Abstract
BackgroundPerioperative hypersensitivity reaction (HR) is an IgE-FcϵRI-mediated hypersensitivity reaction with degranulation and activation of mast cells and basophils. Several studies have focused on assessing the degranulation and activation of mast cells and basophils to diagnose and predict the prognosis of drug induced HR. However, it is challenging to isolate sufficiently pure mast cells and basophils from human sources to investigate. Effective biomarkers to assess mast cells and basophils activation in vivo could potentially have high diagnostic and prognostic values. In the present study, we investigated EVs pelleted from serum in patients with succinylated gelatin induced HR.MethodsExtracellular vesicles (EVs) were isolated using a total exosome isolation kit and ultracentrifugation, characterized by Western blot, transmission electron microscopy, and nanoparticle tracking analysis. Basophils were isolated from fresh peripheral blood by negative selection using Basophil Isolation Kit II. Human mast cell line was stimulated with IL4. The expression levels of proteins related to the hypersensitive response were evaluated by Western blotting and flow Cytometer. Histamine and tryptase levels were tested using a commercial ELISA kit, and gene expression of inflammatory mediators was evaluated by qRT-PCR. The receiver operating characteristic (ROC) curve was used to evaluate the specificity and sensitivity of biomarker in predicting HR.ResultsThe concentration of EVs and protein expression level of CD63, FcϵRI, CD203c and tryptase were significantly (p< 0.05) increased in HR samples. The expression level of mast cell/basophil specific CD203c were significantly increased in EVs derived from serum and basophils of HR patients, and the CD203c+-EVs production in mast cells is dramatically increased in the presence of IL4, which positively correlated with histamine, tryptase and inflammatory mediators. Moreover, the ROC curve of EVs concentration and CD203c expression indicated that CD203c+-EVs had a strong diagnostic ability for HR.ConclusionSerum CD203c+-EVs serves as a novel diagnostic and prognostic biomarker for HR.
Highlights
Perioperative hypersensitivity reaction (HR) is caused by a rapid hypersensitivity reaction triggered by perioperative drugs that affects multiple tissues, organs, and systems throughout the body and poses a serious threat to the lives of surgical patients
We first found that the expression level of mast cell/basophil specific biomarker CD203c were significantly increased in Extracellular vesicles (EVs) derived from serum and basophils of HR patients, and the CD203c+-EVs production in mast cells is dramatically increased in the presence of IL4, which positively correlated with histamine, tryptase and inflammatory mediators
EVs morphology was monitored by transmission electron microscopy (TEM) (Figures 1B, C), and particle size distribution and concentration were tested by nanoparticle tracking analysis (NTA) (Figures 1D, E)
Summary
Perioperative hypersensitivity reaction (HR) is caused by a rapid hypersensitivity reaction triggered by perioperative drugs (usually anesthetics) that affects multiple tissues, organs, and systems throughout the body and poses a serious threat to the lives of surgical patients. It is challenging to isolate sufficiently pure mast cells and basophils from human sources to study them. Studies have been focused on exploring potential biomarkers of mast cell and basophil activation in vivo. Effective biomarkers to assess mast cell and basophil activation in vivo could potentially have high diagnostic and prognostic values, and the availability of a sensitive, specific, rapid, and reliable test to diagnose HR would be more than welcome. Several studies have focused on assessing the degranulation and activation of mast cells and basophils to diagnose and predict the prognosis of drug induced HR. It is challenging to isolate sufficiently pure mast cells and basophils from human sources to investigate. Effective biomarkers to assess mast cells and basophils activation in vivo could potentially have high diagnostic and prognostic values. We investigated EVs pelleted from serum in patients with succinylated gelatin induced HR
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