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Basophil responsiveness in OIT treatment outcome groups (i.e., Success vs Failure) is significantly different at all times tested. Basophil responsiveness to peanut extract (%CD63high PE AUC) evaluated at multiple time points during OIT. Subjects were divided into two groups based on whether they did (Success) or did not (Failure) develop sustained unresponsiveness assessed by an oral food challenge at week 117. (A) Peanut 0 – the treatment arm in which subjects completely avoided peanut consumption after the end of desensitization phase (Week 104). (B) Peanut 300 – the treatment arm that maintained subjects at a low dose (i.e., 300 mg/day) of peanut consumption, from week 104 onwards. Whiskers represent the range (minimum to maximum values of AUC), boxes extend from 25th to 75th percentiles. The lines in the middle of the boxes are medians. Individual values are shown as circles. P values were determined by Mann-Whitney test. These are from Figures 4A, B of Tsai and Mukai et al. (51).
Source publication
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...
Citations
... SLIT is a sublingual delivery method for allergenic proteins from food, which is less effective than oral immunotherapy (OIT) in building long-term tolerance [50]. However, it is safer than OIT in terms of safety. ...
Food allergy (FA) has significantly increased in the last decade, and its diagnosis is a continuous challenge. Mild cases are often neglected or detected late, and in children, parents may not be able to accurately interpret symptoms. It is crucial to differentiate FAs from food intolerance and toxic reactions. To provide personalized management, accurate diagnosis is essential. Modern diagnostic tests, such as component diagnosis and epitope reactivity, allow for a more accurate therapeutic approach and reliable prognosis evaluation. Investigations like serum IgE, elimination diets, oral food challenges, single, blind, and double-blind tests, and skin tests are used. Anaphylaxis risk can be assessed using molecular diagnostics/component-resolved diagnosis (CRD) and a basophilic activation test (BAT). These tests allow for planned, individualized therapy based on molecular and clinical characteristics. Understanding immunological processes, diagnostics, and immunotherapies in FAs is crucial for evaluating food allergen exposure, detecting allergic responses, analyzing clinical manifestations, highlighting diagnostic options, and demonstrating appropriate therapeutic strategies. Key words: Food allergy, paediatric, basophilic activation test, component-resolved diagnosis
... The continuous allergenic stimulation of basophils and MCs through the administration of higher doses of food allergen in oral immunotherapy (OIT) reduce cell degranulation and release of preformed mediators. Such effect prevents the development of the allergic reaction to unintentional contact with the allergen and the consequent onset of multiorgan symptoms [43]. However, this treatment is not free from risks and has some limitations. ...
Asthma, chronic urticaria, and atopic dermatitis are some of the most numerous allergic diseases affecting children. Recent advances in the understanding of their specific intracellular molecular pathways have led to the approval of monoclonal antibodies targeting definite inflammatory molecules in order to control symptoms and improve quality of life. Less is known about other allergic and immunologic disorders such as rhinosinusitis with nasal polyps, eosinophilic esophagitis, anaphylaxis, and food allergy undergoing allergen immunotherapy. The increasing evidence of the molecular mechanisms underlying their pathogeneses made it possible to find in children new indications for known biological drugs, such as omalizumab and dupilumab, and to develop other ones even more specific. Promising results were recently obtained, although few are currently approved in the pediatric population. In this review, we aim to provide the latest evidence about the role, safety, and efficacy of biologic agents to treat allergic and immunologic diseases in children.
... Basophils share many mediators and receptors with MC [24] and are more commonly used to perform laboratory allergen-specific activation tests (BAT), since they are easy to sample from whole blood. BAT has been demonstrated useful to confirm IgE-mediated allergy and also to monitor allergen immunotherapy, in order to differentiate short-term desensitization versus sustained unresponsiveness to the allergen [25,26]. ...
Purpose of Review
The purpose of this review is to provide a better understanding of anaphylaxis pathophysiology and describe the underlying mechanisms, effector cells, and the potential biomarkers involved depending on the anaphylaxis endotypes.
