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Blood, 15 November 2001, Vol. 98, No. 10, pp. 3136-3142
TRANSFUSION MEDICINE
Accelerated autoantibody clearance by intravenous immunoglobulin
therapy: studies in experimental models to determine the magnitude and
time course of the effect
Wim K. Bleeker,
Jessica L. Teeling, and
C. Erik Hack
From the Department of Immunopathology, Central
Laboratory of the Blood Transfusion Service, Amsterdam, The
Netherlands.
Recently, it has been postulated that the beneficial effect of
intravenous immunoglobulins (IVIGs) in antibody-mediated autoimmune disorders is based on accelerated catabolism of autoantibodies. In the
current study, in vivo experiments were performed with mice in which
autoantibody production was mimicked by continuous infusion of
monoclonal antibodies. In this model, a single dose of IVIG reduced the
plasma concentrations of the infused immunoglobulin (Ig)G1 monoclonal
antibody (mAb) by approximately 40% after 3 days, whereas the
concentration of an IgA mAb was not affected. To extrapolate these
findings to humans, a computational model for IgG clearance was
established that accurately predicted the time course and magnitude of
the decrease in IgG plasma levels observed in mice. Adapted for humans,
this model predicted a gradually occurring decrease in autoantibody
levels after IVIG administration (2 g/kg), with a maximum reduction of
approximately 25% after 3 to 4 weeks and a continued decrease
of several months. In conclusion, a single high dose of IVIG induces a
relatively small but long-lasting reduction of autoantibody levels by
accelerated IgG clearance. This mechanism has clinical relevance in the
sense that it can fully explain, as the sole mechanism, the gradual
decrease in autoantibody levels observed in several patient studies.
However, in some clinical studies, larger or more rapid effects have
been observed that cannot be explained by accelerated clearance. Hence, IVIG can also reduce autoantibody levels through mechanisms such as
down-regulation of antibody production or neutralization by anti-idiotypic antibodies.
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