Potential Role of AGEs in Paediatric Allergies

Overview

Food allergy (FA) is "an adverse health effect arising from a specific immune response that occurs reproducibly" according to the 2010 National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH)-supported Guidelines for the Diagnosis and Management of Food Allergy in the United States (Boyce et al. 2010). Studies have suggested that the natural history of FA has changed during the last two decades, with a dramatic rise in the prevalence, severity of clinical manifestations, and risk of persistence into later ages, leading to an increase in hospital admissions, medical visits, treatments, and burden of care on families and to an important economic impact, with significant direct costs for the families and healthcare system (Skripak et al. 2007; McBride et al. 2012; Gupta et al. 2013). The development of FA might be influenced by genetics, environment, and genome-environment interactions, leading to immune system dysfunction, mediated at least in part by epigenetic mechanisms (Berni Canani et al. 2015; Paparo et al. 2018). Many factors have been postulated to contribute to the onset of FA. Among dietary factors, it has been hypothesized that advanced glycation endproducts (AGEs), present at high level in junk food, could be involved in FA pathogenesis. AGEs are a heterogeneous group of compounds deriving from a non-enzymatic reaction between reducing sugars and free amino groups of proteins, lipids, or nucleic acids. This reaction is also known as the Maillard or browning reaction. The formation of AGEs is a part of normal metabolism, but if excessively high levels of AGEs are reached in tissues and the circulation they can become pathogenic. AGEs are naturally present in uncooked animal-derived foods, and cooking results in the formation of new AGEs within these foods. Consumption of AGE-rich diets is associated with elevated circulating and tissue AGEs and an increase of their pro-inflammatory and pro-oxidant effects. On the other hand, restriction of AGEs prevents inflammation. AGEs not only exert their deleterious actions due to their biological properties, but also through their interaction with specific receptors (RAGE). AGEs are able to activate mast cells and induces a chronic inflammatory state that promotes a Th2 type response. The aim of this study is to evaluate the AGEs levels in FA children compared with healthy controls and subjects with other allergic diseases.

The study is designed to evaluate the AGEs concentration in allergic children compared with healthy controls and to investigate the potential role of AGEs in FA pathogenesis. First, the investigators will define subcutaneous AGEs levels in children affected by allergy, comparing to non-allergy children AGEs levels. Subsequently, the investigators will investigate the possible correlation with dietary habits and the potential effects of AGEs on gut barrier components and on non-immune and immune mechanisms in experimental models.