Antonella Cianferoni1, Melanie A Ruffner2, Ryan Guzek3, Shaobo Guan3, Terri Brown-Whitehorn1, Amanda Muir4, Jonathan M Spergel5. 1. Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Division of Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 2. Division of Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 3. Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. 4. Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 5. Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Division of Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. Electronic address: spergel@email.chop.edu.
Abstract
BACKGROUND: Eosinophilic esophagitis (EoE) is an allergic inflammatory disease that is triggered by food allergens and characterized by progressive esophageal dysfunction. Esophageal biopsy specimens are characterized by eosinophilia and expression of TH2 cytokines. OBJECTIVE: To ascertain whether TH2 cells can exist in the peripheral blood in patients with milk-induced EoE. METHODS: Peripheral blood mononuclear cells from 20 children with milk-induced EoE were collected during active EoE (EoE-A) while consuming milk and inactive EoE (EoE-I) while not consuming milk, and 8 healthy patients without EoE were used as controls. The samples were analyzed for T-cell phenotype, including intracellular cytokines before and after incubation with milk antigens and assessed by flow cytometry. RESULTS: We found a significant increase in CD4+ TH2 cells in the peripheral blood of patients with EoE-A compared with the controls. Furthermore, we observed a significant mean (SD) increase in the activation marker of CD154+ T cells (0.17% [0.047%]) in patients with EoE-A compared with control patients (0.034% [0.007%]) and EoE-I (0.025% [0.008]). These CD4+ T cells expressed significantly increase levels of TH2 cytokines (interleukins 4, 5, and 13) compared with the EoE-I and control groups. CD3+CD4+CD154+IL-5+ cells were significantly increased by milk antigens in both milk-induced EoE-A (0.050% [0.008%] to 0.079% [0.017%]) and EoE-I (0.0045% [0.002%] to 0.014% [0.008%]) compared with the controls (0.008% [0.003%] to 0.003% [0.001%]). CONCLUSION: Our findings indicate that in EoE peripheral T cells have specific activation to milk allergens.
BACKGROUND:Eosinophilic esophagitis (EoE) is an allergic inflammatory disease that is triggered by food allergens and characterized by progressive esophageal dysfunction. Esophageal biopsy specimens are characterized by eosinophilia and expression of TH2 cytokines. OBJECTIVE: To ascertain whether TH2 cells can exist in the peripheral blood in patients with milk-induced EoE. METHODS: Peripheral blood mononuclear cells from 20 children with milk-induced EoE were collected during active EoE (EoE-A) while consuming milk and inactive EoE (EoE-I) while not consuming milk, and 8 healthy patients without EoE were used as controls. The samples were analyzed for T-cell phenotype, including intracellular cytokines before and after incubation with milk antigens and assessed by flow cytometry. RESULTS: We found a significant increase in CD4+ TH2 cells in the peripheral blood of patients with EoE-A compared with the controls. Furthermore, we observed a significant mean (SD) increase in the activation marker of CD154+ T cells (0.17% [0.047%]) in patients with EoE-A compared with control patients (0.034% [0.007%]) and EoE-I (0.025% [0.008]). These CD4+ T cells expressed significantly increase levels of TH2 cytokines (interleukins 4, 5, and 13) compared with the EoE-I and control groups. CD3+CD4+CD154+IL-5+ cells were significantly increased by milk antigens in both milk-induced EoE-A (0.050% [0.008%] to 0.079% [0.017%]) and EoE-I (0.0045% [0.002%] to 0.014% [0.008%]) compared with the controls (0.008% [0.003%] to 0.003% [0.001%]). CONCLUSION: Our findings indicate that in EoE peripheral T cells have specific activation to milk allergens.
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