Insights into the Mechanism of Idiosyncratic Drug-induced Agranulocytosis

Many drugs are known to cause idiosyncratic drug-induced agranulocytosis, although the mechanism is not well understood. This adverse event is suspected to be the result of the drugâ s reactive metabolite binding to endogenous proteins and creating a foreign body capable of eliciting an immune response. In particular, clozapine has been shown to form reactive metabolites by neutrophil myeloperoxidase (MPO). These studies set out to further characterize MPOâ s role in bioactivating drugs that cause idiosyncratic drug-induced agranulocytosis and to characterize the immune response seen due to clozapine. Overall this work further characterized the early immune response seen due to clozapine treatment using in vitro and in vivo methods. Through this work we have a better understanding of the immune response that may lead to clozapine-induced agranulocytosis. Understanding the clozapine-induced immune response may provide avenues for early detection of clozapine-induced agranulocytosis and ultimately limit the magnitude of this adverse event.M.Sc