Bagels and LOX in patients with eosinophilic esophagitis

• Published in: Journal of allergy and clinical immunology 2019-07, Vol.144 (1), p.41-43
• Main Authors: Ben Baruch-Morgenstern, Netali, Shoda, Tetsuo, Rothenberg, Marc E.
• Format: Article
• Language: English
• Subjects: Autoimmune diseases; Biomarkers; Biopsy; Calpain; Chemokines; Chromosome 2; Collagen; Cytokines; Desmoglein 1; Endoscopy; Eosinophilic Esophagitis; Eotaxin; epithelial cells; Epithelium; Esophageal diseases; Esophagitis; Esophagus; Fibroblasts; fibrosis; Gene expression; Genotype & phenotype; Helper cells; Humans; Immunoregulation; Inflammation; Interleukin 13; Interleukin 5; Lamina propria; Leukocytes (basophilic); Leukocytes (eosinophilic); Liquid oxygen; Lymphocytes; Lymphocytes T; Lysyl oxidase; Phenotypes; Protease; Protein-Lysine 6-Oxidase; Proteinase inhibitors; Smooth muscle; Susceptibility; TGF-β; Thymus; TNF-α; Tumor Necrosis Factor-alpha
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2019.03.034

[...]after impaired barrier function mediated by a number of pathways, including lost expression of the homeostatic antiprotease serine protease inhibitor, Kazal type 7,4 the epithelium releases the pro-TH2 cytokine thymic stromal lymphopoietin, which is encoded for by the chief EoE susceptibility locus on 5q22, as well as other proinflammatory cytokines, including the alarmin IL-33.1 This initiates the TH2 inflammatory cascade by promoting secretion of TH2 cell–derived inflammatory cytokines, including IL-5 and IL-13.1 IL-13 stimulates the esophageal epithelium to secrete chemokines, such as CCL26 (eotaxin-3), and disrupts the epithelial barrier by downregulating expression of the adhesion molecule desmoglein 1 and simultaneously upregulating the protease calpain 14, which is the gene product encoded for by another chief EoE susceptibility loci (2p23).1,5 These processes promote accumulation of immune cells, predominantly eosinophils, mast cells, and basophils, that secrete TGF-β, a main cytokine in the fibrotic network.1 TGF-β is also generated by regulatory T cells that are overrepresented in the esophagi of patients with EoE.1 TGF-β acts on fibroblasts and stimulates their transdifferentiation into activated myofibroblasts that proliferate, migrate, and secrete collagen and other matrix component. Focusing on the association between gene expression and phenotype, one study showed that esophageal narrowing was associated with increased expression of CCL26, ALOX15, GRK5, CPA3, and TRIM2 in adults with EoE,6 whereas another study showed that pediatric patients with EoE with food impaction had distinct expression of regulators of esophageal motility, mast cell markers, and TH2-associated transcripts.7 Regarding endotypes, 3 clusters associate with distinct endotypes (ie, EoE endotypes 1-3) despite similar eosinophil levels.4 Interestingly, EoE endotype 3 was associated with the narrow-caliber esophagus and enriched for epithelial genes that lose expression, particularly ACPP, CITED2, CTNNAL1, EML1, FLG, GRPEL2, MT1M, PNLIPPR3, and TSPAN12. [...]up to 50% of patients might not even undergo evaluation because biopsy specimens are not deep enough to contain sufficient amount of lamina propria. [...]there is a need for better biomarkers for the fibrostenotic component of this disease.