Intraepithelial Lymphocyte Eotaxin-2 Expression and Perineural Mast Cell Degranulation Differentiate Allergic/Eosinophilic Colitis From Classic IBD

Torrente, Franco*; Barabino, Arrigo; Bellini, Tommaso; Murch, Simon H.

Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0000000000000432
Original Articles: Gastroenterology
Abstract

Objectives: Allergic colitis shows overlap with classic inflammatory bowel disease (IBD). Clinically, allergic colitis is associated with dysmotility and abdominal pain, and mucosal eosinophilia is characteristic. We thus aimed to characterise mucosal changes in children with allergic colitis compared with normal tissue and classic IBD, focusing on potential interaction between eosinophils and mast cells with enteric neurones.

Methods: A total of 15 children with allergic colitis, 10 with Crohn disease (CD), 10 with ulcerative colitis (UC), and 10 histologically normal controls were studied. Mucosal biopsies were stained for CD3 T cells, Ki-67, eotaxin-1, and eotaxin-2. Eotaxin-2, IgE, and tryptase were localised compared with mucosal nerves, using neuronal markers neurofilament protein, neuron-specific enolase, and nerve growth factor receptor.

Results: Overall inflammation was greater in patients with CD and UC than in patients with allergic colitis. CD3 T-cell density was increased in patients with allergic colitis, similar to that in patients with CD but lower than in patients with UC, whereas eosinophil density was higher than in all other groups. Eotaxin-1 and -2 were localised to basolateral crypt epithelium in all specimens, with eotaxin-1+ lamina propria cells found in all of the colitis groups. Eotaxin-2+ intraepithelial lymphocyte (IEL) density was significantly higher in allergic colitis specimens than in all other groups. Mast cell degranulation was strikingly increased in patients with allergic colitis (12/15) compared with that in patients with UC (1/10) and CD (0/1). Tryptase and IgE colocalised on enteric neurons in patients with allergic colitis but rarely in patients with IBD.

Conclusions: Eotaxin-2+ IELs may contribute to the periepithelial eosinophil accumulation characteristic of allergic colitis. The colocalisation of IgE and tryptase with mucosal enteric nerves is likely to promote the dysmotility and visceral hyperalgesia classically seen in allergic gastrointestinal inflammation.

Author Information

*Department of Paediatric Gastroenterology, Addenbrooke's Hospital, Cambridge, UK

Department of Paediatric Gastroenterology, Gaslini Institute, Genoa, Italy

Division of Metabolic and Vascular, Warwick Medical School, University of Warwick, Warwick, UK.

Address correspondence and reprint requests to Professor Simon Murch, Division of Metabolic and Vascular Health, Warwick Medical School, Clifford Bridge Road, Coventry CV2 2DX, UK (e-mail: s.murch@warwick.ac.uk).

Received 13 February, 2014

Accepted 2 May, 2014

The present study was supported in part by a grant to S.M. from the UK Food Standards Agency and by an unrestricted grant from the Eulie Peto Legacy.

S.M. has given lectures at meetings sponsored by the manufacturers of hypoallergenic formulae, including Danone and Mead Johnson, and has been a member of advisory panels for both companies. The other authors report no conflicts of interest.

© 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,