BACKGROUND: Eosinophilic esophagitis (EE) is an emerging disorder with poorly understood pathogenesis. OBJECTIVE: Whereas prior studies have primarily focused on the role of eosinophils in disease diagnosis and pathogenesis, this study investigates the involvement of mast cells. METHODS: Total and degranulated mast cell counts were correlated to microarray and RT-PCR data to generate transcriptome expression profiles related to mast cell number and degranulation in patients with EE and healthy control subjects. RESULTS: Esophageal mastocytosis and mast cell degranulation were readily apparent in patients with EE compared with control subjects (P < .01), as assessed by staining for total mast cells and the presence of extracellular mast cell tryptase (P < .01). Microarray analysis revealed that mast cell levels correlated with the dysregulation of 0.8% (301 genes) of the genome, which was partially distinct from the genes that correlated with tissue eosinophilia. The expression of transcripts for the mast cell proteases carboxypeptidase A3 and tryptase, but not chymase, correlated with mast cell levels and distinguished patients with EE from control subjects. Suprabasilar mast cell counts (P < .01) and degranulation (P < .01) were proportional with KIT ligand mRNA expression. Treatment of patients with EE with swallowed fluticasone propionate normalized levels of mast cells and the mast cell-related transcriptome in responder patients. CONCLUSION: Herein we have identified local mastocytosis and mast cell degranulation in the esophagi of patients with EE; identified an esophageal mast cell-associated transcriptome that is significantly divergent from the eosinophil-associated transcriptome, with carboxypeptidase A3 mRNA levels serving as the best mast cell surrogate marker; and provided evidence for the involvement of KIT ligand in the pathogenesis of EE. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
BACKGROUND:Eosinophilic esophagitis (EE) is an emerging disorder with poorly understood pathogenesis. OBJECTIVE: Whereas prior studies have primarily focused on the role of eosinophils in disease diagnosis and pathogenesis, this study investigates the involvement of mast cells. METHODS: Total and degranulated mast cell counts were correlated to microarray and RT-PCR data to generate transcriptome expression profiles related to mast cell number and degranulation in patients with EE and healthy control subjects. RESULTS:Esophageal mastocytosis and mast cell degranulation were readily apparent in patients with EE compared with control subjects (P < .01), as assessed by staining for total mast cells and the presence of extracellular mast cell tryptase (P < .01). Microarray analysis revealed that mast cell levels correlated with the dysregulation of 0.8% (301 genes) of the genome, which was partially distinct from the genes that correlated with tissue eosinophilia. The expression of transcripts for the mast cell proteases carboxypeptidase A3 and tryptase, but not chymase, correlated with mast cell levels and distinguished patients with EE from control subjects. Suprabasilar mast cell counts (P < .01) and degranulation (P < .01) were proportional with KIT ligand mRNA expression. Treatment of patients with EE with swallowed fluticasone propionate normalized levels of mast cells and the mast cell-related transcriptome in responder patients. CONCLUSION: Herein we have identified local mastocytosis and mast cell degranulation in the esophagi of patients with EE; identified an esophageal mast cell-associated transcriptome that is significantly divergent from the eosinophil-associated transcriptome, with carboxypeptidase A3 mRNA levels serving as the best mast cell surrogate marker; and provided evidence for the involvement of KIT ligand in the pathogenesis of EE. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Authors: Jonathan M Spergel; Terri Brown-Whitehorn; Janet L Beausoleil; Michele Shuker; Chris A Liacouras Journal: J Allergy Clin Immunol Date: 2007-02 Impact factor: 10.793
Authors: Seema S Aceves; Robert O Newbury; Ranjan Dohil; John F Bastian; David H Broide Journal: J Allergy Clin Immunol Date: 2007-01 Impact factor: 10.793
Authors: Amal H Assa'ad; Philip E Putnam; Margaret H Collins; Rachel M Akers; Sean C Jameson; Cassie L Kirby; Bridget K Buckmeier; Jennifer Z Bullock; Ann R Collier; Michael R Konikoff; Richard J Noel; Jesus R Guajardo; Marc E Rothenberg Journal: J Allergy Clin Immunol Date: 2007-01-25 Impact factor: 10.793
Authors: Marc E Rothenberg; Jonathan M Spergel; Joseph D Sherrill; Kiran Annaiah; Lisa J Martin; Antonella Cianferoni; Laura Gober; Cecilia Kim; Joseph Glessner; Edward Frackelton; Kelly Thomas; Carine Blanchard; Chris Liacouras; Ritu Verma; Seema Aceves; Margaret H Collins; Terri Brown-Whitehorn; Phil E Putnam; James P Franciosi; Rosetta M Chiavacci; Struan F A Grant; J Pablo Abonia; Patrick M A Sleiman; Hakon Hakonarson Journal: Nat Genet Date: 2010-03-07 Impact factor: 38.330
Authors: Michael R Konikoff; Richard J Noel; Carine Blanchard; Cassie Kirby; Sean C Jameson; Bridget K Buckmeier; Rachel Akers; Mitchell B Cohen; Margaret H Collins; Amal H Assa'ad; Seema S Aceves; Philip E Putnam; Marc E Rothenberg Journal: Gastroenterology Date: 2006-08-16 Impact factor: 22.682
Authors: Seema S Aceves; Robert O Newbury; Ranjan Dohil; Jeffrey Schwimmer; John F Bastian Journal: J Clin Gastroenterol Date: 2007-03 Impact factor: 3.062
Authors: Alfredo J Lucendo; Marta Navarro; Carmen Comas; Juan M Pascual; Emilio Burgos; Luis Santamaría; Javier Larrauri Journal: Am J Surg Pathol Date: 2007-04 Impact factor: 6.394
Authors: Tetsuji Takabayashi; Atsushi Kato; Anju T Peters; Lydia A Suh; Roderick Carter; James Norton; Leslie C Grammer; Bruce K Tan; Rakesh K Chandra; David B Conley; Robert C Kern; Shigeharu Fujieda; Robert P Schleimer Journal: J Allergy Clin Immunol Date: 2012-04-24 Impact factor: 10.793
Authors: Evan S Dellon; Xiaoxin Chen; C Ryan Miller; Karen J Fritchie; Tara C Rubinas; John T Woosley; Nicholas J Shaheen Journal: Am J Gastroenterol Date: 2010-10-26 Impact factor: 10.864
Authors: Ashmi Doshi; Rebecca Khamishon; Renee Rawson; Loan Duong; Lucas Dohil; Stephen J Myers; Braxton Bell; Ranjan Dohil; Robert O Newbury; Kim E Barrett; Richard C Kurten; Seema S Aceves Journal: J Pediatr Gastroenterol Nutr Date: 2019-02 Impact factor: 2.839