Like Eosinophilic Esophagitis, Reflux Esophagitis with Moderate to Abundant Eosinophils Is a Type 2 Immune Response with IgE-Staining Mast Cells
Fred Clayton, Laura A Vinson, Kathryn A Peterson. University of Utah, Salt Lake City, UT
Background: Aspects of the cause of eosinophilic esophagitis (EoE) and its relationship to reflux esophagitis with abundant eosinophils are unclear. Distinguishing them on a pathologic basis is problematic.
Design: 18 adults with recently diagnosed EoE were given an elemental diet, generally for 4 weeks. The histologic findings, immunofluorescent and immunoperoxidase staining, and ELISA assays were done on esophageal biopsies before and after treatment. Also examined were 9 to 11 subjects each in the following categories: normal controls, reflux esophagitis with few eosinophils, and reflux esophagitis with ≥3 eosinophils/hpf (RE-E), but not meeting consensus EoE criteria. Esophageal slides from 56 autopsies (without history of esophageal disease) were also examined for IgE-staining mast cells.
Results: On the elemental diet, mean tissue eosinophil content decreased from 54 to 10/hpf. In EoE (before and after treatment) and RE-E, type 2 immune response-related nuclear transcription factors (phosphoSTAT5, phosphoSTAT6, and GATA3) were abundant in the mononuclear inflammatory cells and were dramatically increased compared to normal controls (p<0.05). More than 3 intraepithelial IgE-staining mast cells were present in 96% of EoE cases, 50% of RE-E cases, and only 3% of normal controls (p<0.01). Eotaxin-3 by ELISA and dendritic cells (CD11c staining) also were more abundant in EoE and RE-E than in normal controls (<0.01 to 0.05). Findings which best distinguished untreated EoE from RE-E and treated EoE were tissue basophil and CRTH2 immunostaining. Basophils and CRTH2-staining cells were present in 81% and 74% of untreated EoE, but only in 11% and 0% of RE-E cases and 10% and 0% of treated EoE patients, respectively (p<0.01 for EoE treated versus untreated, and RE-E versus untreated EoE). Immunostaining results for treated EoE and RE-E were not statistically different, except for a less than 2-fold higher GATA3 content in RE-E relative to treated EoE (p=0.03).
Conclusions: EoE is a type 2 adaptive immune response, possibly allergic. RE-E was mostly similar to EoE after treatment, having a type 2 polarized inflammatory response with eosinophils, eotaxin-3, appropriate nuclear transcription factors, and increased IgE-staining mast cells. Both lacked the tissue basophils, CRTH2, and the degree of inflammation seen in active, untreated EoE. Further work is needed to determine whether RE-E is a precursor to EoE or, in some cases, a mild, relatively inactive form or phase of EoE.
Tuesday, March 5, 2013 8:30 AM
Proffered Papers: Section D, Tuesday Morning