The role of plasmin on the double antibody radioimmunoassay of carcinoembryonic antigen in human blood samples.

Double antibody radioimmunoassay (RIA) of carcinoembryonic antigen (CEA) on a series of freshly drawn out concurrent plasma and serum samples of normal human blood donors showed that the serum CEA values were invariably higher than the corresponding plasma CEA values. Extraneous addition of fibrinogen brought down the serum-CEA level to a value comparable to or less than the corresponding plasma value. The effect of certain factors associated with blood clotting, particularly Ca++, fibrinogen, and the fibrinolytic enzyme plasmin, was investigated. Ca++ was shown to play no role whereas the effect of fibrinogen was shown to be indirect in that it served as a specific substrate for plasmin, thereby preventing the plasmin degradation of the primary antibody used in the RIA. The finding stresses the role of enzymes like plasmin in double antibody RIA in general and may explain some of the anomalous results obtained when testing biologic material containing plasmin-like substances.