Recent Findings
New insight into the potential relevance of pathways others than IgE-dependent anaphylaxis has been unraveled, as well as other biomarkers than tryptase, such as the role of platelet activation factor, basogranulin, dipeptidyl peptidase I, CCL-2, and other cytokines.
Summary
Gaining knowledge of all the mediators and cellular activation/communication pathways involved in each endotype of anaphylaxis will allow the application of precision medicine in patients with anaphylactic reactions, providing insights to the most appropriate approach in each case and helping to stratify severity and risk prediction.
... SLIT consists of the sublingual administration of liquid preparations containing proteins from food that is allergenic. It is less effective than the OIT, especially in achieving a long-lasting tolerance because the maximum amount of allergen that can be administered by this method is a few milligrams [60,61]. In terms of its safety profile, this therapy was found to be superior to the OIT. ...
... Omalizumab is an anti-IgE monoclonal antibody. It works by binding to the Fc region of IgE antibodies, blocking the binding to specific receptors on mast cells and basophils [59,60,68], preventing their degranulation and therefore the appearance of allergic manifestations. Omalizumab should be initiated before the OIT and continued for a few more weeks in parallel [31,69,70]. ...
Food allergy (FA) is a condition with a growing incidence and is a constant concern for the medical world and healthcare providers. With potential symptoms including anaphylaxis, in the event of an allergic reaction the patient's life may well be endangered. The diagnosis of FA is a continuous challenge because mild cases tend to be ignored or diagnosed late and young children with allergies are cared for by parents, who are not always able to accurately interpret symptoms. It is very important to be able to differentiate FAs from food intolerance and toxic reactions to food. An accurate diagnosis is required to provide personalized management of an FA. More sophisticated and accurate diagnostic tests, including component diagnosis and epitope reactivity, allow the provision of a directed diagnosis, a more accurate therapeutic approach, and a useful prognostic evaluation. Tests used in current practice include the specific search for serum IgE, elimination diets , oral food challenges, single, blind, and double-blind (DBPCFC) tests, as well as skin tests. The risk of anaphylaxis can be assessed by molecular diagnostics/component-resolved diagnosis (CRD) and by conducting a basophilic activation test (BAT). These tests allow a planned, personalized treatment based on molecular and clinical profiles. CRD can determine the individual profile of allergic molecular reactivity and enable the formulation of a prognostic judgment. Our article highlights the importance of knowing the immune mechanisms, diagnostics, and immunotherapies in FAs. Starting from observing exposure to food allergens, to identifying allergic reactions, analysing the severity of clinical manifestations, noting the possibilities of diagnosis, and illustrating adequate management strategies.
... Although most articles regarding the BAT focus on diagnosis there is pertinent data available regarding the role of the BAT in monitoring the effect of immunotherapy as well. 23 The BAT mimics the clinical phenotype of patients while other allergy tests can only detect the presence of allergen-specific IgE. Additionally, the BAT can differentiate sensitization from a true food allergy and thus segregate between allergy and tolerance, particularly in children with peanut or egg allergy. ...
The basophil activation test (BAT) is an ex vivo functional assay that measures by flow cytometry the degree of basophil degranulation after stimulation with an allergen. In recent years, there has been an increased interest in the diagnostic value of the BAT as it has the potential to mimic the clinical phenotype of sIgE sensitized patients, in contrast to allergen-specific IgE levels. This diagnostic potential would be of particular interest for food allergies present early in life such as peanut, cow’s milk and eggs, which require an expensive, time-consuming and patient unfriendly oral food challenge (OFC) for diagnosis. However, routine applications of the BAT for clinical use are not yet feasible due to the lack of standardized protocols and large clinical validation studies. This review will summarize the current data regarding the application of the BAT in food allergy (FA) for cow’s milk, egg and peanut, being the most common causes of FA in children. Additionally, it will discuss the hurdles for widespread clinical use of the BAT and possible future directions for this diagnostic procedure.
