The importance of hapten-protein complex formation in the development of drug allergy

Drug allergy is an adverse drug reaction that is immune-mediated. Immune activation can occur when drugs or haptens bind covalently to proteins and then act as antigens. The purpose of this review is to summarize the recent data on the formation of hapten-protein complexes and to assess the importance of these complexes in the generation of drug allergy.

The formation of hapten-protein complexes by drugs and their reactive metabolites has largely been investigated using model proteins such as human serum albumin. Precise identification of the structure of the hapten and the resulting modified residue(s) in the protein has been undertaken for a small number of drugs, such as p-phenylenediamine, nevirapine, carbamazepine, β-lactams and abacavir. Some progress has also been made in identifying hapten-protein complexes in the serum of patients with allergy.

Drug-specific T cells have been isolated from different patients with allergy. Formation of hapten-protein complexes, their processing and antigen presentation have been implicated in the development of drug allergy to p-phenylenediamine, sulfonamides and β-lactams. However, evidence also supports the pi mechanism of immune activation wherein drugs interact directly with immune receptors. Thus, multiple mechanisms of immune activation may occur for the same drug.