scholarly journals Oral Immunotherapy and Basophil and Mast Cell Reactivity in Food Allergy

2020 ◽  
Vol 11 ◽  
Author(s):  
Anuya Paranjape ◽  
Mindy Tsai ◽  
Kaori Mukai ◽  
Ramona A. Hoh ◽  
Shilpa A. Joshi ◽  
...  

Basophil activation tests (BATs) can closely monitor, in vitro, a patient’s propensity to develop type I hypersensitivity reactions. Because of their high specificity and sensitivity, BATs have become promising diagnostic tools, especially in cases with equivocal clinical histories, skin prick test results, and/or levels of specific IgE to allergen extracts. BATs also are useful as tools for monitoring the effects of treatment, since oral immunotherapy (OIT) studies report a diminution in patients’ basophil responsiveness over the course of OIT. This review will discuss the BAT findings obtained before, during, and after OIT for food allergy. We will mainly focus on the association of basophil responsiveness, and alterations in basophil surface markers, with clinical outcomes and other clinical features, such as blood levels of specific IgG and IgE antibodies. The detailed analysis of these correlations will ultimately facilitate the use of BATs, along with other blood biomarkers, to differentiate short-term desensitization versus sustained unresponsiveness and to improve treatment protocols. Given the critical anatomic location of mast cells adjacent to the many IgE+ plasma cells found in the gastrointestinal tissues of allergic individuals, we will also discuss the role of gastrointestinal mast cells in manifestations of food allergies.

2016 ◽  
Vol 4 (1) ◽  
pp. 1 ◽  
Author(s):  
Sidonie Lavergne

Drug hypersensitivity reactions (DHR) are immune-mediated idiosyncratic adverse drug events. Type I DHR are often referred to as “immediate” and involve B lymphocyte-secreted IgE that bind to the membrane of basophils and mast cells, inducing their degranulation. This review presents various in vitro tests that were developed in the field of human type I HS and implemented as clinical diagnostic tools in human cases of immediate DHR. The respective strengths and weaknesses of each test will be discussed in parallel of validation data such as specificity and sensitivity whenever available. Some of them have also been used as diagnostic tools in veterinary medicine, but not in cases of immediate DHR. Most of these diagnostic tools can be categorized into humoral and cellular tests. The former tests measure serum concentrations of factors, such as histamine, tryptase, and drug-specific IgE. The latter assays quantify markers of drug-induced basophil activation or drug-specific lymphocyte proliferation. Pharmacogenetic markers have also been investigated in immediate DHR, but not as extensively as in non-immediate ones. Throughout, practical aspects and limitations of the tests, as well as sensitivity and specificity parameters, will be presented. In addition, the experience of veterinary medicine with these diagnostic tools will be summarized. However, to date, none of them has ever been reported in a veterinary case of type I DHR.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1586
Author(s):  
Tomoe Yashiro ◽  
Hanako Ogata ◽  
Syed Faisal Zaidi ◽  
Jaemin Lee ◽  
Shusaku Hayashi ◽  
...  

Recently, the involvement of the nervous system in the pathology of allergic diseases has attracted increasing interest. However, the precise pathophysiological role of enteric neurons in food allergies has not been elucidated. We report the presence of functional high-affinity IgE receptors (FcεRIs) in enteric neurons. FcεRI immunoreactivities were observed in approximately 70% of cholinergic myenteric neurons from choline acetyltransferase-eGFP mice. Furthermore, stimulation by IgE-antigen elevated intracellular Ca2+ concentration in isolated myenteric neurons from normal mice, suggesting that FcεRIs are capable of activating myenteric neurons. Additionally, the morphological investigation revealed that the majority of mucosal mast cells were in close proximity to enteric nerve fibers in the colonic mucosa of food allergy mice. Next, using a newly developed coculture system of isolated myenteric neurons and mucosal-type bone-marrow-derived mast cells (mBMMCs) with a calcium imaging system, we demonstrated that the stimulation of isolated myenteric neurons by veratridine caused the activation of mBMMCs, which was suppressed by the adenosine A3 receptor antagonist MRE 3008F20. Moreover, the expression of the adenosine A3 receptor gene was detected in mBMMCs. Therefore, in conclusion, it is suggested that, through interaction with mucosal mast cells, IgE-antigen-activated myenteric neurons play a pathological role in further exacerbating the pathology of food allergy.


