Detection of nephritis strain-associated streptokinase by monoclonal antibodies

Monoclonal antibodies (MAbs) N-59 and RU-1 were produced by immunisation of mice with streptokinase secreted by Streptococcus group A, type 12, strain A374 isolated from a patient with post-streptococcal glomerulonephritis (PSGN) and were characterised by Western blot analysis. MAb N-59 recognised antigenic determinants shared by both nephritis strain-associated streptokinase (NSA-SKase) and streptokinase of Streptococcus group C (C-SKase); MAb RU-1 reacted only with NSA-SKase. All nephritis-associated group A streptococcal strains tested reacted with MAb N-59; 87.5% of these strains reacted with MAb RU-1. MAb N-59 reacted with SKase produced by group G streptococcal strains isolated from patients with PSGN, and MAb RU-1 recognised SKase in two out of three of these strains.     

A comparison between streptokinase/streptodornase and streptokinase on delayed hypersensitivity skin testing

The use of streptokinase (SK) to replace streptokinase/streptodornase (SK/SD) in delayed hypersensitivity skin testing was evaluated in 325 patients. Sixty patients responded to SK/SD (100 U of SK per 25 U of SD) and 36 to SK (375 U). Thirty-two responded to SK/SD but not to SK, and eight responded to SK but not to SK/SD. SK, at the dosage used, is not a suitable substitute for SK/SD in delayed hypersensitivity testing. SD may be the more potent recall antigen. Perhaps more importantly is that of 250 positive responders to a recall-antigen battery consisting of SK/SD, SK, Candida, Trichophyton, tetanus toxoid, purified protein derivative, and coccidioidin, 99.2% (248) would have been detected had the testing for SK and SK/SD not been done.     

Henoch-Schoenlein purpura due to streptokinase

The syndrome of Henoch-Schoenlein purpura developed in a 74-year-old woman after receiving streptokinase as thrombolytic therapy for an acute myocardial infarction. Renal biopsy revealed mesangial hypercellularity with deposits of IgA. Skin biopsy also revealed IgA deposition. Immunological studies showed evidence of sensitization to streptokinase. Elevated IgG, IgA, IgM, and IgE antistreptokinase antibodies were detected in the acute serum. Positive immediate skin reactivity to streptokinase was also present. Serum precipitins to streptokinase disappeared when IgA was removed from the serum. Positive staining with biotinylated streptokinase was seen in the skin in the same pattern of distribution as IgA. These findings strongly support the role of streptokinase and IgA in the pathogenesis of Henoch-Schoenlein purpura in this patient. A control group of streptococcalinfected patients showed no immune response to streptokinase. Another control group of streptokinase-treated patients, who had no untoward reaction, had elevated immunoglobulin classes and precipitins to streptokinase. However, the precipitating antibody was IgG and streptokinase skin tests were negative.     

Discrepant changes in plasminogen by two different assays in patients receiving streptokinase

The fluorogenic synthetic substrate and radial immunodiffusion assays of plasma plasminogen were compared before and after administration of intravenous streptokinase in differing doses to 57 patients being treated for acute myocardial infarction. There was a moderate correlation (r = 0.73, slope = 0.221, intercept = 1.005, n = 57 pairs) in the two assays of plasma plasminogen before the administration of streptokinase. After streptokinase, however, the correlation of the two assays was poor (r = 0.28, slope = 0.03, y-intercept = 0.003, n = 57 pairs). The decrease in plasma plasminogen by the fluorogenic synthetic substrate assay after streptokinase averaged 95 +/- 5%, with little variation between doses. In contrast, the percentage decrease in plasma plasminogen after streptokinase by the radial immunodiffusion assay averaged only 30 +/- 11%. The percentage change in plasma plasminogen by the two assays is significantly different (P = 0.001). The discrepancy in the percentage change in plasma plasminogen after streptokinase as measured by the fluorogenic synthetic substrate assay and the radial immunodiffusion assay can be explained by a lack of specificity for the antibody to plasminogen in the radial immunodiffusion kit. Antigen-antibody precipitin rings were observed after incubation of antibody with a mixture presumed to contain plasmin, plasmin-alpha 2 antiplasmin complexes, and plasmin-fibrin/fibrinogen degradation products. Based on these data, the fluorogenic synthetic substrate assay for plasma plasminogen is a superior means of following plasminogen depletion in response to thrombolytic therapy after streptokinase treatment for acute myocardial infarction.     

Guillain-Barré syndrome following streptokinase therapy

Summary Clinical and laboratory data from a patient with Guillain-Barré syndrome indicated a probable etiological correlation of polyradiculitis to the intravenous administration of streptokinase. Oligoclonal IgG bands in the cerebrospinal fluid and serum were shown to be specific for streptokinase. Serum titers of streptokinase were elevated 64-fold for IgG, 16-fold for IgM, and 4-fold for IgA compared to controls. Clinical symptoms of Guillain-Barré syndrome are thought to result from streptokinase antibody complex mediated damage to the local blood-nerve barrier. The pathogenic relevance of autoantibodies to albumin and proteins of the central and peripheral nervous systems, occurring early after onset of symptoms, remains to be determined.Abbreviations CNS central nervous system - CSF cerebrospinal fluid - GBS Guillain-Barré syndrome - IEF isoelectric focusing - NF-L neurofilament light - PNS peripheral nervous system - SDS sodium dodecyl sulfate     

Immunologic responses to intravenous streptokinase in dogs

Streptokinase is used worldwide as a thrombolytic agent. Allergic reactions to streptokinase have been reported, but the immunologic mechanisms have not been well characterized. To develop a canine model of streptokinase immune responses analogous to human responses, four dogs received intravenous streptokinase infusions. Significant rises in IgG, IgA and IgM antibody levels occurred after streptokinase administration in three of four dogs; a fourth dog developed significant increases in IgG and IgA antibody levels. Two dogs developed immediate-type cutaneous hypersensitivity to streptokinase. One dog developed subacute dermatitis with eosinophilic infiltrates which was possibly a manifestation of an allergic reaction to streptokinase.     

Catheter-induced superior vena cava thrombosis-lysis with streptokinase and apsac (Anisoylated plasminogen streptokinase activator complex BRL 26921)

Ten patients were given thrombolytic therapy for obstructive thrombi in the superior vena cava (SVC) following catheterisation for total parenteral nutrition (TPN—8 cases) or chemotherapy (2 cases). Seven of the TPN patients were given intravenous APSAC (Beecham, BRL 26921); the other 3 were given streptokinase (SK). Five of the caval occlusions treated with APSAC cleared after between 1 and 5 doses; one of those given SK cleared after 3 days continuous infusions during which active thrombolytic potential was maintained.Intravenous APSAC should be considered for the relief of major SVC occlusive thrombosis secondary to central venous catheters.     

The streptokinase domain responsible for plasminogen binding

The limited proteolysis of soluble recombinant streptokinase by Sepharose-immobilized human plasmin(ogen) complexed with recombinant streptokinase is described. A 17 kDa streptokinase fragment comprising residues Val143 (Glu148) to Arg289 (Lys293) has been shown to be the smallest stable plasminogen binding domain. Moreover, this region seems also to be important for plasminogen activation.