Definition of the genetic, chemical and cellular basis of allergic drug reactions

Allergic drug reactions are important to study because they are feared by the physician as they cannot be predicted at present. However, recent advances in our laboratory on the key chemical and cellular events in drug allergy open the prospect of a more fundamental understanding of sensitization and desensitisation.

We will conduct prospective and retrospective investigations of drug allergy with respect to the in vivo chemistry of the drug, patient phenotype, patient genotype and clinical outcome. We can do this because we have established β-lactam therapy as a paradigm to characterize the dynamic relationship between drug antigenicity and allergy. Access to clinical samples collected prior to drug exposure, at the time of a reaction and during recovery provides a unique opportunity to perform interdisciplinary mechanistic studies to “complete the loop” in our understanding of β-lactam allergy from man to molecule and back again. An understanding of the factors which predict and prevent drug allergy will pave the way for both the development of safer medicines and novel diagnostic tests for the stratification of drug use. This will support patient management strategies and provide a rationale for treatment schedules for drug desensitisation.