Response to Yoshizawa et al.
Authors: S.R. Batsford, S. Mezzano, M. Mihatsch, E. Schiltz, B. Rodriguez-Iturbe
Journal: Kidney International (2006)

The major source of surprise to us is the fact that none of the many groups who were/are working on the theme of nephritogenic antigens in acute poststreptococcal glomerulonephritis (APSGN) have published comparative studies. Our investigation was an attempt to remedy this situation. Before addressing the points raised by Yoshizawa et al., we wish to emphasize that there is now agreement on the data concerning streptococcal zymogen/proteinase (SPE B) in APSGN. Glomerular deposition of SPE B has been independently verified,1.Cu G.A. Mezzano S. Bannan J.D. Zabriskie J.B. Immunohistochemical and serological evidence for the role of streptococcal proteinase in acute post-streptococcal glomerulonephritis.Kidney Int. 1998; 54: 819-826Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholarand has been confirmed by Yoshizawa et al. in their APSGN biopsies using antibody supplied by us (personal communication). In addition, a number of independent studies have shown antibody to SPE B to be an excellent marker of group A streptococcus infection in general (see Batsford et al.2.Batsford S.R. Mezzano S. Mihatsch M. et al.Is the nephritogenic antigen in post-streptococcal glomerulonephritis pyrogenic exotoxin B (SPE B) or GAPDH?.Kidney Int. 2005; 68: 1120-1129Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar) and it is probably the best available serological marker for APSGN.3.Parra G. Rodriguez-Iturbe B. Batsford S. et al.Antibody to streptococcal zymogen in the serum of patients with acute glomerulonephritis: A multicentric study.Kidney Int. 1998; 54: 509-517Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar The second streptococcal component studied by us was glyceraldehyde-3-phosphate dehydrogenase (GAPDH), known to be identical to plasmin receptor from group A streptococcus4.Winram S.B. Lottenberg R. The plasmin-binding protein Plr of group A streptococci is identified as glyceraldehyde-3-phosphate dehydrogenase.Microbiology. 1996; 142: 2311-2320Crossref PubMed Scopus (144) Google Scholarand sharing at least 98% homology to nephritis-associated plasmin receptor, as reported by Yoshizawa et al.5.Yamakami K. Yoshizawa N. Wakabayashi K. et al.The potential role of for nephritis-associated plasmin receptor in acute post streptococcal glomerulonephritis.Methods. 2000; 21: 185-197Crossref PubMed Scopus (62) Google Scholarthemselves. We found glomerular deposition of GAPDH in 3/17 biopsies and antibody to GAPDH in 5/47 serum samples from APSGN patients. These results demonstrate that more than one antigen may be involved in the pathogenesis of APSGN. The lower frequency of positive staining for GAPDH, found by us, is not easily explained by methodology; indirect immunofluorescence is actually more sensitive than direct staining and has been successfully used to detect glomerular deposition of many different antigens, as shown in myriad previous reports. The indirect technique is more likely to produce false-positive rather than false-negative results. Minor differences in mobility of fractions in sodium dodecyl sulfate-polyacrylamide gel electrophoresis reported between laboratories is a common phenomena of a technical nature, it does not constitute proof of real differences between antigens. Yoshizawa et al. used a quantitative immunoblot method to assess serum antibody; this is not state of the art, it should be confirmed by enzyme-linked immunosorbent assay testing. If Yoshizawa et al. are convinced of the existence of isoforms of GAPDH/plasmin receptor, they should perform complete sequencing of their antigen preparation, this task is not trivial but with modern technology it no longer poses great problems.