title: Extracellular Eosinophil Granule Protein Deposition in Ringed Esophagus with Sparse Eosinophils.
abstract: BACKGROUND
  Eosinophilic esophagitis (EoE) remains difficult to classify because of varying presentations. Not uncommonly, patients present with symptoms of esophageal dysfunction and have esophageal changes on endoscopy resembling EoE but without >15 eosinophils/HPF. Patients with low numbers of eosinophils in esophageal biopsy specimens may have esophageal changes and symptomatic disease brought about by eosinophil granule protein deposition without recognizable intact cells.
  
  
  OBJECTIVE
  To determine whether extracellular eosinophil granule protein deposition is present in the esophagi of patients with low eosinophil numbers who have clinical symptoms and characteristic endoscopic esophageal changes of EoE including ringed esophagus (RE).
  
  
  METHODS
  Esophageal biopsy specimens were studied from eight EoE patients with >15 eosinophils per high power field (HPF) and nine patients with RE (<15 eosinophils/HPF). The specimens were analyzed for eosinophil granule proteins, major basic protein 1 (eMBP1) and eosinophil-derived neurotoxin (EDN), by indirect immunofluorescence.
  
  
  RESULTS
  Both EoE and RE showed positive EDN and eMBP1 extracellular deposition; control esophagus showed minimal or none. Comparing EoE and RE, extracellular EDN and eMBP1 were similar except that EDN in EoE was greater in the distal esophagus.
  
  
  CONCLUSIONS
  This study highlights the importance of assessing eosinophil granule protein deposition in esophageal disease with potential eosinophil involvement. Persistent/progressive esophageal changes may be brought about by eosinophil granule proteins despite low numbers of intact cells. The meaning of "resolution" in EoE may need to be redefined based on numbers of esophageal eosinophils, extracellular eosinophil granule protein deposition, and subsequent clinical course of patients.
authors.affiliation: Department of Medicine, Health Sciences Center, University of Utah, Salt Lake City, UT, USA, kathryn.peterson@hsc.utah.edu.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Peterson
authors.forename: William J
authors.initials: WJ
authors.lastname: Cobell
authors.forename: Frederic C
authors.initials: FC
authors.lastname: Clayton
authors.forename: Chaya
authors.initials: C
authors.lastname: Krishnamurthy
authors.forename: Jian
authors.initials: J
authors.lastname: Ying
authors.forename: Leonard F
authors.initials: LF
authors.lastname: Pease
authors.forename: Hedieh
authors.initials: H
authors.lastname: Saffari
authors.forename: Ann
authors.initials: A
authors.lastname: Georgelas
authors.forename: John
authors.initials: J
authors.lastname: Fang
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Gleich
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Leiferman
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D047093:Eosinophil Major Basic Protein / Q000032:analysis*; D047208:Eosinophil-Derived Neurotoxin / Q000032:analysis*; D057765:Eosinophilic Esophagitis / Q000378:metabolism* / Q000473:pathology*; D004804:Eosinophils; D004947:Esophagus / Q000737:chemistry* / Q000473:pathology*; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D047208:Eosinophil-Derived Neurotoxin; D047093:Eosinophil Major Basic Protein