Blood, 1 May 2003, Vol. 101, No. 9, pp. 3344-3344
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-Rho(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-Rho(D) has advantages of
simpler administration and fewer systemic side effects than IVIG, but
its production requires immunization of Rho(D)-negative donors with Rho(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.
James N. George
The University of Oklahoma Health Sciences
Center
