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Abstract: TH-PO651

Roles of Endothelial and Mesangial Cells in the Progression of Transplant Glomerulopathy

Session Information

  • Transplantation: Basic
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • 2001 Transplantation: Basic

Authors

  • Puapatanakul, Pongpratch, Washington University in St Louis School of Medicine, St Louis, Missouri, United States
  • Husami, Samir, Washington University in St Louis School of Medicine, St Louis, Missouri, United States
  • Miner, Jeffrey H., Washington University in St Louis School of Medicine, St Louis, Missouri, United States
  • Jain, Sanjay, Washington University in St Louis School of Medicine, St Louis, Missouri, United States
  • Alhamad, Tarek, Washington University in St Louis School of Medicine, St Louis, Missouri, United States
  • Suleiman, Hani, Washington University in St Louis School of Medicine, St Louis, Missouri, United States
Background

Transplant glomerulopathy (TG) is a morphologic diagnosis characterized by reduplication of the glomerular basement membrane (GBM) on kidney allografts. Changes to the GBM and adjacent structures as TG develops and progresses have not been studied extensively at a molecular level.

Methods

Archived paraffin-embedded kidney biopsies from 9 TG patients (2 and 7 patients with Banff score cg1a and cg1b or higher [1b+], respectively), and 10 nephrectomy controls were imaged by Airyscan confocal microscopy. Immunofluorescence staining was performed using antibodies against collagen α1α1α2(IV), collagen α3α4α5(IV), laminin α5 (LG domain), and agrin as markers of GBM; CD34 as a marker of endothelial cells; vimentin as a marker of endothelial activation; and integrin α8 and α-smooth muscle actin (a-SMA) as markers of mesangial cells.

Results

There were significant increases in thickness and intensity of most GBM proteins, namely collagen α1α1α2(IV), laminin α5, and agrin at all stages of TG. Collagen α3α4α5(IV) was unchanged, suggesting that podocytes did not contribute much to GBM thickening. Laminin α5 appeared as two leaflets correlating with visible GBM reduplication by light microscopy in Banff cg1b+ TG. CD34 staining extending from capillary lumina into the thickened GBM, suggesting protrusions of endothelial cells, was observed more prominently in Banff cg1b+ TG. TG endothelial cells expressed vimentin consistently at all stages, whereas controls did not. We also observed integrin α8 and α-SMA in the reduplicated GBM in Banff cg1b+ TG, which could represent mesangial interposition as the GBM thickened at later stages.

Conclusion

We demonstrate that endothelial activation occurs early, followed by endothelial protrusion into the GBM and expansion of collagen α1α1α2(IV), highlighting the importance of endothelial injury in TG. The presence of mesangial markers in the thickened GBM later in the course of disease suggests a role for mesangial cells in TG progression. Whether these successive changes yield prognostic values requires future prospective studies.