Involvement of mast cells in eosinophilic esophagitis.
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.


CONCLUSIONS
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.
Abonia
J Pablo
JP
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Blanchard
Carine
C
Butz
Bridget Buckmeier
BB
Rainey
Heather F
HF
Collins
Margaret H
MH
Stringer
Keith
K
Putnam
Philip E
PE
Rothenberg
Marc E
ME
D000293:Adolescent; D000328:Adult; D000730:Androstadienes / Q000627:therapeutic use; D043422:Carboxypeptidases A / Q000235:genetics; D015550:Cell Degranulation; D002648:Child; D002675:Child, Preschool; D004802:Eosinophilia / Q000188:drug therapy / Q000209:etiology*; D004941:Esophagitis / Q000188:drug therapy / Q000209:etiology*; D005260:Female; D000068298:Fluticasone; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D019089:Stem Cell Factor / Q000235:genetics
D000730:Androstadienes; D019089:Stem Cell Factor; D000068298:Fluticasone; C468648:CPA3 protein, human; D043422:Carboxypeptidases A