ABSTRACT
Food allergies have become a health concern worldwide. Around 6% to 10% of children are allergic to cow's milk proteins. We have previously characterized colorectal polyps in patients sensitized to food allergens. These polyps are classified as inflammatory and present a type 2 environment, with elevated interleukin (IL)-13 and IL-4, and are a site of immunoglobulin E synthesis. In this study, we characterized and isolated cow's milk protein-specific T cell lines and T cell clones from the lamina propria of polyps from patients sensitized to these proteins. Isolated T cells responded to cow's milk proteins similarly to peripheral blood T cells, showing antigen-specific cell proliferation and Th2 cytokines release in vitro. T cell clones obtained were all CD4+ T cells and expressed the membrane TCRαß receptor and secreted higher IL-4, IL-5, and IL-13 amounts than unstimulated cells, whereas interferon γ secretion remained unchanged. Remarkably, the gut homing chemokine receptor CCR9 was augmented in cow's milk-specific peripheral and lamina propria T cells, and CCL25 was found to be expressed in the inflammatory polyp tissue and not in the adjacent mucosa. In conclusion, we isolated and characterized cow's milk-specific lamina propria CD4+ Th2 cells from colonic inflammatory polyps. CCR9 expression on these cells, along with increase secretion of CCL25 in the polyp, favors recruitment and cow's milk-specific allergic response within the inflammatory polyp tissue. Our findings may be critical to understand the underlying mechanism that promotes immunoglobulin E synthesis in the colon of cow's milk proteins allergic patients, contributing to the development of novel T cell-targeted immunotherapies.
Subject(s)
Food Hypersensitivity , Milk Hypersensitivity , Animals , Female , Child , Humans , Cattle , Infant , Th2 Cells/metabolism , Interleukin-4 , Interleukin-13/metabolism , Allergens , Milk Proteins , Colon , Immunoglobulin EABSTRACT
Several inflammatory processes of the bowel are characterized by an accumulation of eosinophils at inflammation sites. The mechanisms that govern mucosal infiltration with eosinophils are not fully understood. In this work, we studied the colorectal polyp-confined tissue containing eosinophils and we hypothesized that intestinal epithelial cells are the cell source of eotaxin-3 or CCL26, a potent chemoattractant for eosinophils. We analyzed colorectal polyps (n=50) from pediatric patients with rectal bleeding by H&E staining and eosin staining, and different pro-inflammatory cytokines were assessed by RT-qPCR and ELISA. IgE and CCL26 were investigated by RT-qPCR, ELISA and confocal microscopy. Finally, the intracellular signaling pathway that mediates the CCL26 production was analyzed using a kinase array and immunoblotting in human intestinal Caco-2 cell line. We found a dense cell agglomeration within the polyps, with a significantly higher frequency of eosinophils than in control adjacent tissue. IL-4 and IL-13 were significantly up-regulated in polyps and CCL26 was elevated in the epithelial compartment. Experiments with Caco-2 cells showed that the type-2 cytokine IL-13 increased STAT3 and STAT6 phosphorylation and eotaxin-3 secretion. The addition of the blocking antibody Dupilumab or the inhibitor Ruxolitinib to the cytokine-stimulated Caco-2 cells diminished the CCL26 secretion to basal levels in a dose-dependent manner. In conclusion, our findings demonstrate a high frequency of eosinophils, and elevated levels of type-2 cytokines and eotaxin-3 in the inflammatory stroma of colorectal polyps from pediatric patients. Polyp epithelial cells showed to be the main cell source of CCL26, and IL-13 was the main trigger of this chemokine through the activation of the STAT3/STAT6/JAK1-2 pathway. We suggest that the epithelial compartment actively participates in the recruitment of eosinophils to the colonic polyp-confined inflammatory environment.
