Antibody responses in secondary aborting women: effect of inhibitors in blood

The perpetually high antipaternal and cell panel antibody reactivity in the blood of secondary aborting patients sets them apart from most multigravid or multiparous women. Our studies with secondary aborters' sera have shown their complement-dependent cytotoxicity (CDC) reactivity to be abolished by heat treatment (56 degrees C for 30 min) or by solid phase heparin absorptions. This is only observed if treated serum is present; a wash step restores optimal CDC activity. Thus, something in their treated serum not associated with antibody-binding to target cells is inhibiting CDC activity. A similar inhibitor was found in all human sera tested. Anticomplementary effects were excluded by showing that CDC with horse antihuman leukocyte antibody was not affected by these inhibitors. To investigate this inhibition, we designed a hemagglutination assay (HA) employing rabbit IgG-coated sheep erythrocytes and human rheumatoid factor. The results of these studies show the presence of an inhibitor (I) to both CDC and HA in normal plasma and serum. Of special interest was the presence of a heat-labile inhibitor of the inhibitor (I/I) in plasma, but not in serum. Biochemical characterization of the I is in progress. The I/I in plasma appears to be factor V of the clotting system. These observations represent a link between the immune system and clotting mechanisms, which may be important in understanding the pathophysiology of secondary abortion.