title: Anti-IL-5 therapy reduces mast cell and IL-9 cell numbers in pediatric patients with eosinophilic esophagitis.
abstract: BACKGROUND
  Eosinophilic esophagitis (EoE) is a clinicopathologic entity of increasing worldwide prevalence. IL-5 is essential for eosinophil trafficking, and anti-IL-5 therapy decreases esophageal eosinophilia. EoE is associated with prominent mast cell infiltration.
  
  
  OBJECTIVE
  We investigated whether anti-IL-5 (mepolizumab) treatment reduced esophageal mast cell accumulation in biopsy specimens from pediatric patients with EoE from a previous randomized anti-IL-5 trial.
  
  
  METHODS
  A subanalysis was completed for children treated with 0.55, 2.5, or 10 mg/kg mepolizumab monthly for 12 weeks followed by no treatment until week 24. Quantitative immunochemistry was used to assess the numbers of eosinophils, tryptase-positive mast cells, IL-9(+) cells, and mast cell-eosinophil couplets before and after treatment.
  
  
  RESULTS
  Forty-three biopsy specimens had adequate tissue for paired analysis. Forty percent of subjects responded to anti-IL-5 (defined as <15 eosinophils per high-power field [hpf] after mepolizumab therapy), and 77% of all subjects had decreased numbers of mast cells after anti-IL-5. In responders epithelial mast cell numbers decreased from 62 to 19 per hpf (P < .001), were significantly lower than in nonresponders after therapy (P < .05), and correlated with eosinophil numbers (r = 0.75, P < .0001). Mast cells and eosinophils were found in couplets before therapy, and these were significantly decreased only in responders after anti-IL-5 (P < .001). Esophageal eosinophils comprised the majority of cells that made the mast cell growth factor IL-9. IL-9(+) cell numbers decreased from 102 to 71 per hpf (P < .001) after anti-IL-5.
  
  
  CONCLUSIONS
  Pediatric patients with EoE had significantly fewer mast cells, IL-9(+) cells, and mast cell-eosinophil couplets in the esophageal epithelium after anti-IL-5 therapy. Because eosinophils were one source of IL-9, they might support esophageal mastocytosis.
authors.affiliation: Division of Allergy and Immunology, University of California, San Diego, Rady Children's Hospital, San Diego, Calif., USA.
authors.forename: Iris M
authors.initials: IM
authors.lastname: Otani
authors.forename: Arjun A
authors.initials: AA
authors.lastname: Anilkumar
authors.forename: Robert O
authors.initials: RO
authors.lastname: Newbury
authors.forename: Monica
authors.initials: M
authors.lastname: Bhagat
authors.forename: Lisa Y
authors.initials: LY
authors.lastname: Beppu
authors.forename: Ranjan
authors.initials: R
authors.lastname: Dohil
authors.forename: David H
authors.initials: DH
authors.lastname: Broide
authors.forename: Seema S
authors.initials: SS
authors.lastname: Aceves
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D004802:Eosinophilia / Q000276:immunology; D057765:Eosinophilic Esophagitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D004947:Esophagus / Q000378:metabolism; D006801:Humans; D015848:Interleukin-5 / Q000037:antagonists & inhibitors*; D016906:Interleukin-9 / Q000378:metabolism*; D008407:Mast Cells / Q000276:immunology*; D009092:Mucous Membrane / Q000378:metabolism; D053802:Tryptases / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015848:Interleukin-5; D016906:Interleukin-9; C434107:mepolizumab; D053802:Tryptases