Abstract
Peanut-specific IgE is necessary but not sufficient to elicit allergic reactions to peanut. Oral food challenge, the gold-standard for the diagnosis of peanut allergy, is indicated when tests based on the presence of IgE are equivocal; however, this is resource-intensive and carries the risk of an allergic reaction.My aims were to improve the diagnosis of peanut allergy and our understanding of the discrepancy between the presence of IgE (i.e. allergic sensitisation) and clinical allergy to peanut. Peanut allergic, peanut-sensitised but tolerant and non-sensitised non-allergic subjects were studied. Participants underwent clinical evaluation, skin prick testing, blood collection for serology and basophil and mast cell assays and oral food challenge to peanut, if clinically indicated.
The basophil activation test had 97% accuracy to diagnose peanut allergy and reduced the need for oral food challenges by 66%. It proved to be particularly useful in cases in which conventional allergy tests failed to diagnose peanut allergy. The basophil activation test also estimated the severity and the threshold of allergic reactions to peanut.
Peanut allergic patients had higher levels of peanut-specific IgE and were more likely to have IgE to peanut major allergens. Peanut-sensitised but tolerant patients showed a predominance of IgG4 over IgE. Their plasma inhibited peanut-induced activation of mast cells and basophils in vitro similar to plasma from patients submitted to peanut oral immunotherapy. The role of IgG4 in the inhibition of peanut-induced effector cell activation was confirmed by depletion of IgG4 from plasma samples of tolerant patients sensitised to major peanut allergens, which would otherwise be predictors of peanut allergy.
In conclusion, the basophil activation test reproduced in vitro the clinical phenotype of peanut-sensitised patients. Characteristics of IgE and the presence of IgG4 and possibly other blocking antibodies are two non-mutually exclusive explanations for the discrepancy between peanut allergy and sensitisation.
| Date of Award | 1 Jul 2015 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Gideon Lack (Supervisor) & Victor Turcanu (Supervisor) |