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High doses of intravenous Ig inhibit in vitro uptake of C4 fragments onto
sensitized erythrocytes
M Basta, LF Fries and MM Frank
Laboratory of Clinical Investigations, National Institutes of Allergy and
Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
We have recently reported that intravenous Ig (IVIg) inhibits uptake of
activated C3 fragments onto antibody-sensitized red blood cells (RBCs). To
elucidate the mechanism by which IVIg exerts its effect on the complement
system, we examined the possible interference with the C4 step of the
classical complement cascade. We examined the capacity of autologous serum
containing high concentrations of human IVIg to deposit C4 fragments onto
model targets (guinea pig and/or human erythrocytes sensitized with rabbit
anti-guinea pig/human erythrocytes IgG antibody). C4 binding was quantified
with radiolabeled anti-C4. Guinea pig serum with added IVIg suppressed C4
uptake onto IgG- sensitized guinea pig erythrocytes at all time points (0,
5, 15, and 30 minutes). Using sera of guinea pigs treated with increasing
doses of IVIg, this effect was shown to be dose-responsive. Serum from a
patient treated with IVIg showed reduced C4 uptake onto sensitized
homologous RBCs. In comparison with the serum from the same patient before
IVIg therapy was administered, levels were decreased almost to background.
C4 functional titers in those two samples were not different. C3 uptake was
studied in parallel with C4 to compare the degree of inhibition using sera
with increasing doses of IVIg in both the human and guinea pig system. C3
and C4 inhibition curves completely overlapped. Our findings suggest that
IVIg is an effective inhibitor of deposition of early complement activation
products (C4b, C3b) onto target surfaces and may indicate interference of
IVIg with multiple sites of complement activation.
Volume 77,
Issue 2,
pp. 376-380,
01/15/1991
Copyright © 1991 by The American Society of Hematology

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