... 72 The utility of BAT in predicting OIT results has been reviewed elsewhere. 81 Briefly, several studies have shown a significant reduction in basophil reactivity during OIT. In addition, lower basophil reactivity at baseline was associated with DS following OIT and with short-term (13-week) SU. ...
... Also, the BAT is currently limited to specialized centers, and its protocol and its best outcome measure need to be better defined. 81 ...
Treatment of food allergy is a rapidly changing landscape with arguably, the most significant advancement in recent years, the transition of oral immunotherapy (OIT) to clinical practice. As an innovation, OIT is a phase of rapidly increasing demand, particularly for some allergens such as peanut, egg and milk which have substantial evidence of efficacy. However significant questions remain about how to best treat multiple food allergies and less common food allergies and how to optimize long-term safety and efficacy. This review summarizes the currently available resources for integrating food allergy OIT into clinical practice and focuses on the multiple remaining unmet needs such as providing an approach for OIT to food allergens for which there is no or limited evidence; practical issues related to food allergy treatment particularly when it is not going well; long-term outcomes and follow-up after OIT; and strategies to help meet the impending increase in demand.
... By contrast, among these same participants, 10 of 11 (91%) and 11 of 11 (100%) had positive BAT results to PEG and their administered mRNA vaccine, respectively (Figure 2). Three control participants underwent SPTs and BATs and showed typical baseline levels in control BAT assays.[6][7][8] InFigure 2, an example BAT assay histogram is shown in which the blood of a participant who had an allergic reaction to the vaccine was incubated with vaccine, anti-IgE, and normal saline, and proportion of CD63 cells was determined(Figure 2).Table 2reports summary findings from the BATs performed by condition and percentage of CD63+ of the gated basophil population in standardized whole blood BATs. ...
Importance
As of May 2021, more than 32 million cases of COVID-19 have been confirmed in the United States, resulting in more than 615 000 deaths. Anaphylactic reactions associated with the Food and Drug Administration (FDA)–authorized mRNA COVID-19 vaccines have been reported.
Objective
To characterize the immunologic mechanisms underlying allergic reactions to these vaccines.
Design, Setting, and Participants
This case series included 22 patients with suspected allergic reactions to mRNA COVID-19 vaccines between December 18, 2020, and January 27, 2021, at a large regional health care network. Participants were individuals who received at least 1 of the following International Statistical Classification of Diseases and Related Health Problems, Tenth Revision anaphylaxis codes: T78.2XXA, T80.52XA, T78.2XXD, or E949.9, with documentation of COVID-19 vaccination. Suspected allergy cases were identified and invited for follow-up allergy testing.
Exposures
FDA-authorized mRNA COVID-19 vaccines.
Main Outcomes and Measures
Allergic reactions were graded using standard definitions, including Brighton criteria. Skin prick testing was conducted to polyethylene glycol (PEG) and polysorbate 80 (P80). Histamine (1 mg/mL) and filtered saline (negative control) were used for internal validation. Basophil activation testing after stimulation for 30 minutes at 37 °C was also conducted. Concentrations of immunoglobulin (Ig) G and IgE antibodies to PEG were obtained to determine possible mechanisms.
Results
Of 22 patients (20 [91%] women; mean [SD] age, 40.9 [10.3] years; 15 [68%] with clinical allergy history), 17 (77%) met Brighton anaphylaxis criteria. All reactions fully resolved. Of patients who underwent skin prick tests, 0 of 11 tested positive to PEG, 0 of 11 tested positive to P80, and 1 of 10 (10%) tested positive to the same brand of mRNA vaccine used to vaccinate that individual. Among these same participants, 10 of 11 (91%) had positive basophil activation test results to PEG and 11 of 11 (100%) had positive basophil activation test results to their administered mRNA vaccine. No PEG IgE was detected; instead, PEG IgG was found in tested individuals who had an allergy to the vaccine.
Conclusions and Relevance
Based on this case series, women and those with a history of allergic reactions appear at have an elevated risk of mRNA vaccine allergy. Immunological testing suggests non–IgE-mediated immune responses to PEG may be responsible in most individuals.
