Peripheral blood eosinophil degranulation is inhibited in eosinophilic esophagitis:  implications for non-invasive assessment of disease activity
Monday, March 6, 2017: 2:45 PM
Rooms B312-B313 (Georgia World Congress Center, Building B)
Benjamin L. Wright, MD, , , , ,
Rationale:   Eosinophil peroxidase (EPX) is an eosinophil-specific granule protein responsible for mediating eosinophil effector functions. We have established that tissue EPX correlates with symptoms of eosinophilic esophagitis (EoE). We hypothesized that serum EPX would be elevated in EoE subjects and serve as a potential biomarker.

Methods:   Prospectively collected serum from 19 subjects with incident EoE prior to treatment and 20 non-EoE controls were tested for the eosinophil granule proteins EPX, eosinophilic cationic protein (ECP) and eosinophil derived neurotoxin (EDN) using ELISA.  Matching esophageal tissue sections were stained and assessed for EPX deposition using a histopathologic scoring algorithm.

Results:   Median absolute eosinophil counts (AEC) in the serum were significantly elevated in EoE subjects compared to controls (300 vs. 100 cells/ul, p = 0.001).  Absolute median serum EPX, ECP and EDN did not differ between groups; however, when normalized for AEC, EoE subjects had significantly lower EPX/AEC (2.56 vs. 6.96, p = 0.002, AUC 0.79 (0.64, 0.94 95% CI)) and EDN/AEC ratios (0.07 vs. 0.155, AUC 0.74 (0.59, 0.90 95% CI)).  Differences in ECP/AEC ratios were not observed.  Esophageal biopsies from EoE subjects demonstrated marked EPX deposition compared to controls (median EPX monoclonal antibody score 47 vs. 0, p < 0.0001)

Conclusions:   In contrast to increased tissue EPX levels, EoE subjects had significantly lower serum EPX when normalized for AEC.  EDN/AEC ratios were also lower in EoE subjects.  These findings suggest degranulation is inhibited until eosinophils reach the site of tissue infiltration.  Investigation of EPX/AEC and EDN/AEC as peripheral markers of EoE activity should be conducted.