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.
View Article and Find Full Text PDFJ Allergy Clin Immunol Pract
November 2024
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.
View Article and Find Full Text PDFA 56-year-old man with well-controlled human immunodeficiency virus, anxiety, depression, and hypercholesterolemia developed acute urticaria, lip angioedema, and respiratory distress after consumption of a cheeseburger, French fries, lemonade, and ibuprofen. He was evaluated in the emergency department and, during admission, developed asystole, diaphoresis, pallor, and a brief episode of posturing that was treated with two doses of epinephrine. Results of the initial workup with electrocardiogram, troponin, complete blood cell count, and comprehensive metabolic panel were normal.
View Article and Find Full Text PDFBackground: 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.
Background: Studies suggest that oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) for food allergy hold promise; however, the immunologic mechanisms underlying these therapies are not well understood.
Objective: We sought to generate insights into the mechanisms and duration of suppression of immune responses to peanut during immunotherapy.
Methods: Blood was obtained from subjects at baseline and at multiple time points during a placebo-controlled trial of peanut OIT and SLIT.
Sublingual (SLIT) and oral immunotherapy (OIT) are promising treatments for food allergy, but underlying mechanisms are poorly understood. Dendritic cells (DCs) induce and maintain Th2-type allergen-specific T cells, and also regulate innate immunity through their expression of Toll-like receptors (TLRs). We examined how SLIT and OIT influenced DC innate and adaptive immune responses in children with IgE-mediated cow's milk (CM) allergy.
View Article and Find Full Text PDFBackground: Dendritic cells (DCs) and other professional antigen-presenting cells express a variant of the high-affinity IgE receptor known as alphagamma(2), which, on the basis of in vitro findings, has long been implicated to function in facilitating allergen uptake and presentation to T(H) cells.
Objectives: To use omalizumab as an in vivo tool to neutralize IgE binding to circulating dendritic cells and to assess whether this results in altered DC-dependent T-cell responsiveness to allergen ex vivo.
Methods: Subjects with cat allergy were enrolled in a 3.
Although IL-3 is commonly recognized for its growth factor-like activity, in vitro studies have long demonstrated a unique capacity for this cytokine to also augment the proinflammatory properties and phenotype of human basophils. In particular, basophils secrete mediators that are hallmarks in allergic disease, including vasoactive amines (e.g.
View Article and Find Full Text PDFBackground: Immature human blood monocytoid dendritic cells (mDCs) express high-affinity receptors for IgE (Fc epsilon RI), yet their exact function and regulation remain poorly understood.
Objective: We sought to characterize Fc epsilon RI-dependent cytokine responses and their regulation in circulating human blood mDCs.
Methods: Fc epsilon RI-dependent cytokine responses of circulating mDCs were studied by using anti-Fc epsilon RI alpha stimulation.
Background: Functional significance for the alphagamma(2) variant of the high-affinity IgE receptor (FcepsilonRI) reportedly expressed on human dendritic cell subtypes remains poorly understood. Studies show that immature plasmacytoid dendritic cells (pDCs) secrete large quantities of TNF-alpha and IL-6 when directly stimulated with anti-IgE antibody. This mode of activation, however, reduces Toll-like receptor 9 (TLR9) expression in pDCs and their ability to mount an IFN-alpha response when subsequently activated with oligodeoxynucleotide containing CpG.
View Article and Find Full Text PDFPlasmacytoid dendritic cells (pDC) express not only TLR9 molecules through which ligation with CpG DNA favors Th1 responses but also possess IgE receptors (FcepsilonRI) implicated in allergen presentation and induction of Th2 responses. This dichotomy prompted an investigation to determine whether TLR9- and IgE receptor-mediated responses oppose one another in pDC by affecting receptor expression and associated functional responses. Results showed that IgE cross-linking reduced TLR9 in pDC and inhibited the capacity of these cells to secrete IFN-alpha when stimulated with the CpG oligodeoxynucleotide (ODN)-2216.
View Article and Find Full Text PDFBackground: Toll-like receptor (TLR) molecules play a critical role in directing the course of acquired immunity, including that associated with allergic disease, by recognizing specific microbial products that activate immune cells for effector functions.
Objective: We investigated whether human basophils express 2 such molecules (TLR2 and TLR4), and assessed whether putative ligands for these receptors activate nuclear factor kappaB (NFkappaB) and modulate mediator release and cytokine secretion either alone or in response to stimulation.
Methods: Toll-like receptor expression was assessed by using RT-PCR and flow cytometry.
Background: Innate immune responses play a critical role in determining the course of acquired immunity, including that associated with allergic disease. Type I interferons, which are generated early in these reactions, are important soluble factors that prime for TH1-like activity.
Objective: Because human basophils secrete IL-4 and IL-13 in response to both IgE-dependent and IgE-independent stimuli, we tested whether IFN-alpha, a major type I IFN, affects the production of these TH2 cytokines and/or mediator release from these cells.