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Title: Markers of allergic reactions to food based on activation of mast cells and basophils
Author: Whitworth, Hilary Sian
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2011
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Confirming an allergic reaction can be a challenge, and it is difficult to assess which patients may be at risk of anaphylaxis. Our objective has been to investigate and compare potential serum markers for diagnosis of allergic reactions and predicting susceptibility to severe reactions based on mast cell and basophil activation. Levels of tryptase, chymase, carboxypeptidase and DPPI were measured in serum and saliva from 92 children (8-18 y), before, during and after diagnostic food challenge. Levels were measured using ELISAs developed and validated in our laboratory. Results were analyzed with respect to challenge outcome, and severity of reactions occurring in challenge and historically. Similar studies were performed using samples from 32 adults (17-72 y) undergoing diagnostic drug challenge. In addition, significant progress has been made towards development of new ELISA techniques for measurement of α-tryptase and ß-tryptase individually, and also for the basophil specific protease basogranulin. Serum DPPI levels were increased after moderate/severe reactions occurring in food challenge (p = 0.004). Levels of chymase in serum, and carboxypeptidase and DPPI in saliva, were elevated after positive drug challenge (p = 0.02 for all). Baseline serum levels of carboxypeptidase were predictive of severity of historical reactions to foods (p = 0.009) or drugs (p = 0.008); and concentrations of carboxypeptidase (p = 0.03) and DPPI (p = 0.02) were also associated with reaction severity in food challenge. The measurement of mast cell and basophil products should be useful not only in providing laboratory confirmation of an allergic reaction to food, but could also allow reactions to be characterized according to underlying disease mechanisms. The strong associations found between baseline levels of certain markers and the severity and nature of previous reactions raise the prospect of a test for identifying subjects who may be at particular risk of a severe reaction.
Supervisor: Walls, Andrew ; Lucas, Jane Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available