NON NEUTRALIZING ANTIBODIES TO TISSUE-TYPE PLASMINOGEN-ACTIVATOR IN THE SERUM OF ACUTE MYOCARDIAL-INFARCTION PATIENTS TREATED WITH THE RECOMBINANT PROTEIN

Recombinant tissue-type plasminogen activator (rt-PA) is currently use d as a thrombolytic agent in the management of acute myocardial infarc tion (AMI). Since it is known that other recombinant proteins induce a ntibody formation when administered to humans, we determined the prese nce of anti-rt-PA antibodies in serial blood samples from 60 AMI patie nts (43 treated with and 17 without rt-PA). Blood samples were taken u pon hospital admission, 15 days and 1, 3, 6 months thereafter. A blood sample was also collected from 200 healthy subjects. Using an ELISA, anti-rt-PA antibodies were detected as serum immunoglobulins specifica lly binding immobilized rt-PA. AMI patients before treatment and norma l subjects exhibited negligible levels of anti-rt-PA antibodies; both groups had only one outlier value. Fifteen days after rt-PA treatment, 2 AMI patients showed an increase in antibody titer beyond the highes t normal value. This titer progressively decreased during the followin g 6 months. The antibodies from these two patients bound rt-PA both in a solid and fluid phase. They bound melanoma t-PA to a lower degree a cid did not bind urokinase type plasminogen activator at all, indicati ng specificity for t-PA. The marked temporal relationship between rt-P A infusion and antibody appearance indicated that antibody formation h ad been elicited by the infusion of rt-PA. Nevertheless, the lack of a nti-rt-PA antibody interference with rt-PA function in vitro, along wi th the favourable clinical outcome of those patients having such antib odies would indicate that the appearance of anti-rt-PA antibodies does not interfere with the physiological fibrinolytic activity.