Circulating factor IX antigen-inhibitor complexes in hemophilia B- following infusion of a factor IX concentrate.

A persistent low-titer factor IX Inhibitor was discovered in a patIent with severe hemophllia B. The Inhibitor was very likely an immunoglobulin, since it was present in serum, was not dialyzable, retained its potency after heating to 56#{176}C, and was bound by staphylococcal protein A (SPA). When the hemophilia B patient with the inhibItor was given therapeutic infusions of factor Ix concentrate, the survival of factor IX antigen (IXA.) was markedly prolonged (ti!2 approximately 60 hr) compared to the survival of IXA. in infused hemophilia B patients lacking an inhibitor (t’!2 5 hr). The prolonged survival of IX 9 suggested the possibility of circulating immune complexes composed of 1XA. and factor IX Inhibitor (lX,,. ,). Since immunoglobulins bind to SPA via the Fc portIon of the molecule, the Fab region is free to bind to antigen. If immune complexes were formed in vivo after a factor lx concentrate infusion, IX,,5 would be retained by SPA-sepharose due to the linking of IXAC with the inhibitor molecule. As expected, postinfuslon plasma from the inhibitor patient (but not from other hemophilia B patients) showed binding of IXA#{216} to the SPA-sepharose. Further evidence for circulating complexes was provided by crossed immunoelectrophoresis using an antibody to purified factor IX. Preparations containing factor IX alone showed a single fast-moving peak in the gel, whereas postinfusion plasma from the inhibitor patient as well as mixtures In vitro of IXAC and IX, showed an additional slow-moving peak. These studies document the presence of circulating factor IX antigen-inhibitor complexes in a patient with hemophilia B and a persistent low-titer factor IX inhibitor. To date, clinical evidence of immune complex disease has not been observed.