Is the Nephritogenic Antigen in Post-Streptococcal Glomerulonephritis Pyrogenic Exotoxin B (SPE B) or GAPDH?

Kidney Int. 2005 Sep;68(3):1120-9. doi: 10.1111/j.1523-1755.2005.00504.x.

Abstract

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amino Acid Sequence
  • Antibodies, Bacterial / blood
  • Antibody Specificity
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / immunology*
  • Biopsy
  • Child
  • Child, Preschool
  • Cysteine Endopeptidases / chemistry
  • Cysteine Endopeptidases / immunology*
  • Epitopes
  • Female
  • Glomerulonephritis / immunology
  • Glomerulonephritis / microbiology*
  • Glomerulonephritis / pathology
  • Glyceraldehyde-3-Phosphate Dehydrogenases / chemistry
  • Glyceraldehyde-3-Phosphate Dehydrogenases / immunology*
  • Humans
  • Male
  • Microscopy, Immunoelectron
  • Middle Aged
  • Molecular Sequence Data
  • Receptors, Peptide / chemistry
  • Receptors, Peptide / immunology*
  • Streptococcal Infections / complications
  • Streptococcal Infections / immunology*
  • Streptococcal Infections / pathology
  • Streptococcus pyogenes / immunology*

Substances

  • Antibodies, Bacterial
  • Bacterial Proteins
  • Epitopes
  • Plr protein, Streptococcus
  • Receptors, Peptide
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • Cysteine Endopeptidases
  • streptopain