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Abstract: SA-PO630

C3 Glomerulonephritis Has a Higher Burden of Complement Proteins Compared to Post-Infectious Glomerulonephritis

Session Information

Category: Glomerular Diseases

  • 1302 Glomerular Diseases: Immunology and Inflammation

Authors

  • Palma, Lilian MP, Universidade Estadual de Campinas Faculdade de Ciencias Medicas, Campinas, SP, Brazil
  • Theis, Jason David, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • de Holanda, Maria izabel Neves, Hospital federal de Bonsucesso, Rio de Janeiro, Brazil
  • Fervenza, Fernando C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Sethi, Sanjeev, Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background

Complement plays an important role in Post Infectious Glomerulonephritis (PIGN) and C3 glomerulonephritis (C3GN). Both PIGN and C3GN are characterized by a proliferative GN on light microscopy and bright staining for C3 on immunofluorescence studies and are difficult to distinguish on kidney biopsy. However, the etiology, pathogenesis and treatment are different for PIGN and C3GN. Given the limitations of routine kidney biopsy, we performed laser microdissection followed by mass spectrometry (MS) analysis to determine whether glomerular complement profiles are different in PIGN and C3GN.

Methods

Complement protein profiles were analyzed in patients with PIGN (n=8) and C3GN (n=9). Glomeruli (8-10 per biopsy) were laser microdissected and dissected fragments were digested into tryptic peptides and analyzed by MS. For each case 2 samples were analyzed. A list of proteins was generated and peptide identifications were accepted if greater than 90% probability by the Peptide Prophet algorithm was established. The Total spectral counts (TSC) of complement proteins of the alternative and terminal pathways (C3, C5-C9), regulatory proteins (CFH, CFHR1-5) and classical/lectin pathways (C4A, C4B) were compared between the two groups.

Results

Mean TSC of complement proteins for PIGN vs. C3GN were as follows: C3: 35.25 vs. 129.5 (p<0.05), C5-C9: 9.6 vs. 66.4 (p<0.05), CFH: 0.62 vs. 14.2 (p<0.05), CFHR1-5: 5.25 vs. 48.6 (p=NS), C4A: 0 vs. 8.11 (p=NS) and C4B: 1.25 vs. 11.6 (p<0.05). Compared to PIGN, C3 was 3.7-fold higher in patients with C3GN, as was C5-C9 (7-fold), CFH (22-fold), CFHR1-5 (9.3-fold) and C4B (9.3-fold). Only C4A had similar TSC among the two groups.

Conclusion

Glomeruli of C3GN express significantly higher levels of C3, C5-C9, and CFH when compared to PIGN . These studies show that burden of alternative and terminal complement pathway proteins is much higher in C3GN compared to PIGN, suggesting a greater role for anti-complement therapy in C3GN.