Children ◽  
2021 ◽  
Vol 8 (6) ◽  
pp. 497
Author(s):  
Aikaterini Anagnostou

Background: Food allergies are common, affecting 1 in 13 school children in the United States and their prevalence is increasing. Many misconceptions exist with regards to food allergy prevention, diagnosis and management. Objective: The main objective of this review is to address misconceptions with regards to food allergies and discuss the optimal, evidence-based approach for patients who carry this diagnosis. Observations: Common misconceptions in terms of food allergy prevention include beliefs that breastfeeding and delayed introduction of allergenic foods prevent the development of food allergies. In terms of diagnosis, statements such as ‘larger skin prick tests or/and higher levels of food-specific IgE can predict the severity of food-induced allergic reactions’, or ‘Tryptase is always elevated in food-induced anaphylaxis’ are inaccurate. Additionally, egg allergy is not a contraindication for receiving the influenza vaccine, food-allergy related fatalities are rare and peanut oral immunotherapy, despite reported benefits, is not a cure for food allergies. Finally, not all infants with eczema will develop food allergies and epinephrine auto-injectors may unfortunately be both unavailable and underused in food-triggered anaphylaxis. Conclusions and relevance: Healthcare professionals must be familiar with recent evidence in the food allergy field and avoid common misunderstandings that may negatively affect prevention, diagnosis and management of this chronic disease.


2020 ◽  
Vol 21 (4) ◽  
pp. 1498 ◽  
Author(s):  
David O. Lyons ◽  
Nicholas A. Pullen

Mast cells are often regarded through the lens of IgE-dependent reactions as a cell specialized only for anti-parasitic and type I hypersensitive responses. However, recently many researchers have begun to appreciate the expansive repertoire of stimuli that mast cells can respond to. After the characterization of the interleukin (IL)-33/suppression of tumorigenicity 2 (ST2) axis of mast cell activation—a pathway that is independent of the adaptive immune system—researchers are revisiting other stimuli to induce mast cell activation and/or subsequent degranulation independent of IgE. This discovery also underscores that mast cells act as important mediators in maintaining body wide homeostasis, especially through barrier defense, and can thus be the source of disease as well. Particularly in the gut, inflammatory bowel diseases (Crohn’s disease, ulcerative colitis, etc.) are characterized with enhanced mast cell activity in the context of autoimmune disease. Mast cells show phenotypic differences based on tissue residency, which could manifest as different receptor expression profiles, allowing for unique mast cell responses (both IgE and non-IgE mediated) across varying tissues as well. This variety in receptor expression suggests mast cells respond differently, such as in the gut where immunosuppressive IL-10 stimulates the development of food allergy or in the lungs where transforming growth factor-β1 (TGF-β1) can enhance mast cell IL-6 production. Such differences in receptor expression illustrate the truly diverse effector capabilities of mast cells, and careful consideration must be given toward the phenotype of mast cells observed in vitro. Given mast cells’ ubiquitous tissue presence and their capability to respond to a broad spectrum of non-IgE stimuli, it is expected that mast cells may also contribute to the progression of autoimmune disorders and other disease states such as metastatic cancer through promoting chronic inflammation in the local tissue microenvironment and ultimately polarizing toward a unique Th17 immune response. Furthermore, these interconnected, atypical activation pathways may crosstalk with IgE-mediated signaling differently across disorders such as parasitism, food allergies, and autoimmune disorders of the gut. In this review, we summarize recent research into familiar and novel pathways of mast cells activation and draw connections to clinical human disease.


2005 ◽  
Vol 201 (6) ◽  
pp. 859-870 ◽  
Author(s):  
Junko Sasaki ◽  
Takehiko Sasaki ◽  
Masakazu Yamazaki ◽  
Kunie Matsuoka ◽  
Choji Taya ◽  
...  

