IVIG: progress toward a better product

Intravenous immunoglobulin (IVIG) was developed for support of patients with hypogammaglobulinemia. Like so many medical landmarks, the discovery that IVIG was effective treatment for immune thrombocytopenic purpura (ITP) came from the unexpected observation that a boy with severe chronic ITP and secondary hypogammaglobulinemia had a striking increase in his platelet count following IVIG administration. IVIG subsequently became a standard treatment not only for patients with ITP but also for other autoimmune and inflammatory diseases. But IVIG production requires thousands of plasma donors, is expensive, and is sometimes in short supply. Polyclonal anti-Rh_o(D) immunoglobulin was developed as an effective treatment for ITP because the mechanism of IVIG action was thought to be hemolysis and reticuloendothelial blockade caused by anti-red cell alloantibodies. Anti-Rh_o(D) has advantages of simpler administration and fewer systemic side effects than IVIG, but its production requires immunization of Rh_o(D)-negative donors with Rh_o(D)-positive red cells. The development of an effective monoclonal immunoglobulin reagent would be a logical next step to achieve greater purity and simpler production.

In this issue, Song and colleagues (page 3708) demonstrate with mouse models that some, but not all, monoclonal antibodies with specificity for circulating cellular target antigens prevented and also reversed immune-mediated thrombocytopenia at doses down to 4-log–fold lower than standard IVIG. The effectiveness of the monoclonal antibodies correlated with their ability to block reticuloendothelial clearance of sensitized red cells. Confirmation of these observations can provide the basis for clinical trials in patients with ITP, with the goal of providing an abundant supply of an agent that does not have the potential hazards of plasma-derived products. A monoclonal antibody product may not replace IVIG for all of its many indications, but it could be an important new agent for treatment of patients with ITP who have severe and symptomatic thrombocytopenia.