Anti-IL-5 therapy reduces mast cell and IL-9 cell numbers in pediatric patients with eosinophilic esophagitis

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• 作者：Iris M. Otani ; MD^a ; ^e ; Arjun A. Anilkumar ; BS^a ; ^e ; Robert O. Newbury ; MD^b ; ^d ; Monica Bhagat ; MD^a ; ^e ; Lisa Y. Beppu ; BS^a ; ^d ; Ranjan Dohil ; MD^c ; ^d ; David H. Broide ; MB ; ChB^a ; ^e ; Seema S. Aceves ; MD ; PhD^a ; ^d ; ^e ; ^{saceves@ucsd.edu}
• 关键词：Eosinophilic esophagitis ; pediatric ; eosinophils ; mast cells ; IL-5 ; IL-9
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：131
• 期：6
• 页码：1576-1582.e2
• 全文大小：1407 K

文摘

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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 (m>Pm>?<?.001), were significantly lower than in nonresponders after therapy (m>Pm>?<?.05), and correlated with eosinophil numbers (m>rm>?=?0.75, m>Pm>?<?.0001). Mast cells and eosinophils were found in couplets before therapy, and these were significantly decreased only in responders after anti-IL-5 (m>Pm>?<?.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 (m>Pm>?<?.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.