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Abstract: SA-PO619

Experimental Anti-Glomerular Basement Membrane Glomerulonephritis Induced by a Peptide from Actinomyces

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Author

  • Shi, Yue, Peking University First Hospital, Beijing, China
Background

P14 (α3127-148) was a nephritogenic epitope for anti-GBM disease, with its core motif W136I137L139W140G142F143F145..Infections has been suspected as the“second hit”for the onset of anti-GBM disease. We aimed to search for mimicking microbial peptides that may participate in anti-GBM disease.

Methods

Blast, SYFPEITHI, ABCpred were used for searching P14-mimic microbial peptides. WKY rats and HLA-DR15+ transgenic mice were immunized with peptide B7. IHC staining, ELISA and ELISpot were applied.

Results

Peptide B7 derived from actinomyces was screened from 3319 microbial peptide under the criteria of containing the critical motif of P14, related with human infection, included both T cell and B cell epitope and high recognition for sera of anti-GBM patients. All B7-immunized rats exhibited linear deposits of IgG on the GBM. The percentage of crescent formation in glomeruli was 14.6±2.7%. For HLA-DR15+ transgenic mice, all mice immunized with B7 exhibited linear IgG deposits along the GBM and focal glomerular necrosis, two of them (28.6%) developed glomerular crescent formation. B7 also had cross-reaction with α3135-145 immunized rat splenocytes on T cell level for WKY rats model.

Conclusion

We found one microbial peptide derived from actinomyces could induce crescentic anti-GBM glomerulonephritis in both WKY rats and humanized HLA-DR15 transgenic mice. These results indicate that infections may initiate anti-GBM disease through molecular mimicry.