Food allergy (FA) has become a public health concern, affecting a sizeable segment of the population. Despite the alarming increase in its prevalence, efforts to contain the food allergy epidemic have been stymied by the limited understanding of disease pathogenesis and the dearth of biomarkers predictive of disease onset, its course and outcome. To that end, our preliminary studies in a mouse model of FA using untargeted metabolomic profiling revealed a dysregulation in carbohydrate metabolism, which led us to hypothesize a role for the adipokine resistin like molecule beta (RELM?) in the pathogenesis of FA. RELM? transcripts were increased in the gut of FA-prone Il4raF709 mice, together with increased serum levels of RELM? but not the related adopkine RELM?. Deletion in these mice of the RELM?-encoding gene, Retnlb, protected them from FA. Importantly, RELM? levels were strongly elevated in sera of children with FA as compared to asthmatics and to healthy controls. According, we hypothesize that subjects with FA will manifest a metabolomic signature in their serum reflective of disease activity which, together with serum RELM?, will be predictive of disease attributes such as severity and outcome.
In Aim 1, we will identify the mechanisms by which RELM? promotes FA in Il4raF709 mice and its contribution to the metabolomic signature in these mice.
In Aim 2, we will validate the role of RELM? as a biomarker for human FA by extending serum RELM? analysis to other comparison groups ? including atopic dermatitis and eosinophilic esophagitis, and to identify disease attributes of FA that correlate with RELM? elevation.
In Aim 3, we will establish the metabolomic profiles associated with FA in children using untargeted metabolomics and relate to measures of disease outcome. Our proposed studies will validate novel biomarkers of food allergy, including metabolomics markers and RELM?, and elucidate the role of RELM? and metabolomic abnormalities in disease pathogenesis.
Food allergy is a serious and rapidly growing public health concern. The lack of a thorough understanding of disease mechanisms has adversely affected the development of highly effective therapies. Our proposed studies utilize an approach called metabolomic profiling to identify a set of novel disease markers found in the blood of food-allergic but not healthy children. We also propose to investigate the role in these disease markers of candidate protein called Resistin like molecule beta that was found to be elevated in food allergic children and which may act to promote food allergy. Our studies offer the possibility of better diagnosis and prediction of disease outcome in food allergy as well as potential intervention strategies in disease therapy.
