Á Arias1, A J Lucendo2, P Martínez-Fernández3,4, A M González-Castro5, M Fortea5, J González-Cervera6, J L Yagüe-Compadre7, T Mota-Huertas7, M Vicario5,8. 1. Research Unit, Hospital General La Mancha Centro, Alcázar de San Juan, Spain. 2. Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain. 3. Idipaz Research Laboratory, Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, Madrid, Spain. 4. Center for Biomedical Research on Rare Diseases (CIBERER), Instituto Carlos III, Madrid, Spain. 5. Digestive Diseases Research Unit, Laboratory of Neuro-immuno-gastroenterology, Department of Gastroenterology, Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d´Hebron, Barcelona, Spain. 6. Department of Allergy, Hospital General de Tomelloso, Tomelloso, Spain. 7. Department of Pathology, Hospital General La Mancha Centro, Alcázar de San Juan, Spain. 8. Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Spain.
Abstract
BACKGROUND: Mast cells (MCs) are abundant in the inflammatory infiltrate in eosinophilic oesophagitis (EoE), but decrease with disease remission. However, their phenotype, role in the pathophysiology of the disease, and modulation after effective dietary therapy are still unclear. OBJECTIVE: To define the phenotype of oesophageal MCs, their modulation through dietary therapy, and their association with clinical manifestations of EoE. METHODS: Oesophageal mucosal samples from 10 adult patients with EoE obtained before and after effective six-food elimination diet (SFED) therapy, as well as from 10 control subjects were analysed. Eosinophil and MC density were quantified. Gene expression of chemoattractants for eosinophils (CCL11, CCL24, and CCL26), MCs (SCF), and their receptors (CCR3 and SCFR, respectively) were assessed by means of qPCR. Gene and protein expression of specific MC proteases (CPA3, CMA, and TPSB2) were evaluated with qPCR and immunofluorescence. Clinical manifestations and atopic background were recorded. RESULTS: MC density was significantly increased in EoE compared with controls, decreasing after dietary treatment (18.6 to 1.44 cells/hpf, respectively; P < 0.001). The MCTC subtype predominated in the oesophageal mucosa (90%) in both patients with EoE and controls. Gene expression of MC-related proteases, eotaxins, and SCF were up-regulated in patients with EoE, but significantly decreased after therapy, regardless of atopic background. Epithelial peaks of MCs and eosinophils were significantly associated (ρ = 0.80) in EoE and correlated with the symptom score (ρ = 0.78). Gene expression of MC proteases and eotaxins also correlated with the symptom score (P < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: MC and its proteases seem to play a relevant role in the pathophysiology and symptoms of EoE, which can be reversed after effective dietary treatment.
BACKGROUND: Mast cells (MCs) are abundant in the inflammatory infiltrate in eosinophilic oesophagitis (EoE), but decrease with disease remission. However, their phenotype, role in the pathophysiology of the disease, and modulation after effective dietary therapy are still unclear. OBJECTIVE: To define the phenotype of oesophageal MCs, their modulation through dietary therapy, and their association with clinical manifestations of EoE. METHODS: Oesophageal mucosal samples from 10 adult patients with EoE obtained before and after effective six-food elimination diet (SFED) therapy, as well as from 10 control subjects were analysed. Eosinophil and MC density were quantified. Gene expression of chemoattractants for eosinophils (CCL11, CCL24, and CCL26), MCs (SCF), and their receptors (CCR3 and SCFR, respectively) were assessed by means of qPCR. Gene and protein expression of specific MC proteases (CPA3, CMA, and TPSB2) were evaluated with qPCR and immunofluorescence. Clinical manifestations and atopic background were recorded. RESULTS: MC density was significantly increased in EoE compared with controls, decreasing after dietary treatment (18.6 to 1.44 cells/hpf, respectively; P < 0.001). The MCTC subtype predominated in the oesophageal mucosa (90%) in both patients with EoE and controls. Gene expression of MC-related proteases, eotaxins, and SCF were up-regulated in patients with EoE, but significantly decreased after therapy, regardless of atopic background. Epithelial peaks of MCs and eosinophils were significantly associated (ρ = 0.80) in EoE and correlated with the symptom score (ρ = 0.78). Gene expression of MC proteases and eotaxins also correlated with the symptom score (P < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: MC and its proteases seem to play a relevant role in the pathophysiology and symptoms of EoE, which can be reversed after effective dietary treatment.
Authors: Lisa J Martin; James P Franciosi; Margaret H Collins; J Pablo Abonia; James J Lee; Kevin A Hommel; James W Varni; J Tommie Grotjan; Michael Eby; Hua He; Keith Marsolo; Philip E Putnam; Jose M Garza; Ajay Kaul; Ting Wen; Marc E Rothenberg Journal: J Allergy Clin Immunol Date: 2015-06 Impact factor: 10.793
Authors: Cary C Cotton; Daniel Erim; Swathi Eluri; Sarah H Palmer; Daniel J Green; W Asher Wolf; Thomas M Runge; Stephanie Wheeler; Nicholas J Shaheen; Evan S Dellon Journal: Clin Gastroenterol Hepatol Date: 2016-12-07 Impact factor: 11.382