... Several anti-allergic and anti-inflammatory drugs inhibit the release of histamine and other mediators, including cytokines and chemokines and arachidonic acid metabolites from human basophils and/or mast cells ( Table 9.5). [93][94][95][96][97] Although many of these drugs are valuable in the treatment of allergies and other inflammatory diseases, their mechanisms of action are diverse; none of the currently used drugs is mast cell-specific or basophil-specific, and the precise targets in vivo can be difficult to define. Furthermore, given the heterogeneity of mast cells at different tissue sites, 69 and perhaps even at different times during the evolution of an inflammatory insult, (e.g., initial injury, repair, chronic, or remodeling phases), agents may vary in the nature or extent of their modulatory effects on basophils and mast cells during the course of an inflammatory response or disease. ...
... 94,96 Anti-IgE has also been reported to be effective and safe in the treatment of moderate to severe allergic asthma, some cases of atopic dermatitis, and persistent allergic rhinitis and is a promising new adjunctive treatment for food allergy. [94][95][96][97] Moreover, from this pioneering approach numerous other humanized monoclonal antibody targets are being used in the clinic, including monoclonal antibodies to IL-4, IL-5, and/or their receptors, and others are in various phases of clinical testing, e.g., antibodies to IL-13 and TSLP. [95][96][97][98] The mechanisms of action of these antibodies are complex and in part likely involve direct or indirect effects on mast cells and basophils. ...
... [94][95][96][97] Moreover, from this pioneering approach numerous other humanized monoclonal antibody targets are being used in the clinic, including monoclonal antibodies to IL-4, IL-5, and/or their receptors, and others are in various phases of clinical testing, e.g., antibodies to IL-13 and TSLP. [95][96][97][98] The mechanisms of action of these antibodies are complex and in part likely involve direct or indirect effects on mast cells and basophils. ...
The Basophil Activation Test (BAT) enables flow cytometry characterization of basophil reactivity against specific allergenic molecules. The focus now revolves around democratizing this tool, but, as blood sample stability could be challenging, after having developed a simplified approach, herein, we aimed to characterize two strategies for implementing BAT in multicentric studies: store and ship blood before or after sample processing. Fresh heparin‐ and EDTA‐anticoagulated whole blood samples followed both BAT workflows: “collect, store, process & analyze” or “collect, process, store & analyze”. Storage temperatures of 18–25 °C or 2–8 °C and preservation times from 0 to 7 days were considered. Interleukin‐3 was also evaluated. With the “collect, store, process & analyze” workflow, heparin‐anticoagulated blood and 18–25 °C storage were better than other conditions. While remaining possible, basophil activation exhibited a possible reactivity decay after 24 h. Under the conditions tested, interleukin‐3 had no role in enhancing basophil reactivity after storage. Conversely, the “collect, process, store & analyze” workflow demonstrated that either heparin‐ or EDTA‐anticoagulated blood can be processed and kept up to 7 days at 18–25 °C or 2–8 °C before being analyzed. Various strategies can be implemented to integrate BAT in multicentric studies. The “collect, store, process & analyze” workflow remains a simplified logistical approach, but depending on time required to ship from the clinical centers to the reference laboratories, it might not be applicable, or should be used with caution. The “collect, process, store & analyze” workflow may constitute a workflow improvement to provide significant flexibility without impact on basophil reactivity.
Nowadays, the management of food allergies has increasingly moved from conventional oral immunotherapy (OIT) to low-dose OIT or low-dose OIT utilizing hypoallergenic foods. This shift is largely because the latter appears to induce oral tolerance with fewer adverse effects than the former. However, the mechanisms underpinning such differences remain unclear. To better understand these mechanisms, we conducted a comparative study scrutinizing the mechanisms of OIT, especially those of low-dose desensitization. We also summarized articles on low-dose OIT and low-dose OIT using hypoallergenic foods. We examined the efficacy, safety, and immunological parameters of low-dose OIT and those of low-dose OIT with hypoallergenic foods with the aim of shedding some light on low-dose OIT and its therapeutic application in inducing oral tolerance for individuals with food allergies.
