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.
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.
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.
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.