INCREASED EOSINOPHIL GRANULE PROTEIN PRODUCTION IN CHRONIC SPONTANEOUS URTICARIA

Abstract

<h3>Introduction</h3> Chronic spontaneous urticaria (CSU) lesional and non-lesional skin reveals increased numbers of eosinophils, but the exact role of eosinophils in CSU pathogenesis remains unknown. A pathogenic role for eosinophils in CSU was supported by the results of a recent clinical trial demonstrating the efficacy of benralizumab in CSU. Previous studies have identified increased levels of major basic protein (MBP) and eosinophilic cationic protein (ECP) in the sera and skin of CSU subjects; however, eosinophil peroxidase (EPO), the granule protein uniquely expressed by eosinophils, and eosinophil-derived neurotoxin (EDN) were not examined. Therefore, we sought to determine whether eosinophil granule proteins (EGPs) are increased in CSU. <h3>Methods</h3> Sera from CSU subjects (n=11) and healthy controls (n=1) were collected and sent to the NIH Human Eosinophil Section for analysis with their novel multiplex immunoassay which simultaneously measures concentrations of MBP, ECP, EDN, and EPO using Luminex xMAP technology. CSU subjects completed disease activity surveys and complete blood count differentials were analyzed. <h3>Results</h3> Mean concentrations of MBP (1329.23 vs 399.55ng/ml), ECP (285.87 vs 45.31ng/ml), EDN (349.43 vs 38.53ng/ml), and EPO (54.96ng/ml vs undetectable) were markedly increased in CSU subjects compared to the healthy control. We found no correlation between eosinophil counts and granule protein levels, or with Urticaria Activity Scores. <h3>Conclusions</h3> Our results suggest that unique pathways may be activated in a subset of patients with CSU which led to the production of large quantities of EGPs. Additional research is needed to understand the pathways responsible for producing these granule proteins in CSU and their clinical impact.