Methods: Banked duodenal biopsies and sera from children with food allergy (FA) only or with comorbid allergic disorders (FA+CAD) were evaluated for mast cells (MCs) by flow cytometry, ImmunoCAP, immunofluorescence and immunohistochemistry and compared with non-atopic (Ctrl) individuals.
Results: Children with FA+CAD exhibited a significant increase in the accumulation of duodenal-MCs compared with patients with FA only (p 0.005, t-test) or Ctrl individuals (p 0.0004, t-test). Serum total IgE in FA+CAD patients was significantly higher compared with patients with FA only (p 0.05, unpaired t-test). Significantly increased sera IL-9 levels (but not IL-5, TNFα or IL-13) in FA or FA+CAD patients correlated with Duodenal MCs (Pearson 0.39, p 0.04) and total IgE (Pearson 0.3, p 0.03). In an atopic march model, OVA-induced AD in mice exhibit a significant accumulation of IL-9-producing mucosal mast cells (MMC9s) in the gut following repeated OVA ingestions, but not saline. Furthermore, OVA-inhalations induced MMC9-accumulation in the lungs of mice with AD and FA, but not AD alone.
Conclusions: Collectively, these results suggest that the increase of intestinal MCs frequency and sera IL-9 level in FA patients may potentiate the development of comorbid allergic disorders. Mechanistically, repeated food allergen exposures enhance the expansion of intestinal MMC9s which may contribute to the progression of the allergic response to the lungs in a murine model of atopic march.