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Autoimmune sequence of streptococcal M protein shared with the intermediate filament protein, vimentin
W Kraus1, K Ohyama, D S Snyder
1Veterans Administration Medical Center, Memphis, Tennessee.
Abstract:
The crossreactivity of antibodies against a renal autoimmune epitope of Streptococcus pyogenes M protein with glomerular mesangial cells was investigated. The antibodies directed against the amino acid sequence Ile-Arg-Leu-Arg of the nephritogenic type 1 M protein reacted in a fibrillar pattern with mesangial cells cultured from isolated glomeruli. In Western blots of urea-extracted mesangial proteins, the antibodies reacted with a 56-kD protein. Monoclonal and polyclonal antibodies identified the 56-kD mesangial protein as vimentin. Two synthetic peptides of human vimentin containing the sequence Arg-Leu-Arg reacted with the autoimmune antibodies raised against a streptococcal M protein peptide. These results provide evidence that the intermediate filament protein vimentin shares autoimmune epitopes with streptococcal M protein.
Insights
Antibodies targeting Streptococcus pyogenes M protein cross-reacted with glomerular mesangial cells, identifying vimentin as a shared autoimmune epitope. This finding links bacterial proteins to autoimmune responses in kidney disease.
Area of Science:
- Immunology
- Nephrology
- Microbiology
Background:
- Autoimmune responses to Streptococcus pyogenes M protein can affect the kidneys.
- The specific mechanisms and targets of these autoimmune reactions require further elucidation.
Purpose of the Study:
- To investigate the cross-reactivity of antibodies against a specific Streptococcus pyogenes M protein epitope with glomerular mesangial cells.
- To identify potential shared antigens between the M protein and kidney cells.
Main Methods:
- Antibodies against a nephritogenic type 1 M protein peptide (Ile-Arg-Leu-Arg) were used.
- Immunofluorescence was performed on cultured human mesangial cells.
- Western blot analysis was conducted on urea-extracted mesangial proteins.
- Monoclonal and polyclonal antibodies were used to identify the target protein.
Main Results:
- Antibodies reacted in a fibrillar pattern with mesangial cells.
- A 56-kD protein in mesangial cells was identified as vimentin.
- Synthetic vimentin peptides containing the Arg-Leu-Arg sequence reacted with the M protein antibodies.
Conclusions:
- The intermediate filament protein vimentin shares autoimmune epitopes with Streptococcus pyogenes M protein.
- This cross-reactivity may play a role in the pathogenesis of kidney diseases associated with streptococcal infections.