The membrane phospholipid phosphatidylinositol 4, 5-bisphosphate [PI(4,5)P2] is a critical signal transducer in eukaryotic cells. However, the physiological roles of the type I phosphatidylinositol phosphate kinases (PIPKIs) that synthesize PI(4,5)P2 are largely unknown. Here, we show that the α isozyme of PIPKI (PIPKIα) negatively regulates mast cell functions and anaphylactic responses. In vitro, PIPKIα-deficient mast cells exhibited increased degranulation and cytokine production after Fcε receptor-I cross-linking. In vivo, PIPKIα−/− mice displayed enhanced passive cutaneous and systemic anaphylaxis. Filamentous actin was diminished in PIPKIα−/− mast cells, and enhanced degranulation observed in the absence of PIPKIα was also seen in wild-type mast cells treated with latrunculin, a pharmacological inhibitor of actin polymerization. Moreover, the association of FcεRI with lipid rafts and FcεRI-mediated activation of signaling proteins was augmented in PIPKIα−/− mast cells. Thus, PIPKIα is a negative regulator of FcεRI-mediated cellular responses and anaphylaxis, which functions by controlling the actin cytoskeleton and dynamics of FcεRI signaling. Our results indicate that the different PIPKI isoforms might be functionally specialized.


1996 ◽  
Vol 115 (4) ◽  
pp. 312-318 ◽  
Author(s):  
Jacquelynne P. Corey ◽  
Anil Gungor

The role of immunoglobulin E-mediated food allergy in subjects with allergic disorders, especially in patients with rhinitis and sinusitis, is underestimated by clinicians because of the initial attribution of these disorders to immediate-type hypersensitivity reactions. The difficulties of diagnosing food-related reactions have caused further delay in their recognition and incorporation into the daily practice of diagnosing food allergy. Two of the diagnostic methods for food allergy are the in vitro assay of total immunoglobulin E and the measurement of food-specific immunoglobulin E levels in serum with the radioallergosorbent test. Measurement of specific immunoglobulin E level is the most commonly used but also one of the most controversial techniques. We examined 123 patients with rhinitis who were referred to our otolaryngology/allergy clinic between January and April 1995. All patients received an initial radioallergosorbent test screen, which included milk. We determined the positive predictive value of this positive screen and, in particular, of a positive test for milk in the diagnosis of immunoglobulin E-mediated food allergies in these patients. Conclusions were based on comparison with the result of an additional radioallergosorbent test food panel consisting of eight common and two investigational food allergens. (Otolaryngol Head Neck Surg 1996;115:312-8.)


2021 ◽  
Vol 11 (5) ◽  
pp. 213-220
Author(s):  
Vaishali H. Shinde ◽  
Ramesh Bawaskar ◽  
K.C. Muraleedharan

Abstract Allergy, formally called type I (or immediate) hypersensitivity  is one of four or more forms of hypersensitivity manifesting in various forms like, Atopic eczema, Allergic urticaria, Allergic rhinitis, Allergic asthma, , Food allergy,  etc.  The growing incidence of Food allergy needs attention since its burden is mainly on children and adolescents. Various factors has been attributed to the growing incidence of food allergy such as food habits, cooking habits, cultural differences, various developmental parameters and exchange of food products. The World Allergy Organization has estimated 220 to 550 million people suffering from food allergy with a large chunk of population from the developed countries. No concrete data is available on status of food allergy in India though some sporadic research has been published. In spite of diligent research worldwide, an effective mechanism to cure this condition has not been evolved till today. Since effectiveness of homeopathy has been proved in various allergy conditions, the modality of using the same has been explored in this article.   Key words: Food allergy, Homoeopathy, Type I hypersensitivity 


2003 ◽  
Vol 56 (1-2) ◽  
pp. 54-57 ◽  
Author(s):  
Jelena Tomic ◽  
Mirjana Jovanovic ◽  
Dusan Tomic

