Prerana Williamson1, James Proudfoot2, Armen Gharibans3, Lucas Dohil4, Robert Newbury5, Jacqueline Barsamian6, Maheen Hassan1, Renee Rawson4, David Katzka7, Richard Kurten8, Ranjan Dohil1, Hayat Mousa1, Seema Aceves9. 1. Department of Pediatrics, University of California, San Diego, California; Division of Pediatric Gastroenterology, Rady Children's Hospital, San Diego, California; Rady Children's Hospital, San Diego, California. 2. Altman Clinical and Translational Research Institute, University of California, San Diego, California. 3. Rady Children's Hospital, San Diego, California; Department of Surgery, University of Auckland, Auckland, New Zealand; Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand. 4. Department of Pediatrics, University of California, San Diego, California; Division of Allergy and Immunology, University of California San Diego, San Diego, California. 5. Department of Pediatrics, University of California, San Diego, California; Rady Children's Hospital, San Diego, California; Department of Pathology, University of California San Diego, San Diego, California. 6. Rady Children's Hospital, San Diego, California. 7. Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota; Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. 8. Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas. 9. Rady Children's Hospital, San Diego, California; Division of Allergy and Immunology, University of California San Diego, San Diego, California; Department of Medicine, University of California San Diego, San Diego, California. Electronic address: saceves@health.ucsd.edu.
Abstract
BACKGROUND & AIMS: Esophageal remodeling in eosinophilic esophagitis (EoE) can lead to esophageal rigidity with eventual luminal compromise and stenoses. Gauging esophageal functional alterations in EoE is challenging. An epithelial marker of functional remodeling would impact EoE management. METHODS: Esophageal biopsy specimens from children with and without EoE and primary human esophageal epithelial cells were used for PAI-1 immunohistochemistry, and cell proliferation experiments. PAI-1 immunostaining and basal cell hyperplasia were assessed in the context of concurrently obtained esophageal compliance measures on endoscopic functional lumen imaging probe (EndoFLIP). RESULTS: EndoFLIPs were performed in 45 children (32 with and 13 without EoE). Epithelial PAI-1 was increased in patients with active EoE versus inactive or control patients (P < .01). Esophageal compliance was lower in EoE patients versus controls, particularly in the proximal esophagus (P < .001). Proximal compliance was the strongest predictor of EoE (AUROC 0.88, 95% CI 0.77, 0.98) with esophageal compliance of less than 2.6%mL/mmHg demonstrating 82% sensitivity and 84% specificity for EoE. PAI-1 inhibition significantly diminished esophageal epithelial cell proliferation, suggesting PAI-1 could trigger basal cell hyperplasia. A composite mid-esophageal BZH + PAI-1 score was the strongest predictor of altered compliance (P = .02, AUROC 0.89 (95% CI 0.80, 0.99). CONCLUSIONS: PAI-1 is significantly elevated in pediatric EoE and distinguishes altered compliance in children. PAI-1 may be a novel disease marker and therapeutic target.
BACKGROUND & AIMS: Esophageal remodeling in eosinophilic esophagitis (EoE) can lead to esophageal rigidity with eventual luminal compromise and stenoses. Gauging esophageal functional alterations in EoE is challenging. An epithelial marker of functional remodeling would impact EoE management. METHODS: Esophageal biopsy specimens from children with and without EoE and primary human esophageal epithelial cells were used for PAI-1 immunohistochemistry, and cell proliferation experiments. PAI-1 immunostaining and basal cell hyperplasia were assessed in the context of concurrently obtained esophageal compliance measures on endoscopic functional lumen imaging probe (EndoFLIP). RESULTS: EndoFLIPs were performed in 45 children (32 with and 13 without EoE). Epithelial PAI-1 was increased in patients with active EoE versus inactive or control patients (P < .01). Esophageal compliance was lower in EoE patients versus controls, particularly in the proximal esophagus (P < .001). Proximal compliance was the strongest predictor of EoE (AUROC 0.88, 95% CI 0.77, 0.98) with esophageal compliance of less than 2.6%mL/mmHg demonstrating 82% sensitivity and 84% specificity for EoE. PAI-1 inhibition significantly diminished esophageal epithelial cell proliferation, suggesting PAI-1 could trigger basal cell hyperplasia. A composite mid-esophageal BZH + PAI-1 score was the strongest predictor of altered compliance (P = .02, AUROC 0.89 (95% CI 0.80, 0.99). CONCLUSIONS: PAI-1 is significantly elevated in pediatric EoE and distinguishes altered compliance in children. PAI-1 may be a novel disease marker and therapeutic target.
Authors: Calies Menard-Katcher; Alain J Benitez; Zhaoxing Pan; Faria N Ahmed; Benjamin J Wilkins; Kelley E Capocelli; Chris A Liacouras; Ritu Verma; Jonathan M Spergel; Glenn T Furuta; Amanda B Muir Journal: Am J Gastroenterol Date: 2017-05-16 Impact factor: 10.864
Authors: S S Aceves; R O Newbury; D Chen; J Mueller; R Dohil; H Hoffman; J F Bastian; D H Broide Journal: Allergy Date: 2009-10-01 Impact factor: 13.146