Subject(s)
Colonic Polyps , Interleukin-13 , Caco-2 Cells , Chemokine CCL26 , Chemokines, CC/metabolism , Child , Cytokines/metabolism , Eosinophils/metabolism , Epithelial Cells/metabolism , Humans , Interleukin-13/metabolismABSTRACT
La ingestión de cuerpo extraño (CE) es la segunda causa de endoscopia de urgencia después de la hemorragia de vías digestivas; es un problema frecuente en la población pediátrica. Los niños pueden ingerir cualquier tipo de objeto, la mayoría de los cuales pueden pasar sin inconvenientes por el tracto gastrointestinal. No obstante, algunos pueden poner en riesgo la vida o acarrear complicaciones
Foreign body ingestion is the second cause of emergency endoscopy after bleeding from the digestive tract; It is a frequent problem in the pediatric population. Children can ingest any type of object, most of which can pass without inconvenience through the gastrointestinal tract; however, some can be life-threatening or complicating
Subject(s)
Child , Endoscopy, Gastrointestinal , Esophagus , Foreign-Body MigrationABSTRACT
Objetivo: Evaluar las características epidemiológicas de un grupo de pacientes pediátricos con esofagitis eosinofílica (EEo) y las modalidades de tratamiento empleadas en Latinoamérica. Pacientes y métodos: Estudio multicéntrico, observacional, transversal. Se aplicó una encuesta a 36 Centros de Gastroenterología y Endoscopia Pediátrica de 10 países latinoamericanos con la finalidad de obtener información socio-demográfica y datos sobre el tratamiento utilizado para el manejo de los casos evaluados durante el periodo 2014-2016. Resultados: 372 casos de EEo pediátrica fueron evaluados durante el periodo 2014-2016 y 108 casos (29%) correspondieron al trimestre Abril-Junio 2016. 46,72% de los casos pertenecían al grupo de edad escolar y 71,8% consultaron por disfagia. 87,2% de los pacientes fueron manejados con dieta, 55,3% esteroides deglutidos (12,8% en monoterapia) y 6% recibió montelukast. No hubo reporte de pacientes en terapia con agentes biológicos. Conclusiones: los resultados sugieren un predominio del sexo masculino con una mayor incidencia de la enfermedad en la edad escolar y la adolescencia. Las manifestaciones clínicas más frecuentes son disfagia, vómitos y síntomas de reflujo gastroesofágico. El tratamiento más indicado por los especialistas en América Latina es la dieta seguido del uso de esteroides deglutidos. Los IBP también son ampliamente utilizados como terapia coadyuvante. Un estudio de prevalencia a nivel continental es necesario para evaluar el comportamiento de la enfermedad en diferentes regiones de América Latina.
Aims: To evaluate epidemiological features of pediatric patients with eosinophilic esophagitis in Latinamerica and therapeutical options indicated by pediatric gastroenterologists in our continent. Patients and methods: multicenter, observational, transversal study. 36 Centers of Pediatric Gastroenterology and Endoscopy from 10 latinamerican countries participated giving clinical and sociodemographic information about pediatric patients with EoE diagnosed and treated during the last two years (study period). Results: 372 cases of pediatric EoE were evaluated during period 2014-2016 (108 cases were evaluated during trimester April-June 2016). 46,72% of cases were school age children, with dysphagia been the main clinical symptom in 71,8% of patients. 87,2% of patients received diet as a main indication of treatment, 55,3% received swallowed steroids (12,8% as monotherapy) and 6% were treated with montelukast among others. There were no reports of patients under treatment with biological drugs. Conclusions: epidemiological features of our study group suggest a higher prevalence of pediatric EoE in male school age children and adolescents. Most frecuent clinical symptoms are dysphagia, vomiting and gastroesophageal reflux symptoms. Treatment is based mainly on diet and swallowed steroids. A continental prevalence study is necessary to evaluate the behavior of the disease in different regions of Latinamerica.
ABSTRACT
During the last twenty years Eosinophilic Esophagitis has become one the most important causes of esophageal disfunction in children, food impactation in adolescents and young adults, therapeutic failure in patients with gastroesophageal reflux disease (GERD) and the most frecuent eosinophilic disease of the gastrointestinal tract. We present recommendations for the diagnosis and treatment of the disease based in a systematic review of the literature.
