Dataset Information

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.

SUBMITTER: Otani IM

PROVIDER: S-EPMC3699422 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Otani Iris M IM Anilkumar Arjun A AA Newbury Robert O RO Bhagat Monica M Beppu Lisa Y LY Dohil Ranjan R Broide David H DH Aceves Seema S SS

The Journal of allergy and clinical immunology 20130425 6

<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods ...[more]

PMID: 23623266

Similar Datasets

Project description:ObjectivesMast cells (MCs) are increased in eosinophilic esophagitis (EoE). Endoscopic abnormalities, symptoms, and epithelial changes can persist after treatment despite a reduction of esophageal eosinophilia. It is unknown whether this could be due to persistent MC infiltration. We aimed to determine whether patients with histologically inactive (HI) EoE (defined as <15 eosinophils per high-powered field) with persistent symptoms, endoscopic, or epithelial abnormalities after treatment have increased MCs.MethodsSecondary analysis of prospective data from 93 children with EoE undergoing post-treatment endoscopy between 2011 and 2015. Thirty-five non-EoE controls were included. Immunohistochemistry for tryptase, an MC marker, was performed on mid and distal esophageal biopsies. Total and degranulated intraepithelial MCs per high-powered field (MC/hpf) were quantified. Symptoms and endoscopic findings were recorded at time of endoscopy. MC/hpf were compared between HI-EoE and control, and among HI-EoE based on endoscopic and histologic findings, and symptoms. Nine clinical remission (CR) patients were identified, with absence of endoscopic abnormalities and symptoms.ResultsMC/hpf were increased in HI-EoE compared with control (17 ± 11 vs 8 ± 6, P < 0.0). Patients with persistent endoscopic abnormalities had increased total (20 ± 12 vs 13 ± 10, P = 0.001) and degranulated (8 ± 6 vs 5 ± 4, P = 0.002) MC/hpf, with no difference in eosinophils. MC/hpf predicted furrowing (odds ratio = 1.06, P = 0.01) and rings (odds ratio = 1.05, P = 0.03) after controlling for treatment type, proton-pump inhibitor, eosinophils, and duration of therapy. Patients with persistent basal zone hyperplasia and dilated intercellular spaces had increased MC/hpf. Eosinophils were weakly correlated with MC/hpf in the mid (r = 0.30, P < 0.001) and distal (r = 0.29, P < 0.001) esophagus. Clinical remission patients had lower MC/hpf compared with patients with persistent symptoms and/or endoscopic abnormalities.DiscussionMC density is increased in patients with endoscopic and epithelial abnormalities, as well as a few symptoms, despite resolution of esophageal eosinophilia after treatment. This association warrants further study to ascertain whether MCs play an eosinophil independent role in EoE.

Dataset Information

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

Background

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

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