Antibodies to tissue-type plasminogen activator in plasma from patients with primary antiphospholipid syndrome.

A reduction in fibrinolysis has been described in association with thrombosis in the primary antiphospholipid syndrome (PAPS). In this study, we measured anti-tissue-type plasminogen activator (t-PA) antibodies and anti-fibrin-bound t-PA antibodies as possible causes of hypofibrinolysis in 39 patients with PAPS. We also evaluated the differences in anti t-PA antibodies between patients without previous thrombosis (20 patients) and patients with previous episodes of thrombosis (19 patients: deep vein thrombosis in nine, ischaemic stroke in six, arterial leg thrombosis in one, hepatic vein thrombosis in one, thrombophlebitis in one and cerebral venous thrombosis in one). Anti-t-PA antibodies were measured by an enzyme-linked immunosorbent assay (ELISA), and anti-t-PA fibrin-bound antibodies were measured by a solid-phase fibrin immunoassay (SOFIA) in 39 patients with PAPS and in 39 controls matched for gender and age. High levels of IgG anti-t-PA were found in three out of 39 patients with PAPS, and all three patients had a history of thrombosis; four other patients, one of whom had a history of thrombotic events, had high titres of antibodies directed against fibrin-bound t-PA. In addition, patients with ischaemic stroke had significantly higher levels of IgG anti-t-PA than patients without thrombosis (P = 0.029). In conclusion, our data showed that, in patients with PAPS, the highest levels of anti-t-PA antibodies were present in subjects with previous thrombotic events. The discrepancy in the results obtained with two methods of detection of anti-t-PA antibodies, ELISA and SOFIA, indicates a different interaction of the antibodies with the t-PA molecules, which are directly bound to polystyrene plates in ELISA and bound to fibrin as a bridging molecule in SOFIA.

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 used as a thrombolytic agent in the management of acute myocardial infarction (AMI). Since it is known that other recombinant proteins induce antibody formation when administered to humans, we determined the presence of anti-rt-PA antibodies in serial blood samples from 60 AMI patients (43 treated with and 17 without rt-PA). Blood samples were taken upon 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 specifically binding immobilized rt-PA, AMI patients before treatment and normal 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 highest normal value. This titer progressively decreased during the following 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 and did not bind urokinase type plasminogen activator at all, indicating specificity for t-PA. The marked temporal relationship between rt-PA infusion and antibody appearance indicated that antibody formation had been elicited by the infusion of rt-PA. Nevertheless, the lack of anti-rt-PA antibody interference with rt-PA function in vitro, along with the favourable clinical outcome of those patients having such antibodies would indicate that the appearance of anti-rt-PA antibodies does not interfere with the physiological fibrinolytic activity.

Autoimmune C1 inhibitor deficiency: report of eight patients.

PURPOSE: In this study, we investigated the clinical and biochemical features and the responses to treatment of eight patients with auto-antibody-mediated C1 inhibitor (C1-INH) deficiency and symptoms of angioedema. PATIENTS AND METHODS: In addition to the 8 patients with acquired angioedema (AAE), we also studied 36 subjects with hereditary angioedema (HAE), 15 of them treated with C1-INH plasma concentrate, and 26 patients with different autoantibodies in their plasma (10 with systemic lupus erythematosus, 6 with lupus-like anticoagulant, and 10 with chronic liver disease). Functional C1-INH was measured with the reagent kit of Immuno (Vienna, Austria); C1-INH, C4, and C1q antigen were determined by radial immunodiffusion; and autoantibodies to C1-INH were detected by an enzyme-linked immunosorbent assay method. RESULTS: Four patients with AAE had no other diseases, one had breast cancer, one liver hydatidosis, one Waldenström's disease, and one a benign M component. Functional C1-INH levels were below 30% of normal, and C1q plasma levels were low in seven patients but normal in one. Autoantibodies to C1-INH were detectable in all eight AAE patients but in none of the others. Prophylactic treatment with attenuated androgens was successful in one of four patients, and with antifibrinolytic agents (tranexamic acid) in six of seven patients. Laryngeal attacks in five patients were treated with C1-INH plasma concentrate; two patients had marked clinical and biochemical responses. In three, the symptoms resolved only with high doses, and the biochemical parameters did not significantly increase. CONCLUSIONS: Our results suggest that patients with autoimmune AAE are clinically and biochemically heterogeneous. They have different responses to treatment that seem to be related to variable C1-INH consumption.