Abstract
BackgroundThe underlying cellular mechanisms causing adverse reactions to food are complex and still not fully understood. Therefore, in this study we aimed to identify functional and/or phenotypical immune cell signatures characteristic for adult patients reporting adverse reactions to food.By mass cytometry, we performed high-dimensional profiling of peripheral blood mononuclear cells (PBMC) from adult patients reporting adverse reactions to food and healthy controls. The patients were grouped according to sIgE-positive or sIgE-negative serology to common food and inhalant allergens. Two broad antibody panels were used, allowing determination of major immune cell populations in PBMC, as well as activation status, proliferation status, and cytokine expression patterns after PMA/ionomycin-stimulation on a single cell level.ResultsBy use of data-driven algorithms, several cell populations were identified showing significantly different marker expression between the groups.Most striking was an impaired frequency and function of polyfunctional CD4+ and CD8+ T cells in patients reporting adverse reactions to food compared to the controls. Further, subpopulations of monocytes, T cells, and B cells had increased expression of functional markers such as CD371, CD69, CD25, CD28, and/or HLA-DR as well as decreased expression of CD23 in the patients. Most of the differing cell subpopulations were similarly altered in the two subgroups of patients.ConclusionOur results suggest common immune cell features for both patient subgroups reporting adverse reactions to food, and provide a basis for further studies on mechanistic and diagnostic biomarker studies in food allergy.
Highlights
The underlying cellular mechanisms causing adverse reactions to food are complex and still not fully understood
The patients reporting adverse reactions to food were assigned to two groups based on the presence or absence of any Allergen-specific immunoglobulin E (sIgE) to these food and inhalant allergens, hereafter called the IgEpos (n = 11) and IgEneg (n = 9) allergy groups
Among the patients reporting adverse reactions to food with available clinical data at the time of reporting to the Food Allergy Register, all presented mild to severe symptoms affecting mostly skin, respiratory tract, and/or gastrointestinal tract (Table 1)
Summary
The underlying cellular mechanisms causing adverse reactions to food are complex and still not fully understood. The underlying cellular mechanisms causing adverse reactions to food in subjects with a suspected food allergy but where sIgE is not detected are largely unknown [5]. In Norway, about 50% of cases reported to The Norwegian Register of Adverse Reactions to Food did not have detectable sIgE to a standard panel of 12 food allergens in serum. Most of these cases (95%) were negative for sIgE to inhalant allergens [6]. The relation between sIgE serum levels and adversity of the allergic responses varies, sIgE can occur in subjects without clinical food allergy symptoms and vice versa [10,11,12]. Other serum markers, such as IgG4 or cytokines, have been evaluated but were not validated as reliable diagnostic markers [13, 14]
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