Introduction Food allergy is a form of adverse food reaction to different nutritive agents caused by immunological mechanisms. This condition is frequent in individuals with genetic predisposition. Frequency of food allergies in childhood varies in general population from 0.3 - 7.5 %. Characteristics of neonatal and infant gastrointestinal tracts are described as well as the role of gastrointestinal tract?s immunological immaturity in development of food sensitivity. Pathogenesis Features of physical and immunological barriers of gastrointestinal tract are described as well as their role in physiological conditions, in digestion and absorption of foreign proteins and prevention of foreign agents penetration and potentially dangerous proteins into the systemic circulation. Gastrointestinal-associated lymphoid tissue (GALT) is the basic part of immunological barrier. Its first role is to induce oral tolerance. In normal conditions cytokines induce T cells towards Th2 response and also promote synthesis of IgA antibodies Pathogenic mechanisms in evolution of reaginic hypersensibility in cases of chronic inflammation are also described. Pathological status of gamma/delta T cells plays an important role in this process, resulting in loss of oral tolerance and development of sensibilitivity. Conclusion Diagnostic procedures are multiple and complex. They consist of detailed history taking clinical findings, in vitro and in vivo tests, endoscopy, elimination diets and oral provocation tests. Food allergy in childhood is often transient and resolves spontaneously.


2021 ◽  
Vol 42 (2) ◽  
pp. 118-123
Author(s):  
Aikaterini Anagnostou

Food allergies are common and affect 6‐8% of children in the United States; they pose a significant burden on the quality of life of children with allergy and their caregivers due to multiple daily restrictions. Despite the recommended dietary avoidance, reactions tend to occur due to unintentional exposure to the allergenic food trigger. Fear of accidental ingestions with potentially severe reactions, including anaphylaxis and death, creates anxiety in individuals with food allergy. Oral immunotherapy has emerged as a form of active and potentially disease-modifying treatment for common food allergies encountered in childhood. The efficacy of oral immunotherapy is high, with the majority of participants achieving desensitization and, as a result, protection from trace exposures and improved quality of life. The main risk of oral immunotherapy consists of allergic reactions to treatment. In general, rates of allergic reactions and anaphylaxis are reported to be higher in individuals pursuing therapy options, but most subjects who undergo oral immunotherapy will likely experience mild or moderate reactions during treatment. Adverse events tend to reduce in both frequency and number in the maintenance period. The use of immune modulators alongside oral immunotherapy has been suggested, with the aim to improve efficacy and safety, and to facilitate the overall process. It is evident that the landscape of food allergy management is changing and that the future looks brighter, with different options emerging over time. The process of how to choose the appropriate option becomes a discussion between the clinician and the patient, which involves a joint review of the current medical evidence but also the patient's preference for balancing particular attributes of the treatment. By working together, providers and patients will ensure achievement of the best possible outcome for children with food allergies.


Author(s):  
Yoshihiro Takasato ◽  
Yosuke Kurashima ◽  
Masahiro Kiuchi ◽  
Kiyoshi Hirahara ◽  
Sayuri Murasaki ◽  
...  

AbstractOral immunotherapy (OIT) is an effective approach to controlling food allergy. Although the detailed molecular and cellular mechanisms of OIT are unknown currently, they must be understood to advance the treatment of allergic diseases in general. To elucidate the mechanisms of OIT, especially during the immunological transition from desensitization to allergy regulation, we generated a clinical OIT murine model and used it to examine immunological events of OIT. We found that in mice that completed OIT successfully, desensitized mast cells (MCs) showed functionally beneficial alterations, such as increased induction of regulatory cytokines and enhanced expansion of regulatory T cells. Importantly, these regulatory-T-cell-mediated inhibitions of allergic responses were dramatically decreased in mice lacking OIT-induced desensitized MC. Collectively, these findings show that the desensitization process modulates the activation of MCs, leading directly to enhanced induction of regulatory-T-cell expansion and promotion of clinical allergic unresponsiveness. Our results suggest that efficiently inducing regulatory MCs is a novel strategy for the treatment of allergic disease.


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