Determination of eosinophilic esophagitis

Abstract

Eosinophilic esophagitis (EE), an emerging disorder with poorly understood pathogenesis, was examined. Esophageal tissue was analyzed by a genome wide microarray expression analysis. EE patients had a transcript signature involving 1% of the genome that was conserved across gender, age, and atopic status, and was distinct from that associated with chronic esophagitis (CE). The eosinophil specific chemokine eotaxin-3 was the top induced gene compared with normal controls. Levels C of eotaxin-3 mRNA and protein correlated with disease severity. A single nucleotide polymorphism in the human eotaxin-3 gene conferred susceptibility to disease. Mice deficient in the eotaxin-3 receptor (CCR-3) were protected from experimental EE. Eotaxin-3 was identified as a specific effector molecule, biomarker, and genetic risk factor for EE, and distinguished EE from CE.

1 . A method comprising:
 determining an expression profile of at least one gene selected from at least one of SEQ ID NOS. 1-574 that is activated or inhibited in an esophagus of a human patient,   comparing the patient's expression profile of the at least one gene with a human expression profile for the gene in eosinophilic esophagitis, and   determining that the patient has a propensity for eosinophilic esophagitis if there is a difference in relative expression between the at least one gene in the patient and in the human gene expression profile.   
     
     
         2 . The method of  claim 1  wherein a gene cluster is compared. 
     
     
         3 . The method of  claim 1  wherein the gene is selected from the group consisting of Chemokine (C-C motif) ligand 26, periostin, osteoblast specific factor, tumor necrosis factor, alpha-induced protein 6, cadherin-like 26; arachidonate 15-lipoxygenase, pro-melanin-concentrating hormone, chemokine (C-X-C motif) ligand 1, immunoglobulin lambda joining 3, transmembrane protein 16A, apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A, immunoglobulin heavy constant gamma 1 (Glm marker), FLJ16025 protein, ubiquitin D, immunoglobulin J polypeptide, linker protein for immunoglobulin, hypothetical protein FLJ33069, carboxypeptidase A3 (mast cell), similar to immunoglobulin kappa light chain variable region 011, Charcot-Leyden crystal protein, hypothetical protein MGC27165, pleckstrin homology-like domain, family B, member 2, hypothetical protein F1123259, immunoglobulin kappa constant, epiplakinl, chemokine (C-X-C motif) ligand 6, filaggrin, erythrocyte membrane protein band 4.1-like 3, sorting nexin 19, 26 serine protease, carboxylesterase 1 (monocyte/macrophage serine esterase 1), glycogen synthase 2 (liver), cytidine deaminase, GSGL541, or cysteine-rich secretory protein 3. 
     
     
         4 . A method to enhance differentiation between eosinophilic esophagitis and chronic esophagitis, the method comprising:
 determining signature esophageal gene transcripts for each of eosinophilic esophagitis and chronic esophagitis, the gene transcript encoding a cellular function selected from the group consisting of cell growth, cell maintenance, cell communication, cell response to stress, cell signal transduction, cell response to external stimulus, or cell immune response, and   determining the difference in each of eosinophilic esophagitis and chronic esophagitis signature esophageal gene transcripts to distinguish eosinophilic esophagitis from chronic esophagitis.   
     
     
         5 . The method of  claim 4  wherein the transcript is selected from SEQ ID NOS: 1-574. 
     
     
         6 . The method of  claim 4  wherein the transcript is a signature for a mast cell gene. 
     
     
         7 . The method of  claim 4  wherein the transcript is selected from the group consisting of Chemokine (C-C motif) ligand 26, periostin, osteoblast specific factor, tumor necrosis factor, alpha-induced protein 6, cadherin-like 26; arachidonate 15-lipoxygenase, pro-melanin-concentrating hormone, chemokine (C-X-C motif) ligand 1, immunoglobulin lambda joining 3, transmembrane protein 16A, apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A, immunoglobulin heavy constant gamma 1 (Glm marker), FLJ16025 protein, ubiquitin D, immunoglobulin J polypeptide, linker protein for immunoglobulin, hypothetical protein FLJ33069, carboxypeptidase A3 (mast cell), similar to immunoglobulin kappa light chain variable region 011, Charcot-Leyden crystal protein, hypothetical protein MGC27165, pleckstrin homology-like domain, family B, member 2, hypothetical protein F1123259, immunoglobulin kappa constant, epiplakinl, chemokine (C-X-C motif) ligand 6, filaggrin, erythrocyte membrane protein band 4.1-like 3, sorting nexin 19, 26 serine protease, carboxylesterase 1 (monocyte/macrophage serine esterase 1), glycogen synthase 2 (liver), cytidine deaminase, GSGL541, cysteine-rich secretory protein 3, and combinations thereof. 
     
     
         8 . The method of  claim 7  wherein the transcript induced to the greatest extent in eosinophilic esophagitis is eotaxin-3. 
     
     
         9 . The method of  claim 8  wherein the level of eotaxin-3 transcript positively correlates with eosinophilic esophagitis severity. 
     
     
         10 . The method of  claim 8  wherein the level of eotaxin-3 transcript positively correlates with blood eosinophil levels. 
     
     
         11 . The method of 6 wherein a single nucleotide polymorphism of +2496 (G/T) in a gene for eotaxin-3 is a marker for the patient's susceptibility to eosinophilic esophagitis. 
     
     
         12 . (canceled) 
     
     
         13 . (canceled) 
     
     
         14 . A method to differentiate eosinophilic esophagitis from chronic esophagitis, the method comprising:
 determining a level of an eotaxin-3 transcript in a patient biological sample, determining whether the patient's eotaxin-3 transcript level is increased over an eotaxin-3 level in a control,   the patient having an increased risk for eosinophilic esophagitis versus chronic esophagitis with an increased level of the eotaxin-3 transcript in the patient sample.   
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . (canceled)