Finally, several promising therapeutic agents (e.g., sialic acid-binding immunoglobulin-like lectin 8 antibodies, the transforming growth factor-β1 signal blocker losartan, CC chemokine receptor type 3 antagonists, thymic stromal lymphopoietin antibodies, antibodies targeting the α4β7 integrin, anti-interleukin-9 antibodies, and anti-interleukin-15 antibodies) that target specific molecules or cells implicated in the pathogenesis of EoE are proposed.
Identified genetic variants in FLG, DSG1, CAPN14, SPINK5, and SPINK7 link EoE to epithelial barrier dysfunction, whereas variants in CCL26, POSTN, and TSLP associate EoE with T helper type 2-mediated immunity.
We discuss areas of the genome associated with both EoE and other allergic diseases, including the well-studied variants encoding thymic stromal lymphopoietin and calpain 14, among other "atopic" regions.
We tested for gene-environment interaction between EoE-predisposing polymorphisms (within TSLP, LOC283710/KLF13, CAPN14, CCL26, and TGFB) and implicated early-life factors (antibiotic use in infancy, cesarean delivery, breast-feeding, neonatal intensive care unit [NICU] admission, and absence of pets in the home).
In particular, the main EoE disease susceptibility loci at 2p23 and 5p22 encode for gene products that are produced by the esophageal epithelium: the intracellular protease calpain 14 and thymic stromal lymphopoietin, respectively.
Thymic stromal lymphopoietin (TSLP), which has been studied in various allergic diseases such as asthma, atopic dermatitis (AD) and eosinophilic esophagitis (EoE), has been less considered to be involved in IBDs.
Specific disease-risk loci that are shared between EoE and other allergic diseases (TSLP, LRRC32) or unique to EoE (CAPN14), as well as Mendellian Disorders associated with EoE, will be reviewed in the context of the insight that they provide into the molecular pathoetiology of EoE.
Treatment with TSLP reconstituted hallmark features of EoE in TRAIL(-/-) mice and recombinant TRAIL induced esophageal TSLP expression in vivo in the absence of allergen.
For TSLP-WDR36 region, rs3806932 (G allele protective against eosinophilic esophagitis) and rs2416257 (A allele associated with lower eosinophil counts and protective against asthma) were correlated with decreased expression of TSLP in BAL (P = 7.9 × 10(-11) and 5.4 × 10(-4) , respectively) and BEC, but not WDR36.
Genetic studies have shown that EoE is associated with single nucleotide polymorphism on genes, which are released by the epithelium and important in atopic inflammation such as thymic stromal lymphopoietin located (TSLP) close to the Th2 cytokine cluster [interleukin (IL)-4, IL-5, IL-13] on chromosome 5q22, Calpain 14, EMSY, and Eotaxin3.
TSLP genetic variants and its dysregulated expression have been linked to atopic diseases such as atopic dermatitis, asthma, allergic rhinitis and eosinophilic esophagitis.
A nonsynonymous polymorphism in the thymic stromal lymphopoietin receptor (TSLPR) gene on Xp22.3 and Yp11.3 was significantly associated with disease only in male patients with EE.
We discuss areas of the genome associated with both EoE and other allergic diseases, including the well-studied variants encoding thymic stromal lymphopoietin and calpain 14, among other "atopic" regions.
Eosinophilic esophagitis is an emerging disease that is distinguished from gastroesophageal reflux disease by the expression of a unique esophageal transcriptome and the interplay of early life environmental factors with distinct genetic susceptibility elements at 5q22 (TSLP) and 2p23 (CAPN14).
The interplay of gene (CAPN14 and LOC283710/KLF13) and early-life environment factors (breast-feeding and NICU admission) might contribute to EoE susceptibility.
In particular, the main EoE disease susceptibility loci at 2p23 and 5p22 encode for gene products that are produced by the esophageal epithelium: the intracellular protease calpain 14 and thymic stromal lymphopoietin, respectively.
Thus CAPN14 is a unique protease with distinct tissue-specific expression and function in patients with EoE and is a potential therapeutic target for EoE and related eosinophilic and allergic diseases.
Specific disease-risk loci that are shared between EoE and other allergic diseases (TSLP, LRRC32) or unique to EoE (CAPN14), as well as Mendellian Disorders associated with EoE, will be reviewed in the context of the insight that they provide into the molecular pathoetiology of EoE.
Genetic studies have shown that EoE is associated with single nucleotide polymorphism on genes, which are released by the epithelium and important in atopic inflammation such as thymic stromal lymphopoietin located (TSLP) close to the Th2 cytokine cluster [interleukin (IL)-4, IL-5, IL-13] on chromosome 5q22, Calpain 14, EMSY, and Eotaxin3.