Drug hypersensitivity reactions are a significant public health problem with important consequences on patient health and healthcare costs. It has been reported that only a low percentage of initial cases suspected of allergy to antibiotics are finally confirmed [1, 2], and betalactam antibiotics (BLs) are the drugs most frequently involved [3, 4]. In vivo tests (skin test and drug provocation test) are often the first and only option for diagnosis, nevertheless they could be risky for patients. Thus, in vitro tests are a more convenient and safer alternative for diagnosis, however, a sensitive and specific detection of specific IgE (sIgE), crucial for in vitro allergy diagnosis, is difficult to achieve in cases of allergy to drugs due to the extremely low sIgE concentration present in patients serum [5].
The sensitivity of in vitro tests for diagnosing allergy to BLs depends, among other factors, on: (i) the similarity between the structure used in the assay as emulator of the antigenic determinant (AD) formed in vivo and the structure actually formed after the BL intake, which is related to the mechanisms involved in the allergic process, and (ii) the intensity of the detection signal (radioactivity, enzimatic proccess or fluorescence) at low concentrations of sIgE to drugs.
The general objective of this thesis is to carry out studies directed to improve current in vitro tests for diagnosing immediate allergic reactions to BLs. More specifically, by one hand, we aimed to research, from a chemical approach, the structures recognized by sIgE for cephalosporins and clavulanic acid (CLV) since there has been an increase of cases of allergy to these BLs in the last years, due to the change in prescription patterns [1]. For this purpose, structures derived from these BLs were designed and synthesized and their immunological evaluation performed using RadioAllergoSorbent Test (RAST) or Basophil Activation Test (BAT).
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