Inhibitors of complement-mediated cytotoxicity in normal and secondary aborter sera

Sera from patients with secondary (2 degrees) spontaneous abortions contain complement-dependent cytotoxic (CDC) antibodies with specificity for paternal lymphocytes. These lymphocytotoxins are not anti-HLA (human lymphocyte antigen) as shown by their polyspecificity on HLA select cell panels and by their removal following absorption with HLA-negative trophoblast membranes. They are predominantly IgG and have been designated as trophoblast-lymphocyte cross-reactive (TLX) antibodies. Normal and homologous 2 degrees aborter sera contain a CDC inhibitor that does not bind to paternal cells and must be present when complement is added to antibody. The inhibitor does not manifest anticomplement effects and appears to be species specific. Inhibitory capacity is increased by heating (56 degrees C for 30 min) and by absorption with heparin. When chromatographed on G-200 Sephadex, inhibitor appears in the void volume, suggesting a molecular weight of more than 250,000. It can be isolated from diethylaminoethyl cellulose into an euglobulin fraction that does not contain IgG, but does contain IgM, though no studies indicate the inhibitor to be IgM. We suggest that the inhibitor is under the control of a regulator molecule, probably an inhibitor-of-inhibitor, and that in 2 degrees aborter sera the equilibrium is unbalanced between antibody, inhibitor, and regulator.