Why do patients develop reactions to streptokinase?

Minor reactions to streptokinase are not uncommon, although the etiology is unknown. It is widely presumed, however, that these, like the more serious immune reactions, are antibody-mediated. We measured specific anti-streptokinase IgG, subclasses IgG1, IgG2, IgG3, IgG4 and IgE by ELISAs, haemagglutination, indirect Coombs' test and immunoblotting in six patients who developed reactions to streptokinase. Evidence of complement activation by streptokinase was sought by a haemolytic complement assay and by measurement of C3, C4 and C3d. The patients who reacted to streptokinase presented with low titres of anti-streptokinase IgG (median = 5; range 0-32) and IgG1 (median = 3; range 0-14). No evidence of any other IgG subclass was found, nor of specific anti-streptokinase IgE. Anti-streptokinase IgG1 was found to fix complement; patients who reacted to streptokinase were found to have low levels of total complement 1 year post reaction. Probable aggregates and fragments of human albumin (added stabilizer) were found in the streptokinase preparation and proved to be antigenic in some patients, but were not found to be related to the development of reactions. The findings suggest that patients who develop reactions to streptokinase cannot be predicted on the basis of antibody titres at presentation. Minor reactions to streptokinase would not appear to be antibody-mediated, although complement activation may be involved.