Esophagitis, Eosinophilic, 1

Watchlist

(log in to enable)

Retrieved

2019-09-22

Source

Omim

Trials

—

Genes

TSLP, CAPN14, TRIM8, TNK2, STAT6, JAZF1, EMSY, CCL26, IL13, IFFO2, HSF2BP, LINC02588, ANKRD27, CCDC81, MEAK7, SHROOM3, KIF17, IL5, CLEC16A, DCC, TIMP2, P2RX6, LINC02240, XKR6, CAPN5, CEP295NL, TGFB1, POSTN, FLG, TNF, DSG1, IL33, CCL11, FOXP3, ATP12A, ATP4A, IL4, IL6, IL15, EPC2, SPINK7, WDR36, CLDN7, CPA3, SIGLEC8, MID1, IL18, TNFSF10, SOAT1, EPX, CLDN1, DHTKD1, RNASE2, IL9, FFAR3, ALOX15, BDNF, IL18R1, COPD, LOC283710, IL32, IL1RL1, SLC9C2, SERPINA13P, MIR223, SPAG9, NR1I2, OGDHL, DEFB103A, FST, TNFRSF14, MIR375, EMBP1, BECN1, ABCB11, DEFB4B, BANCR, EOS, CBLL2, RSAD2, TRPV1, HBS1L, DEFB103B, CRLF2, ANO1, OXR1, SLC52A1, RHOF, TLR9, BCL11A, KLF13, CPA4, MUL1, LRRC31, CHIA, ACAD8, PANK2, MAPK8IP2, FIP1L1, SYNPO, PTGDR2, SERPINB12, SPINK5, REEP5, AGA, VCAM1, GFER, ESR2, F2RL1, FGF9, FKBP4, FKBP5, GABPA, LRRC32, GJA1, DNM1, GRM5, HIF1A, ICAM1, IFNG, IL1A, IL1B, IL5RA, ESR1, DEFB4A, TYK2, CD1D, ALOX5, ANXA5, CCND1, BID, BNIP3, CALB2, CAMP, CD44, CYP2C19, CEACAM8, CLC, CCR3, CCR8, ABCC2, COL8A2, CSF2, IL9R, IL15RA, ITGAM, CCL18, KLK6, PTGDR, PTGS2, RNASE3, S100A7, SAFB, CCL2, SGSH, KCNJ2, AGXT, SPRR3, STAT1, STC1, TFDP1, TLR3, TNFRSF4, KLK7, PRG2, PTPA, PLG, LALBA, LCT, LOX, LTC4S, SMAD2, KITLG, MIF, MMP2, MMP14, MPG, MYB, NFE2L2, SLC22A18, OSM, PRKN, SLC9A3

Drugs

Budesonide, Fluticasone propionate, Human monoclonal antibody against human interleukin 13

Budesonide, Fluticasone propionate, Human monoclonal antibody against human interleukin 13, Humanised monoclonal antibody targeting interleukin-15

Interested in hearing about new therapies?

Description

Eosinophilic esophagitis (EOE) has an incidence of approximately 1 per 10,000 people. Symptoms include difficulty feeding, failure to thrive, vomiting, epigastric or chest pain, dysphagia, and food impaction. Individuals with EOE are predominantly young males with a high rate of atopic disease, and the diagnosis is made by endoscopy and biopsy findings of isolated eosinophils in the esophagus (summary by Rothenberg et al., 2010).

Genetic Heterogeneity of Eosinophilic Esophagitis

Eosinophilic esophagitis-1 (EOE1) is associated with variation at chromosome 7q11.2. Another locus (EOE2; 613412) has been been associated with variation in the TSLP gene (607003) on chromosome 5q22.

Clinical Features

Eosinophilic esophagitis (EOE) is defined histologically by the presence of proliferative changes, including thickening of the basal epithelial layer and elongation of papillae, a minimum of 24 eosinophils per high-power field in the distal esophagus, and the absence of eosinophilia in any other intestinal segment. The disease is differentiated from reflux esophagitis (109350) on the basis of the magnitude of mucosal eosinophilia and lack of response to acid suppression (Noel et al., 2004).

In a population-based demographic study of pediatric eosinophilic esophagitis, Noel et al. (2004) identified 315 cases that met the diagnostic criteria. Further study of 103 of those patients revealed that 70% had coexisting eosinophilic involvement in the proximal esophagus; 71% were male, with a mean age of 10.5 years. Demographic analysis showed a strong familial pattern, including 3 sib pairs; and the mother of 1 of the sib pairs was also diagnosed with eosinophilic esophagitis.

Mapping

Blanchard et al. (2006) performed genomewide microarray expression analysis on esophageal tissue from 24 patients with suspected esophagitis and found that those with eosinophilic esophagitis had a striking transcript signature that was remarkably conserved across sex, age, and allergic status and was distinct from that associated with non-EOE chronic esophagitis. Within the EOE transcript signature, the gene with the greatest change was CCL26 (604697), on chromosome 7q11.2, which was induced 53-fold compared to controls. Esophageal CCL26 mRNA and protein levels strongly correlated with tissue eosinophilia and mastocytosis. Blanchard et al. (2006) genotyped a SNP (2496T-G; rs2302009) from the 3-prime UTR of the CCL26 gene in 117 patients with EOE and 225 unrelated controls and found that the G allele was overrepresented in patients with EOE compared to race/ethnicity-matched controls (p = 0.0069), and the frequency of the GG genotype was significantly higher in patients with EOE (OR 4.55, p = 0.001). Family-based transmission disequilibrium testing revealed that the G allele was preferentially transmitted from heterozygous parents to affected individuals (p = 0.0054).

Animal Model

In an experimental mouse model of EOE, mice deficient for the eotaxin receptor CCR3 (601268) were nearly completely protected from the development of esophageal eosinophilia. Blanchard et al. (2006) suggested that the CCL26 gene may be associated with susceptibility to EOE.