title: Molecular diagnosis of eosinophilic esophagitis by gene expression profiling.
abstract: OBJECTIVE
  Gene expression profiling provides an opportunity for definitive diagnosis but has not yet been well applied to inflammatory diseases. Here we describe an approach for diagnosis of an emerging form of esophagitis, eosinophilic esophagitis (EoE), which is currently diagnosed by histology and clinical symptoms.
  
  
  METHODS
  We developed an EoE diagnostic panel (EDP) comprising a 96-gene quantitative polymerase chain reaction array and an associated dual-algorithm that uses cluster analysis and dimensionality reduction using a cohort of randomly selected esophageal biopsy samples from pediatric patients with EoE (n = 15) or without EoE (non-EoE controls, n = 14) and subsequently vetted the EDP using a separate cohort of 194 pediatric and adult patient samples derived from both fresh or formalin-fixed, paraffin-embedded tissue: active EoE (n = 91), control (non-EoE and EoE remission, n = 57), histologically ambiguous (n = 34), and reflux (n = 12) samples.
  
  
  RESULTS
  The EDP identified adult and pediatric patients with EoE with approximately 96% sensitivity and approximately 98% specificity, and distinguished patients with EoE in remission from controls, as well as identified patients exposed to swallowed glucorticoids. The EDP could be used with formalin-fixed, paraffin-embedded tissue RNA and distinguished patients with EoE from those with reflux esophagitis, identified by pH-impedance testing. Preliminary evidence showed that the EDP could identify patients likely to have disease relapse after treatment.
  
  
  CONCLUSIONS
  We developed a molecular diagnostic test (referred to as the EDP) that identifies patients with esophagitis in a fast, objective, and mechanistic manner, offering an opportunity to improve diagnosis and treatment, and a platform approach for other inflammatory diseases.
authors: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors: Ting
authors: T
authors: Wen
authors: Emily M
authors: EM
authors: Stucke
authors: Tommie M
authors: TM
authors: Grotjan
authors: Katherine A
authors: KA
authors: Kemme
authors: J Pablo
authors: JP
authors: Abonia
authors: Philip E
authors: PE
authors: Putnam
authors: James P
authors: JP
authors: Franciosi
authors: Jose M
authors: JM
authors: Garza
authors: Ajay
authors: A
authors: Kaul
authors: Eileen C
authors: EC
authors: King
authors: Margaret H
authors: MH
authors: Collins
authors: Jonathan P
authors: JP
authors: Kushner
authors: Marc E
authors: ME
authors: Rothenberg
mesh_terms: D000328:Adult; D000367:Age Factors; D001706:Biopsy; D016022:Case-Control Studies; D002648:Child; D016000:Cluster Analysis; D003937:Diagnosis, Differential; D057765:Eosinophilic Esophagitis / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D004942:Esophagitis, Peptic / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D004947:Esophagus / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D057089:Pathology, Molecular / Q000379:methods*; D011379:Prognosis; D012680:Sensitivity and Specificity; D059467:Transcriptome / Q000235:genetics*
keywords: AUC; Diagnostic Panel; EDP; EGID; EoE; EoE Transcriptome; Eosinophil; FFPE; Fluidic Card; GERD; GI; HPF; MII; NL; Nonerosive Reflux Disease; ROC; Signature; area under the curve; eosinophilic esophagitis; eosinophilic esophagitis diagnostic panel; eosinophilic gastrointestinal disorder; formalin-fixed, paraffin-embedded; gastroesophageal reflux disease; gastrointestinal; high-power field; multichannel intraluminal impedance; normal; receiver operating characteristic
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