The effect of intravenous immunoglobulin on placental transfer of a platelet‐specific antibody: Anti‐P1^A1

Abstract

The isolated perfused lobule of human placenta was used as an in-vitro model to study the effect of intravenous immunoglobulin (IVGG) on the placental transfer of a human platelet-specific antibody (anti-P1A1). Normal human IgG was shown to transfer from the maternal to the fetal circulation of the placental model after a lag period of 2-3 h. IVGG also transferred across the placenta but only after a longer lag period (3-4 h) than normal human IgG at the same concentration, which suggests that IVGG may contain a factor that inhibits the transfer of its own component IgG. The sensitive Western immunoblotting technique was used to demonstrate progressive transfer of anti-P1A1 antibody to the fetal circulation after a 2-3 h lag period. When IVGG and anti-P1A1 antibody were added simultaneously to the maternal circulation, the transfer of platelet-specific antibody was strongly inhibited by IVGG. The inhibitory effect of IVGG on anti-P1A1 antibody transfer was consistent for three different batches of the same IVGG product (Sandoglobulin). These studies provide the first scientific data to support the use of IVGG to inhibit antiplatelet antibody transfer as part of the antenatal management of neonatal alloimmune thrombocytopenia.

Transfer of Anti‐d Antibodies Across the Isolated Perfused Human Placental Lobule and Inhibition by High‐dose Intravenous Immunoglobulin: A Possible Mechanism of Action

“…The transport of IgG and its subclasses from IVIgG using a placental perfusion model has also been reported by Morgan et al (1991) and Malek et al (1995). In contrast with our findings where IgG was detectable by 1 h, both authors noted a lag phase of 2 h before IgG appeared in the fetal circulation when using Sandoglobulin IVIgG (Sandoz, Berne, Switzerland).…”

“…Presuming a likely maximum rate of transfer for total IgG (Fig 2B), the data suggest that there is competitive inhibition at the level of the syncytiotrophoblast Fcg receptor between specific anti-D IgG and the non-specific IgG present in IVIgG. Morgan et al (1991), in assessing the transfer of the platelet-specific antibody anti-Pl A1 [anti HPA1a], suggested that the IVIgG they used may contain an inhibitory factor, causing delayed transfer. It is unlikely that there is any anti-idiotypic interaction between IVIgG and anti-D since a negligible amount of complexed specific anti-D was recovered after PEG precipitation (Table III).…”

“…Although more controversial, high-dose IVIgG has also been given to the mother antenatally in the management of the fetus at risk of neonatal alloimmune thrombocytopenia (NAITP) (Bussel et al, 1988). Inhibition of placental transfer of IgG antibody by IVIgG has been demonstrated for the platelet alloantibody, anti-Pl A1 [anti HPA-1a] (Morgan et al, 1991) and this may be one of the mechanisms of action of IVIgG in NAITP.…”

“…The reason for this difference may lie with the perfusion technique used. Unlike Morgan et al (1991) and Malek et al (1995), we perfused the placenta with maternal aspects downwards. This reduces the dead space in the intervillous volume and will facilitate a rapid attainment of a steady state.…”

Receptor-Mediated Maternofetal Transfer of ImmunoglobulinsInhibition of Transport of Anti-HIV-1 Immunoglobulin by Generic Immunoglobulins in the in vitro Perfused Placenta

“…In a similar experimental model, Duncan et al [23] found that the cotransfusion of gammaglobulin and anti-RhD IgG interfered with the movement of each other across the perfused placenta. Morgan et al [24] showed that when preceded by transfusion of gammaglobulin, the rate of the platelet antibody transport was significantly reduced. We have documented in our study the inhibition of transport of HIVIG by generic immunoglobulins.…”