The potential role for nephritis-associated plasmin receptor in acute poststreptococcal glomerulonephritis

Immunoglobulin G from a patient convalescing from acute poststreptococcal g lomerulonephritis (APSGN) bound specific antigenic sites in early APSGN glo meruli, A streptococcal cytoplasmic antigen (preabsorbing antigen, PA-Ag), could selectively preabsorb fluorescein isothiocyanate (FITC)-labeled IgG a nd prevented glomerular staining. The antigen was purified and identified a s an M-r similar to 43,000 protein with a pl of 4.7 that strongly activated complement C3 (N. Yoshizawa, S. Oshima, I. Sagel, J. Shimizu, and G. Trese r, 1992, J. Immunol. 148, 3110-3116). In the present study, a nephritogenic antigen was purified by affinity chromatography using APSGN IgG-immobilize d Sepharose followed by chromatography on an anion-exchange resin. Purifica tion was monitored by ELISA and Western blotting using the binding characte ristics of the specific antibodies present in APSGN serum. The molecular we ight of the purified antigen, named nephritis-associated plasmin receptor ( NAPlr), was an M-r similar to 43,000 protein and the internal amino acid se quence was found to be homologous to those of the plasmin receptor (Plr) of group A streptococci strain 64/14 and glyceraldehyde-3-phosphate dehydroge nase (GAPDH) from Bacillus subtllis. The purified NAPlr exhibited GAPDH act ivity and plasmin(ogen) binding activity. Using FITC-labeled rabbit anti-NA Plr, the antigen was found to be present in the glomeruli of 22 of 22 patie nts in the early stage of APSGN. Bacterial Plr was also demonstrated in hum an APSGN glomeruli for the first time using monoclonal antibody to the reco mbinant Plr protein. Antibody to NAPlr was found in the sera of 46 of 50 (9 2%) patients within 3 months of onset. These results led us to speculate th at NAPlr bound to the glomeruli may contribute to the pathogenesis of APSGN via plasmin and complement activation. (C) 2000 Academic Press.