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Comprehensive metabolomic analysis of peanut-induced anaphylaxis in a murine model

Chalcraft, KR;Kong, J;Waserman, S;Jordana, M;McCarry, BE;

Acute anaphylaxis caused by food allergy is a potentially life-threatening allergic reaction that results in thousands of hospitalizations in North America every year. There are currently no effective means of treatment for anaphylaxis beyond the administration of epinephrine which is only given after a reaction has already started. Further- more, knowledge regarding the underlying physico-chemi- cal basis of anaphylaxis is largely incomplete. Arguably, the study of anaphylaxis by comprehensive metabolomics offers a unique opportunity to study this phenomenon due to its ability to provide a snap-shot of the chemical state of a subject experiencing anaphylaxis encompassing both endogenous and exogenous factors including dietary and environmental effects. In this study, we sought to apply a comprehensive metabolomics approach using liquid chro- matographymass spectrometry to a murine model of pea- nut-induced anaphylaxis. The results of this study revealed that the metabolomic profiles of mice experiencing peanut- induced anaphylaxis followed a distinct pattern that mirrors the time-stage of anaphylaxis being experienced. Direct comparison of anaphylactic mice to time-matched control mice showed that the metabolomic profiles changed con- siderably as the anaphylactic reaction progressed. This comparison also revealed changes in both known biomarkers of anaphylaxis such as histamine and methylhistamine as well as a suite of metabolites chemically similar to known anaphylaxis mediators but whose biological functions are not well understood. These metabolites include a number of phospholipids such as a variety of phosphatidylcholines and lyso-phosphatidylcholines that may be of interest for further investigation regarding their potential as anaphylaxis mediators or chemical precursors to mediators.