Sphingosine-1-phosphate as a biomarker for disease severity of food adverse reaction

Food allergies represent an increasing health concern in the industrialized countries and especially affect pediatric patients. In this population adverse reactions against food compounds can lead to anaphylactic reactions. Despite substantial research efforts, clinical markers predicting disease severity and symptoms are missing to date. Recent studies have revealed that sphingolipids, especially sphingosine-1-phosphate (S1P), play an essential role in allergy. It was reported that asthmatic patients have higher S1P levels in bronchiallavage fluids after allergen challenge. First experimental studies revealed a correlation of S1P and the outcome of anaphylaxis. Furthermore, we have shown in our recent mouse study that S1P homeostasis is pivotal for food allergy induction and effector cell response. Therefore, it is the aim of the presented pilot project to evaluate whether S1P serum titers are altered in food allergic children and if the S1P levels correlate with the outcome of anaphylaxis during double blind placebo controlled food challenges (DBPCFCs).

Specific lipids, the so-called sphingolipids, are not only essential constituents of cell membranes, but also contribute to the development and progression of immune mediated diseases such as allergies. Especially the sphingolipid sphingosine-1-phosphate (S1P) has major impact due to its immune cell activating and immune cell recruiting function. We have reported previously that S1P influences the development of food allergy. However, it was shown that S1P additionally contributes to recovery from severe allergic reactions, the anaphylactic shock. Based on this knowledge we have recruited children with suspected food allergies undergoing diagnostic oral provocation tests with potential allergen triggers in the first part of the project. S1P levels were measured in childrens blood samples and compared with routine parameters in current use to determine severe allergic reactions such as tryptase and histamine. Our data indicated children with milder symptoms after food provocation to have higher blood S1P levels before food challenges than children showing an anaphylactic response. This correlation was neither observed for histamine nor for tryptase before provocations. Therefore, modulation of these lipid levels in blood might be a promising approach to impede severe allergic reactions. Using intestinal epithelial cells, we were additionally able to demonstrate that upon S1P stimulation, cells form a tight epithelial barrier, resulting in a reduced epithelial permeability. As the mucosal barrier function is impaired in situations of severe allergic reactions, these results provide possible explanations how these lipids might counteract anaphylaxis. For the genetically mediated disease cystic fibrosis, we have demonstrated that adult cystic fibrosis patients have lower S1P levels than healthy controls. In adulthood after lung transplantation especially the gastrointestinal tract is affected, and gastrointestinal complaints are more frequently observed in patients with low S1P levels. Thus, our data indicate that modulation of S1P blood levels might be a promising treatment option in immunologically medicated diseases such as allergies and in chronic inflammations, especially when the gastrointestinal tract is affected.