Eosinophil beta1 integrin activation as a biomarker for eosinophilic esophagitis

University Of Wisconsin-Madison, Madison WI

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Abstract

Abstract: The greatest challenge in managing eosinophilic esophagitis (EoE) is the monitoring of disease activity and appropriating therapy. EoE is a newly described chronic esophageal inflammatory disease manifesting as dysphagia or food obstruction in adults. Management goals for EoE direct treatment towards reducing esophageal mucosal inflammation and preventing stricture of the esophagus. Interestingly, neither endoscopic findings nor counted numbers of eosinophils on biopsy directly correlate to severity or frequency of EoE symptoms making monitoring disease activity challenging. To date, the standard of care for disease surveillance is repeat endoscopies with biopsies as there are no other validated symptom tools or biomarkers to replace pathology-based monitoring. Standard treatment options of dietary modifications or topical steroid therapy are difficult to implement and require both constant vigilance to avoid food triggers and serial invasive procedures to gauge endoscopic appearance and histology for response. The resolution of inflammation is not always assured and persistent eosinophilic inflammation in the esophagus increases risk for EoE symptoms and can lead to significant complications such as esophageal stricture. Thus, there is a critical need for rapid and accurate evaluation of disease activity in order to provide timely feedback on efficacy of treatment. The expression and activation of cell surface markers on eosinophils is an essential step in trafficking into target tissues such as the esophagus. Several studies examined the expression of eosinophil cell surface markers including integrin ? and ? subunits suggesting potential utility in EoE. However, no study on eosinophil-surface biomarkers in EoE has followed patients over time, correlated biomarkers with symptoms, or included integrin activation as a biomarker. We have previously described a ?1 integrin conformational change as a marker for eosinophil activation. We hypothesize that eosinophil activation in EoE, measured primarily by ?1 integrin activation, correlates with esophageal eosinophil count, histology, endoscopic appearance, and esophageal symptoms and represents a biomarker to guide EoE management. We propose to test this hypothesis by completing the following aims: 1) identify relationship between eosinophil activation and EoE disease activity, and 2) demonstrate reduction in eosinophil activation with treatment of EoE.