Defining Optimal Basophil Passive Sensitisation Parameters.

Background: Detecting drug-specific IgE (sIgE) is crucial for diagnosing immediate drug-induced hypersensitivity reactions. Basophil activation tests serve as a method to determine the presence of drug-sIgE, highlighting the importance of optimising the assay. Optimisation involves considering multiple factors to ensure sensitisation helps detect an antigen sIgE.

Peanut-specific IgG subclasses as biomarkers of peanut allergy in LEAP study participants.

Antigen-specific IgG2 and IgG3 are rarely measured in food allergy clinical trials despite known function in preventing mast cell and basophil activation. Our objective was to determine whether measuring peanut-specific IgG2 and IgG3 levels would correlate with peanut allergy status. Peanut-specific IgG subclasses were measured via ELISA assays in Learning Early About Peanut allergy (LEAP) trial participants at 5 years of age and were correlated with peanut allergy vs peanut sensitization vs non-peanut allergic and peanut consumption vs peanut avoidance.

A Skin Testing Strategy for Non-IgE-Mediated Reactions Associated With Vancomycin.

Background: Vancomycin infusion reaction (VIR), reportedly mediated through Mas-Related G Protein-Coupled Receptor-X2, is the primary vancomycin-induced immediate drug reaction. Clinically, distinguishing the underlying drug-induced immediate drug reaction mechanisms is crucial for future treatment strategies, including drug restriction, re-administration, and pretreatment considerations. However, the lack of validated diagnostic tests makes this challenging, often leading to unnecessary drug restriction.

A phase II study of Bruton's tyrosine kinase inhibition for the prevention of anaphylaxis.

BACKGROUNDIgE-mediated anaphylaxis is a potentially fatal systemic allergic reaction for which there are no currently FDA-approved preventative therapies. Bruton's tyrosine kinase (BTK) is an essential enzyme for IgE-mediated signaling pathways and is an ideal pharmacologic target to prevent allergic reactions. In this open-label trial, we evaluated the safety and efficacy of acalabrutinib, a BTK inhibitor that is FDA approved to treat some B cell malignancies, in preventing clinical reactivity to peanut in adults with peanut allergy.

Bruton's tyrosine kinase inhibition for the prevention of anaphylaxis: an open-label, phase 2 trial.

IgE-mediated anaphylaxis is a potentially fatal systemic allergic reaction for which there are no known preventative therapies. Bruton's tyrosine kinase (BTK) is an essential enzyme for IgE-mediated signaling pathways, and is an ideal pharmacologic target to prevent allergic reactions. In this open-label trial (NCT05038904), we evaluated the safety and efficacy of acalabrutinib, a BTK inhibitor that is FDA-approved to treat some B cell malignancies, in preventing clinical reactivity to peanut in adults with IgE-mediated peanut allergy.

Biological screening of a unique drug library targeting MRGPRX2.

Background: Allergic drug reaction or drug allergy is an immunologically mediated drug hypersensitivity reaction (DHR). G-protein coupled receptors (GPCRs) are common drug targets and communicate extracellular signals that initiate cellular responses. Recent evidence shows that GPCR MRGPRX2 is of major importance in IgE-independent pseudo-allergic DHRs based on the suspected interactions between many FDA-approved peptidergic compounds and MRGPRX2.

Response of peripheral blood basophils in subjects with chronic spontaneous urticaria during treatment with omalizumab.

Background: Treatment of patients with asthma or food allergy with omalizumab results in several consistent changes in circulating basophils. The multiple basophil phenotypes observed in patients with chronic spontaneous urticaria (CSU) present some unique attributes that may not respond in a similar fashion to patients with asthma or food allergy. As part of a clinical study on the therapeutic outcomes of omalizumab treatment in CSU, the basophil compartment was examined for changes in characteristics predicted by prior studies.

The efficacy of omalizumab treatment in chronic spontaneous urticaria is associated with basophil phenotypes.

Background: The mechanisms underlying disease pathogenesis in chronic spontaneous urticaria (CSU) and improvement with omalizumab are incompletely understood.

Objectives: This study sought to examine whether the rate of clinical remission is concordant with baseline basophil features or the rate of change of IgE-dependent functions of basophils and/or plasmacytoid dendritic cells during omalizumab therapy.

Methods: Adults (n = 18) with refractory CSU were treated with omalizumab 300 mg monthly for 90 days.

The relationship between released soluble FceRI-alpha and its cell surface density on human basophils.

