New Advances in the Study of IgE Drug Recognition

Allergic drug reactions are currently a major public health problem affecting patient health and increasing healthcare costs. They are caused by interactions between a drug and the human immune system and result in symptoms ranging from urticaria or angioedema to those more serious such as anaphylaxis or anaphylactic shock. The most commonly accepted mechanism for immunological activation is based on the hapten hypothesis. Drugs are low molecular weight substances that cannot cause an immune response on their own. However, they can act as haptens and form covalent adducts with proteins. The resulting hapten-carrier (drug-protein) conjugate can induce the production of IgE antibodies or T cells. An epitope, or antigenic determinant, is the part of the drug-protein antigen that is specifically recognized by the immune system. This may involve not only the drug derivative but also part of the carrier protein. Understanding the way in which drugs are metabolized after protein conjugation is vital in order to make progresses in the diagnosis of clinical allergy. In this review, recent advances in the identification of the chemical structures of antigenic determinants involved in immediate allergic reactions to drugs are presented. We have focused on drugs that most commonly elicit these reactions: betalactam and quinolone antibiotics and the non-steroidal anti-inflamatory drug pyrazolone. This will be discussed from a chemical point of view, relating our understanding of drug structure, chemical reactivity and immune recognition.