Abstract: FR-PO585
Proteomic Analysis of Glomeruli in Myeloperoxidase-ANCA Glomerulonephritis
Session Information
- Glomerular Diseases: Lupus and Vasculitis
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1302 Glomerular Diseases: Immunology and Inflammation
Authors
- Sethi, Amit, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Grande, Joseph P., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Specks, Ulrich, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
- Fervenza, Fernando C., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
Background
Myeloperoxidase (MPO)-ANCA- associated vasculitis often involves the kidney resulting a severe necrotizing and crescentic glomerulonephritis (GN). Kidney biopsy shows varying percentages of glomeruli involved by necrotizing and crescentic lesions. Yet, a proportion of the glomeruli appear normal and uninvolved by the necrotizing and crescentic lesions. In this study, we compared the proteomic profile of involved and uninvolved glomeruli in MPO-ANCA-GN.
Methods
We performed laser microdissection of glomeruli involved be crescents/fibrinoid necrosis (CF), and glomeruli that appeared normal (N) on light microscopy in 6 cases of MPO-ANCA-GN. Equal number of glomeruli were dissected in each group/case. This was followed by mass spectrometry (MS/MS) to analyze the proteomic profile in the 2 groups. Sclerosed glomeruli were not dissected.
Results
Proteomic profile shows higher activation of complement pathways in CF glomeruli compared to N glomeruli with higher total spectral counts (TSC) of C3 (2-fold), C5 (7-fold), C7 (10 fold), C9 (6-fold). In addition, there is 3-7 fold increase in TSC of actinin 4, laminin subunit 2, fibrinogen a, fibrillin 1, agrin, nidogen-2, heat shock protein 90 in CF glomeruli compared to N glomeruli. On the other hand, there is 3-6 fold increase in TSC of desmoplakin, protein S100, and serpin B3 and B12 in N glomeruli compared to CF glomeruli.
Conclusion
Complement activation is greater in glomeruli involved by crescents and necrosis. There are also differences in proteins expressed in glomeruli with crescents/necrosis compared to uninvolved glomeruli. Overexpression of certain proteins in normal glomeruli may protect glomeruli from developing crescents/necrosis.
Funding
- Private Foundation Support