Blood, 15 September 2002, Vol. 100, No. 6, pp. 1933-1934
The mechanism of action of high-dose IgG in idiopathic
thrombocytopenic purpura
The treatment of thrombocytopenic purpura (ITP) by high-dose
IgG or much lower doses of anti-D have become mainstays of therapy. Yet
the use of these 2 effective interventions followed empiric clinical
observations that were serendipidous rather than scientifically based.
For example, in their landmark study, Imbach and coworkers demonstrated
the effectiveness of high doses of IgG in ITP (Imbach et al, The
Lancet. 1981;1:1228-1230). One hypothesized mechanism was that the
administered IgG could remove thrombocytopenia-causing immune complexes
composed of viral particles (Imbach et al, Blut. 1983;46:117-124). The
dose dependent effect of IgG on the platelet count was dramatic and
initially reinforced this postulated mechanism of action. The
observations by Fehr and associates clarified what has become the
accepted mechanism of action of IgG in ITP (Fehr et al, N Engl J Med.
1982;306:1254-1258). These investigators found that the rise in the
platelet count paralleled the inhibition of Fc-dependent RE function.
Today, 20 years later, it is not too late to try to better understand a
successful treatment. At best, progressively strategic modifications of
an effective therapy could result. At worst, enhanced clinician comfort
could be gained by knowing what was done and why it worked.
In this issue, Hansen and Balthasar (page 2087) use a rat model of
immune thrombocytopenia to study the mechanism of action of high-dose
IgG. A few initial caveats: any in vivo experiment crossing 3 species
has profound complexities. More importantly, the pathogenic,
platelet-clearing antibody was not at steady state (more about that
later). The results are compelling. Like the human situation, the
high-dose IgG raised the platelet count in a dose-dependent fashion.
But unlike the human situation, the investigators were able to measure
the pathologic antibody and found its clearance was increased by the
administered IgG.
These observations extend our understanding of the efficacy of
high-dose IgG. But questions remain: Would the same effect occur if the
pathologic antibody was produced at steady state (human disease) rather
than a single injection? If altered pathogenic antibody clearance helps
explain the effectiveness of high-dose IgG in ITP, does this mechanism
have relevance to anti-D in ITP? Questions are answered. More questions remain.
John G. Kelton
McMaster University Hamilton, Canada
