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Abstract: SA-PO629

Proteomic Analysis of Complement Proteins in Glomerulonephritis

Session Information

Category: Glomerular Diseases

  • 1302 Glomerular Diseases: Immunology and Inflammation

Authors

  • Palma, Lilian MP, Universidade Estadual de Campinas, Campinas, SP, Brazil
  • Theis, Jason David, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • 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 the pathogenesis of glomerulonephritis (GN). Even though the underlying etiology of GN might be different, complement activation results in glomerular injury and progression of disease in most GN. Routine IF includes staining for only complement proteins C3c and C1q. Therefore, with regards to evaluation of complement pathways the kidney biopsy provides limited information.

Methods

We performed laser microdissection of glomeruli in 60 cases of GN that included infection-related GN (IRG), lupus nephritis (LN), IgA nephropathy (IgAN), fibrillary GN (FG), membranous nephropathy (MN), ANCA-GN, C3GN, dense deposit disease (DDD), proliferative GN with monoclonal Ig deposits (PGNMID), monoclonal Ig deposition disease (MIDD) and immunotactoid glomerulopathy (ITG). This was followed by mass spectrometry (MS/MS) to anlayze complement proteins and pathways involved in GN.

Results

MS/MS shows that C3 followed by C9 are the most abundant complement proteins in GN, indicating activation of classical/lectin/alternative and terminal pathways, either exclusive or with combination of pathways (Figure 1). C3G, IgAN, and ANCA-GN showed alternative pathway activation. Depending on the type of GN, classical/lectin pathway activation with either C4A and/or C4B was present. Thus, MN, FG and IRG showed C4A-dominant pathways while LN, PGNMID, MIDD and ITG show C4B-dominant pathways. Significant deposition of complement regulatory proteins FHR1 and FHR5 is present in most GN.

Conclusion

This study shows accumulation of specific complement proteins in GN. The complement proteins, complement pathways and the amount of complement protein deposition is variable in different types of GN. Selective targeting of complement pathways may be a novel option in the treatment of GN.

MS/MS total spectral counts in GN. + to ++++: - negative or baseline (0-2), + (low) spectral counts between 2-5, ++ (moderate) spectral counts between 6-15, +++ (high) spectral counts between 16-50, ++++ (very high) spectral counts over 50.