Specificity of drug-induced immune cytopenias

What conclusions can be drawn concerning specificity of drug-induced immune reactions? We have seen that specificity of these reactions depends on several molecular features including the chemical nature of the drug, specific domains of particular membrane components, and as yet unidentified characteristics that determine selectivity for one or more cell types. This latter property does not seem to be related to shared membrane components because, for example, Rh antigens on RBCs, the peptide tail region of GPIb alpha on platelets, and the 85-kd GP on neutrophils are clearly not part of the same molecules. From multiple studies of quinine/quinidine-dependent and nomifensine-dependent antibody interactions with platelets and RBCs, respectively, we can conclude that these particular reactions are a function of specific features of the drug molecules and specific domains of various membrane glycoproteins. These characteristics strongly argue that the hypervariable regions of drug-dependent, platelet and RBC antibodies recognize simultaneously a specific domain of the membrane GP and a specific configuration of the drug molecule. If this is true, then it follows that together a specific domain of the cell membrane component plus the drug define an antigenic determinant or epitope for attachment of certain drug-dependent antibodies. We have also seen that some drug-dependent antibodies preferentially react with the drug alone when it is attached to cell membranes (eg, penicillin-dependent antibodies reacting with penicillin-coated RBCs or platelets). Some drugs elicit antibodies that react at specific sites on the cell membrane independently of drug (eg, nomifensine and the Rh antigens (E) or quinidine and platelet GPV). These three concepts of antibody specificity induced by drugs are presented in Fig 6, using RBCs as an example. Despite major advances in understanding drug-induced immune reactions during the past four decades, several important questions remain to be answered. For example, why are platelets involved more frequently than other cells of the circulation in these types of reactions? Why do some individuals develop drug-induced immune cytopenias that are specific for a single cell type, whereas others develop reactions involving multiple cell types with distinct antibodies? What mechanism directs the reaction toward platelets, RBCs, or neutrophils? How are drug-dependent antigens presented to the immune system? This latter question is particularly intriguing considering that most drugs known to induce immune cytopenias bind only weakly to target tissues.(ABSTRACT TRUNCATED AT 400 WORDS)