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Abstract: PO1463

Differential Expression of Complement and Non-Complement Proteins in C3 Glomerulonephritis and Dense Deposit Disease

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Sethi, Sanjeev, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Madden, Benjamin J., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Fervenza, Fernando C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Palma, Lilian MP, Universidade Estadual de Campinas, Campinas, SP, Brazil
Background

C3 glomerulopathy comprising dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) results from overactivation of the alternative pathway of complement. Mass spectrometry (MS) studies have previously shown accumulation of complement proteins in C3GN and DDD. However, complete MS analysis of non-complement proteins and comparison of complement proteins in C3GN and DDD has not been done.

Methods

We performed laser microdissection of glomeruli followed by MS in 12 cases each of biopsy-proven C3GN and DDD, and 6 control cases of time 0 transplant biopsies.

Results

Compared to the controls, C3GN showed increased intensity based absolute quantification (iBAQ) values of C3 (20-fold), C5 (52-fold), C6 (76-fold), C7 (90-fold), C8 (66-fold), C9 (30-fold), CFHR1 (146-fold) and CFR5 (65-fold). Similarly, DDD showed also increased iBAQ values compared to controls of C3 (26-fold), C5 (365-fold), C6 (473-fold), C7 (261-fold), C8 (353-fold), C9 (159-fold), and CFHR1 (73-fold). When DDD was compared to C3GN, there was a 2-5 fold increase in iBAQ values in C5, C6, C7, C8 and C9 (p<0.001), although there was no significant difference in C3. Among the non-complement proteins Apolipoprotein E (APOE) and A-II and V (APOA-II and V), Serine protease HTRA1, Ryanodine receptor 1 (RYR1), and Translational activator GCN1 were expressed 3-7 fold higher in DDD compared to C3GN (p<0.001). On the other hand, proteoglycan 2 and 3 (PRG2 and 3), angiotensin (AGT) and properdin (CFP) were expressed 2-5 fold higher in C3GN compared to DDD (p<0.001).

Conclusion

MS of C3GN and DDD show high iBAQ values of complement proteins. DDD shows a higher iBAQ vaules in terminal complement proteins compared to C3GN. In addition, proteins such as APOE and APOA II/V are increased in DDD compared to C3GN, while PRG2/3 and properdin are increased in C3GN compared to DDD suggesting a role for the proteins in the pathophysiology of C3GN and DDD.

Volcano plot showing differential expression of proteins in C3GN and DDD.