On the immunogenicity of recombinant staphylokinase in patients and in animal models.
Streptokinase and staphylokinase, the presently available thrombolytic agents of bacterial origin, are immunogenic in man; their use may cause allergic reactions and/or refractoriness to renewed administration. Infusion of 2 to 10 mg of recombinant staphylokinase (STAR) in 20 patients with acute myocardial infarction or peripheral arterial occlusion induced IgG-related neutralizing activity in plasma with a lag phase of 10 to 12 days, from a baseline of 0.2 +/- 0.06 microgram STAR neutralized per ml plasma (mean +/- SEM) to a maximum of 30 +/- 6.2 micrograms/ml after 3 to 9 weeks, which persisted at a level of 14 +/- 5.8 micrograms/ml after 18 months (n = 4). In 4 baboons with a 125I-fibrin labeled clot in an extracorporeal arteriovenous loop, i.v. administration of 63 micrograms/kg STAR over 1 h, repeated at weekly intervals, induced a progressive increase of STAR-neutralizing activity (from 0.05 +/- 0.1 microgram/ml at baseline to 4.8 +/- 1.5 micrograms/ml at week 6), which was paralleled by a reduction of in vivo clot lysis (from 60 +/- 7% to 8 +/- 3%). After temporary discontinuation of STAR-administration, neutralizing activity reverted to baseline within 7 weeks, whereafter the sensitivity of in vivo clot lysis to STAR was restored. In rabbits, i.v. administration of 250 micrograms/kg STAR over 1 h, repeated at weekly intervals, also induced a progressive increase of STAR-neutralizing activity (from 0.5 +/- 0.2 microgram/ml at baseline to 6.4 +/- 1.1 micrograms/ml at week 6), which was paralleled by a reduction of in vivo clot lysis (from 68 +/- 3% to 31 +/- 7%).(ABSTRACT TRUNCATED AT 250 WORDS)
Center for Molecular and Vascular Biology, University of Leuven, Belgium.
S M
SM
Vanderschueren
J M
JM
Stassen
D
D
Collen
D000818:Animals; D000917:Antibody Formation; D001157:Arterial Occlusive Diseases / Q000188:drug therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D008297:Male; D008666:Metalloendopeptidases / Q000276:immunology* / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000188:drug therapy; D009500:Neutralization Tests; D010215:Papio; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D013997:Time Factors
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011994:Recombinant Proteins; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus