Streptococcal pyrogenic exotoxin B antibodies in a mouse model of glomerulonephritis

Y-H Luo1, C-F Kuo, K-J Huang

  • 1Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan.

Kidney International
|July 20, 2007
PubMed

Insights

Group A Streptococcus exotoxin B contributes to nephritis. Antibodies against this exotoxin B can cause kidney damage, suggesting a role in post-streptococcal glomerulonephritis pathogenesis.

Area of Science:

  • Microbiology
  • Immunology
  • Nephrology

Background:

  • Streptococcal pyrogenic exotoxin B (SpeB) is an extracellular cysteine protease secreted by nephritis-associated strains of group A Streptococcus.
  • SpeB may play a role in the pathogenesis of post-streptococcal glomerulonephritis (PSGN).

Purpose of the Study:

  • To investigate the role of SpeB in the development of glomerulonephritis.
  • To determine if antibodies against SpeB contribute to kidney pathology.

Main Methods:

  • Mice were actively immunized with an inactive SpeB mutant or passively immunized with anti-SpeB antibodies.
  • Kidney pathology was assessed via histology, immunoglobulin deposition, complement activation, cell infiltration, and proteinuria.
  • A specific anti-SpeB monoclonal antibody (10G) was tested for cross-reactivity with kidney cells and its effect on kidney function.

Main Results:

  • Active or passive immunization with SpeB induced glomerulonephritis characteristics, including immunoglobulin deposition, complement activation, and leukocyte infiltration in mice.
  • Control mice (bovine serum albumin or exotoxin A) showed no significant changes.
  • The anti-SpeB monoclonal antibody 10G exhibited cross-reactivity with kidney endothelial cells, leading to kidney injury and proteinuria upon infusion.

Conclusions:

  • Group A Streptococcus exotoxin B is implicated in the pathogenesis of post-streptococcal glomerulonephritis.
  • Immune responses targeting SpeB, particularly cross-reactive antibodies, can directly cause kidney damage and contribute to PSGN development.

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