Local allergic reaction in food-hypersensitive adults despite a lack of systemic food-specific IgE

Background: Objective tools are lacking for the diagnosis of local gastrointestinal inflammatory reactions in skin prick test (SPT)-negative and serum IgE antibody (s-IgE Ab)-negative patients with suspected food allergy. Objective: The purpose of this investigation was to evaluate the presence of eosinophils, T cells, local IgE-bearing cells, IL-4, and IFN-gamma in small intestinal biopsy specimens from adult SPT-negative/s-IgE Ab-negative patients with food allergy during symptomatic and nonsymptomatic periods. Methods: Fourteen patients with food allergy-related gastrointestinal symptoms confirmed by double-blinded, placebo-controlled food challenge (DBPCFC) were investigated. Eleven of the patients were SPT-negative and s-IgE Ab-negative. Sex- and age-matched healthy volunteers were used as controls. Duodenal biopsies were studied with immunostaining through use of a panel of mouse monoclonal antibodies specific for eosinophils, CD3, CD4, CD8, IgE, IL-4, and IFN-gamma. Results: Significant increases in numbers of MBP+ eosinophils, IgE-bearing cells, and T cells were found in the duodenal mucosa of the patients when they were symptomatic in comparison with when they were asymptomatic and in comparison with healthy controls. Numbers of IL-4(+) cells were increased and numbers of IFN-gamma+ cells were reduced in the patients when they were symptomatic in comparison with when they were asymptomatic and in comparison with the controls. There were no differences in total s-IgE levels between any of the groups. Conclusion: A significant correlation was found between the appearance of symptoms of food hypersensitivity and the duodenal presence of IgE-bearing cells, activated eosinophils, and T cells in patients with negative SPT results and negative s-IgE Ab to the offending food. We suggest that a localized IgE-mediated response caused the gastrointestinal symptoms seen in these patients.