Is the nephritogenic antigen in post-streptococcal glomerulonephritis pyrogenic exotoxin B (SPE B) or GAPDH?
BACKGROUND
Acute glomerulonephritis can follow infection by group A streptococci. An immune-complex pathogenesis is accepted, but the causative antigen(s) is still controversial. In recent years, 2 streptococcal antigens, the cationic cysteine proteinase exotoxin B (SPE B) and the plasmin receptor, a glyceraldehyde phosphate dehydrogenase (Plr, GAPDH) have attracted attention because: (1) they were localized in glomeruli in patients with acute post-streptococcal glomerulonephritis (APSGN); and (2) serum antibody to these antigens was associated with nephritogenic streptococcal infections. To date, putative nephritogens were always tested independently. Here, the relevance of SPE B and GAPDH was evaluated in the same renal biopsies and serum samples of well-defined APSGN patients.


METHODS
Renal biopsies (17 patients) and serum samples (53 patients) with APSGN and appropriate controls were examined. Immunofluorescent staining of frozen sections was performed using specific antibodies to SPE B and GAPDH. Serum antibodies were investigated by both enzyme-linked immunosorbent assay (ELISA) and Western blot methodology.


RESULTS
Glomerular deposits of SPE B were demonstrated in 12/17 APSGN biopsies, and 2 cases were borderline; circulating antibodies were found in all instances (53/53 patients). Glomerular deposition of GAPDH was detected in 1/17 biopsies, and 2 cases were borderline; circulating antibodies were found in 5/47 patients. In 31 control biopsies, only weak staining for each antigen was found in 2 cases.


CONCLUSIONS
In this study, glomerular deposits of and antibody response to zymogen/SPE B are more consistently present in APSGN than deposits and antibody response to GAPDH. Zymogen/SPE B is likely to be the major antigen involved in the pathogenesis of most cases of APSGN.
Batsford
Stephen R
SR
Department of Immunology, Institute of Medical Microbiology, Freiburg, Germany. stephen.batsford@uniklinik-freiburg.de
Mezzano
Sergio
S
Mihatsch
Michael
M
Schiltz
Emile
E
Rodríguez-Iturbe
Bernardo
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000097:blood; D000918:Antibody Specificity; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000276:immunology*; D000939:Epitopes; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D008969:Molecular Sequence Data; D018000:Receptors, Peptide / Q000737:chemistry / Q000276:immunology*; D013290:Streptococcal Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D013297:Streptococcus pyogenes / Q000276:immunology*
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D000939:Epitopes; C101055:Plr protein, Streptococcus; D018000:Receptors, Peptide; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D003546:Cysteine Endopeptidases; C042477:streptopain