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Streptococcal pyrogenic exotoxin B antibodies in a mouse model of glomerulonephritis
1Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan.
Abstract:
Streptococcal pyrogenic exotoxin B is an extracellular cysteine protease. Only nephritis-associated strains of group A streptococci secrete this protease and this may be involved in the pathogenesis of post-streptococcal glomerulonephritis. Mice were actively immunized with a recombinant protease inactive exotoxin B mutant or passively immunized with exotoxin B antibody. Characteristics of glomerulonephritis were measured using histology, immunoglobulin deposition, complement activation, cell infiltration, and proteinuria. None of the mice given bovine serum albumin or exotoxin A as controls showed any marked changes. Immunoglobulin deposition, complement activation, and leukocyte infiltration occurred only in the glomeruli of exotoxin B-hyperimmunized mice. One particular anti-exotoxin B monoclonal antibody, 10G, was cross-reactive with kidney endothelial cells and it caused kidney injury and proteinuria when infused into mice. This cross-reactivity may be involved in the pathogenesis of glomerulonephritis following group A streptococcal infection.
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.
