POLYMORPHISM OF THE STREPTOKINASE GENE - IMPLICATIONS FOR THE PATHOGENESIS OF POSTSTREPTOCOCCAL GLOMERULONEPHRITIS

Recent studies of streptokinase genes from epidemiologically and clini cally defined streptococci of groups A, C and G have provided evidence of the polymorphism of the streptokinase locus in the chromosome of p athogenic streptococci. This review considers genetic and pathogenetic data suggesting that there exists a causal relationship between nephr itis strain-associated streptokinase production and the initial stages of post-streptococcal glomerulonephritis (PSGN). Currently available sequence information allows to recognize, in the middle of the strepto kinase molecule, a major variable region, V1, of about 70 amino acid r esidues in which sequence identity drops to below 50% when the protein s from nephritogenic and non-nephritogenic strains are compared. The V 1 regions, although showing microheterogeneity within either protein c ategory, appear to be more hydrophobic and possess a higher content of ordered secondary structures in the ''nephritogenic'' molecules. As a working hypothesis, they may be considered the nephrotropic domain(s) with which streptokinases from nephritogenic strains bind to glomerul ar structures and activate plasminogen in situ, thus triggering the ca scade of proteolytic processess leading to PSGN.