TRANSFER OF ANTI-D ANTIBODIES ACROSS THE ISOLATED-PERFUSED HUMAN PLACENTAL LOBULE AND INHIBITION BY HIGH-DOSE INTRAVENOUS IMMUNOGLOBULIN - A POSSIBLE MECHANISM OF ACTION
Sj. Urbaniak et al., TRANSFER OF ANTI-D ANTIBODIES ACROSS THE ISOLATED-PERFUSED HUMAN PLACENTAL LOBULE AND INHIBITION BY HIGH-DOSE INTRAVENOUS IMMUNOGLOBULIN - A POSSIBLE MECHANISM OF ACTION, British Journal of Haematology, 96(1), 1997, pp. 186-193
Using an in vitro perfusion model, therapeutic intravenous immunoglobu
lin (IVIgG) and IgG anti-D have been shown to cross the placenta from
the maternal circuit to the fetal circuit. The transfer of all IgG spe
cies was linear with respect to time, and the amount of IgG transferre
d was proportional to the concentration of IgG in the maternal circuit
([IgG]m), but reached saturation at upper limits. With total [IgG]m a
t 6 . 5 g/l, 11 . 1 g/l or 26 . 2 g/l the increase in the fetal concen
tration of total IgG was 4 . 6 mg/l/h, 8 . 9 mg/l/h and 9 . 9 mg/l/h r
espectively. The rate of transfer of specific anti-D antibody to the f
etal circuit was 0 . 026 IU/ml/h at a concentration of 38 IU/ml in the
maternal circuit ([anti-D]m). High-dose therapeutic MgG added to the
maternal circuit (total [IgG]m 29 . 2 g/l) significantly inhibited (P
< 0 . 001) anti-D transfer to 0 . 004 IU/ml/h. Addition of the same IV
IgG at a lower concentration (total [IgG]m 11 . 1 g/l) also reduced an
ti-D transfer, but only to 0 . 015 IU/l/h. The inhibitory effect of Mg
G does not appear to be mediated by anti-idiotypic or non-specific com
plexing with the anti-D, but may be the result of competition with IgG
anti-D for placental Fc gamma receptors involved in the endocytotic u
ptake of IgG. The efficacy of IVIgG in this model suggests that it may
be clinically useful in preventing HDN and other immune cytopenias, p
rovided a sufficiently high dose is given.