Abstract: FR-PO695
Dense Deposit Disease: What Makes the Deposits Dense
Session Information
- Glomerular Diseases: From Inflammation to Fibrosis - II
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: From Inflammation to Fibrosis
Authors
- Palma, Lilian MP, Universidade Estadual de Campinas, Campinas, SP, Brazil
- Madden, Benjamin J., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Sethi, Sanjeev, Mayo Clinic Minnesota, Rochester, Minnesota, United States
Background
C3 glomerulopathy (C3G) is a disease resulting from dysregulation of the alternative pathway (AP) of complement. C3G includes C3GN and DDD; both are characterized by bright glomerular C3 staining. However, on EM, DDD is characterized by dense osmiophilic mesangial and intramembranous deposits, while the deposits of C3GN are not dense.
Methods
We performed laser microdissection of glomeruli followed by mass spectrometry in 15 cases of DDD and 29 cases of C3GN to determine the proteomic profile and differences between C3GN and DDD.
Results
As expected, there was overlap in the proteomic profile of C3GN and DDD (figure 1). Both diseases showed high total spectral counts (TSC) of C3, CFHR5, CFHR1, CFHR2 and CFH. Although high TSC of terminal complement proteins (C5-C9) were present in C3GN and DDD, there was a 6-9-fold increase of C5-9 in DDD compared to C3GN. An unexpected finding was the 7-9-fold increase of apoliproteins (APO): APOE, APOA5, APOA2 and APOA4, in DDD compared to C3GN (figure 2). Controls cases showed no accumulation of APO. We also detected increased accumulation of HTRA1, C4b binding protein and SAP proteins in DDD. Immunohistochemistry is being performed to confirm and localize APO in the dense deposits of DDD and compare them with deposits in C3GN.
Conclusion
There is a higher burden of terminal complement pathway proteins in DDD compared to C3GN. In addition, extensive deposition of APOE and APOA5 likely cause the deposits to appear dense in DDD.
Overlap in the proteomic profile of C3GN and DDD.
Differences in protein expresion in DDD compared to C3GN.