The pathogenic mechanisms leading to acute post streptococcal glomerulonephritis (APSGN) and its progression to the chronic stages are still not completely understood. With respect to ASPGN, work in this laboratory had previously implicated a protein celled nephritis strain associated protein (NSAP) by establishing its presence in all nephritis strains, its presence in APSGN biopsies using polyclonal antibodies to ECP and the appearance of antibodies to the protein in the sera of APSGN patients. Using a monoclonal antibody called RU1 thought to be directed against NSAP, we recently isolated another nephritis strain associated protein which was group A streptokinase. However, both monoclonal and polyclonal antibodies to the purified material did not stain APSGN biopsies; studies of human sera with this protein were not diagnostic and animal studies with this purified streptokinase showed only minimal glomerular damage suggesting the original NSAP was different from the streptococcal kinase. In view of the discrepancies noted above, we plan to reexamine the ECP of nephritic and non nephritic strains of streptococci for the original NSAP which we believe is distinct from GRA streptokinase. Monoclonal and polyclonal sera will be prepared against this antigen and biopsies of APSGN patients will be stained with these new antibodies. APSGN and control sera will be used to determine whether they react specifically against this new protein. Using a gT/11 gene bank from strain A374 and/or A207 we will isolate the NSAP gene in a fashion similar to that accomplished for the group A streptokinase gene. The importance of identifying the nephritogenic protein cannot be overemphasized since between 5-10% of APSGN patients go on to chronic end stage renal disease. A vaccine prepared from a antigenically modified nephritogenic protein could prevent both the acute and chronic forms of this disease.
| Cu, G A; Mezzano, S; Bannan, J D et al. (1998) Immunohistochemical and serological evidence for the role of streptococcal proteinase in acute post-streptococcal glomerulonephritis. Kidney Int 54:819-26 |
| Poon-King, R; Bannan, J; Viteri, A et al. (1993) Identification of an extracellular plasmin binding protein from nephritogenic streptococci. J Exp Med 178:759-63 |
