropathy causes pain, cramps, and diarrhea with blood eosinophilia, eosinophilic infiltrates in the gut, and protein-losing enteropathy; patients have a history of atopic disorders. […] Alpha-gal syndrome refers to a recently discovered form of allergy to red meat. […] Evidence suggests that the bite (particularly multiple bites) from such ticks may sensitize a person to alpha-gal. […] The allergic reactions can include an itchy rash, indigestion, constipation, nausea, and anaphylactic reactions.

• #43 Food allergy: Mechanisms, diagnosis, and management – Karnataka Paediatric Journal

  https://iap-kpj.org/food-allergy-mechanisms-diagnosis-and-management/

  There has been promising evidence on adjuvant of omalizumab with multiple food allergen OIT and has been shown to reduced time (about 67 weeks) taken for developing tolerance to these foods in Phase 1 of these trials, saving them about 67 weeks worth of time if they had undergone desensitization to individual foods. […] In conclusion, as we are encountering increased prevalence of FA as a part of Allergic March, time has come to build on available knowledge and to set up new studies which can provide us more armor in the near future.

• #44 Peanut Oral Immunotherapy Efficacious in Adults with Allergy – Dermatology Advisor

  https://www.dermatologyadvisor.com/news/peanut-oral-immunotherapy-efficacious-in-adults-with-allergy/

  Peanut oral immunotherapy (OIT) is efficacious for adults with peanut allergy, according to a study published online April 23 in Allergy. […] Peanut OIT can be an efficacious treatment for desensitization of adult peanut allergic patients, the authors write.

• #45 Mast Cell Activation Syndrome (MCAS)

  https://www.aaaai.org/conditions-treatments/related-conditions/mcas

  Mast cell mediators increase during the episode. Those mediators should be measured during acute episodes and at baseline looking for elevations during symptoms. […] The immediate goal is to provide relief for the patient. Lack of response to these treatments suggests that MCAS is not present. […] Omalizumab (which blocks binding of IgE to its receptors) has been reported to reduce mast cell reactivity and sensitivity to activation which can reduce anaphylactic episodes. […] These criteria require the presence of anaphylactic symptoms, the elevation of mast cell mediators during symptoms and the resolution of symptoms with appropriate treatment(s).

• #46 Food Allergy – Immunology; Allergic Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/immunology-allergic-disorders/allergic-autoimmune-and-other-hypersensitivity-disorders/food-allergy

  Omalizumab (a humanized recombinant monoclonal anti-IgE antibody) and other anti-IgE monoclonal antibodies have been used to treat people who have had severe anaphylactic reactions to food. […] Food allergy is commonly mediated by IgE (typically resulting in acute systemic allergic reactions) or T cells (typically resulting in chronic gastrointestinal symptoms).

• #47 The Etiology of IgE-Mediated Food Allergy: Potential Therapeutics and Challenges

  https://www.mdpi.com/1422-0067/26/4/1563

  This narrative review highlights how the elucidation of the pathogenesis of IgE-mediated food allergy resulted in the development of therapeutics that are more specific to these individual receptors and molecules which have been relatively successful in mitigating this potentially life-threatening allergic response. […] Therefore, given the understanding of their mechanism of action and the overlap with the mechanism of IgE-mediated food allergies, probiotics and small molecule natural compounds may provide novel therapeutic and preventative strategies.

• #48

  https://www.mattioli1885journals.com/index.php/actabiomedica/article/view/10316

  Food allergy (FA) is an adverse immunologic response triggered by normally innocuous food protein antigens. FA can be broadly classified into those that are IgE mediated, those that are mediated by both IgE-dependent and IgE-independent pathways (mixed), and those that are not IgE mediated Immunoglobulin E. (IgE)-mediated reaction is characterized by rapid onset of symptoms involving respiratory, gastrointestinal, dermatologic and cardiovascular systems; mixed and non-IgE-mediated has a longer onset and manifests primary in the gastrointestinal tract and skin. […] Recent studies emphasize the possibility of preventing FA through early introduction of food (peanuts and egg) to high-risk infants. […] Currently under study are recently developed treatment approaches for FA management including specific OIT.

• #49 Eating avocados during pregnancy associated with lower food allergy risk in baby | EurekAlert!

  https://www.eurekalert.org/news-releases/1082890

  An observational study among 2,272 mother-child pairs in Finland found that infants had 44% lower odds of developing food allergies at 12 months if their mother consumed fresh avocado during pregnancy, after adjusting for other lifestyle, delivery, and maternal health factors. […] This is the first published study to link avocados in the maternal diet to a lower risk of infant food allergies. […] Findings from this study cannot establish causation or be applied to all audiences, and while more research is needed to understand the exact mechanism, they underscore the value of avocados.

• #50 Natural course of IgE-mediated food allergy in children

  https://www.e-cep.org/journal/view.php?doi=10.3345/cep.2022.01004

  The prevalence of food allergy and food-induced anaphylaxis in children is increasing worldwide. […] Although our understanding of the mechanism underlying the resolution of food allergy is incomplete, the roles of dendritic cells, regulatory T cells, and regulatory B cells are important. […] Dendritic, regulatory T, and regulatory B cells significantly contribute to the natural course of food allergy. […] The potential factors affecting the natural course of food allergy are age at diagnosis, symptom severity, sensitization status and its change rate, and external factors such as diet and interventions. […] Tolerance to food allergens is driven mainly by antigen-presenting cells within the gut lamina propria by the promotion of T-cell differentiation. […] Regulatory T cells, especially Foxp3+ regulatory T cells characterized by CD25 expression, play an essential role in oral tolerance.

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