Anti–IL-5 therapy reduces mast cell and IL-9 cell numbers in pediatric patients with eosinophilic esophagitis - 30/05/13
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.
Le texte complet de cet article est disponible en PDF.Key words : Eosinophilic esophagitis, pediatric, eosinophils, mast cells, IL-5, IL-9
Abbreviations used : EoE, HES, hpf, LP
Plan
| Supported by a research grant from GlaxoSmithKline (to S.S.A.) and National Institutes of Health/National Institute of Allergy and Infectious Disease grants AI092135 (to S.S.A.), AI38425, AI70535, and AI72115 (to D.H.B.). |
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| Disclosure of potential conflict of interest: D. H. Broide has received grants from the National Institutes of Health (NIH) and the Department of Defense and has consultant arrangements with Ambit and Guidepoint. S. S. Aceves has received grants from GlaxoSmithKline and the NIH/National Institute of Allergy and Infectious Diseases, has a patent with Meritage Pharma for Oral Viscous Budesonide, has stock/stock options with Meritage Pharma, and has received travel support from the NIH as a member of the NIH CIMG Study Section. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 6
P. 1576 - juin 2013 Retour au numéro
Article précédent
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