Background: The IgE-mediated activation of mast cells and basophils results in the secretion of many substances, including the release of FceRI-alpha subunit. This released alpha subunit can bind IgE and it may act as a down-regulator of subsequent IgE-dependent reactions. However, previous studies do not observe loss of the mass of FceRI-alpha associated with the cells, at least not for human basophils.

Targeting the FcεRI Pathway as a Potential Strategy to Prevent Food-Induced Anaphylaxis.

Despite attempts to halt it, the prevalence of food allergy is increasing, and there is an unmet need for strategies to prevent morbidity and mortality from food-induced allergic reactions. There are no known medications that can prevent anaphylaxis, but several novel therapies show promise for the prevention of food-induced anaphylaxis through targeting of the high-affinity IgE receptor (FcϵRI) pathway. This pathway includes multiple candidate targets, including tyrosine kinases and the receptor itself.

Modulating the Human Basophil Phenotype During Its Development and Maturation: Basophils Derived from In Vitro Cultures of CD34 Progenitor Cells.

Historically, the human basophil that is studied experimentally comes from peripheral blood. But there is evidence that only a short portion of the basophil life cycle related to IgE-mediated function occurs in the blood. The same evidence suggests that IgE-mediated functionality is present for 5-7 days in the bone marrow (or other tissues) during which the cell modulates its phenotype according to local conditions.

Identifying regulatory pathways of spleen tyrosine kinase expression in human basophils.

Background: Expression levels of spleen tyrosine kinase (SYK), a critical signaling tyrosine kinase in basophils, are uniquely low relative to all other circulating leukocytes, and levels are highly variable in the population.

Objective: We sought to determine whether transcriptional regulation of SYK through unique silencing of the SYK gene determines its basophil-specific expression patterns.

Methods: Culture-derived basophils (CD34B cells) were derived from cultures of CD34 progenitor cells by using 2 methods (G1 or G3).

Dependence of Optimal Histamine Release on Cell Surface IgE Density on Human Basophils: Nature of the Stimulus.

Background: The characteristics of the aggregation reaction that follows allergen binding to cell surface IgE on basophils and mast cells depend on a variety of factors that include the density of IgE and the affinity of the allergen for IgE. For simple bivalent stimuli, one prediction is that the location of the optimum for aggregation is not dependent on IgE density, only the affinity for IgE. However, this behavior does not occur for stimulation with an anti-IgE antibody (Ab) during the treatment of patients with omalizumab.

Autoantibodies to IgE and FcεRI and the natural variability of spleen tyrosine kinase expression in basophils.

Background: Secretion from human basophils and mast cells requires spleen tyrosine kinase (SYK) activity, but SYK expression is highly variable in the general population, and this variability predicts the magnitude of IgE-mediated secretion. One known mechanism of modulating SYK expression in human basophils is aggregation of FcεRI.

Objective: This study examines the possibility that functional autoantibodies are present in a wide variety of subjects and, in particular, subjects whose basophils poorly express SYK.

FceRI density and spontaneous secretion from human basophils.

Mast cells and basophils depend on aggregation of the high-affinity IgE receptor, FceRI, to initiate secretion. A variety of studies have shown that FceRI densities vary 100 fold among subjects' basophils and it has been speculated that high densities might be responsible for unusual behaviors of the cells, notably sensitivity to certain monomeric IgE antibodies or spontaneous release. These studies experimentally examined the density dependence of spontaneous release and signaling element expression in subjects' basophils with FceRI densities ranging from approximately 6000 to 600,000 per cell.

Recovery from desensitization of IgE-dependent responses in human lung mast cells.

Background: Clinical desensitization and oral food immunotherapy are therapeutic interventions that allow individuals who react adversely to an allergen (drug or food) to be made tolerant to the allergen. However, tolerance is brief, and allergen hypersensitivity can recur within days following allergen withdrawal.

Objective: We hypothesize that the reason these treatments are temporary reflects rapid recovery of mast cells from a desensitized state.

Pros and Cons of Clinical Basophil Testing (BAT).

Purpose Of Review: We review basophil testing by flow cytometry with an emphasis on advantages and disadvantages.

Recent Findings: There are many tools available to assess the presence and severity of allergic diseases in patients. For 50 years, peripheral blood basophils have been used as tools to study these diseases.

Stability of Syk protein and mRNA in human peripheral blood basophils.

In human basophils, Syk expression is 10-fold lower than most other types of leukocytes. There are indirect studies that suggest that Syk protein is highly unstable (a calculated half-life less than 15 min) in human peripheral blood basophils. Therefore, in these studies, Syk stability was directly examined.