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Abstract: TH-PO421

Glomerular Annexin A3 and Cathepsin C Staining in COVID-19-Associated and HIV-Associated Nephropathy (HIVAN)-Associated Collapsing Glomerulopathy

Session Information

Category: Glomerular Diseases

  • 1301 Glomerular Diseases: Fibrosis and Extracellular Matrix

Authors

  • Barati, Michelle T., University of Louisville, Louisville, Kentucky, United States
  • Hata, Jessica Lynn, Norton Healthcare, Louisville, Kentucky, United States
  • Brier, Michael E., University of Louisville, Louisville, Kentucky, United States
  • McLeish, Kenneth R., University of Louisville, Louisville, Kentucky, United States
  • Klein, Jon B., University of Louisville, Louisville, Kentucky, United States
  • Merchant, Michael, University of Louisville, Louisville, Kentucky, United States
Background

Prior studies demonstrated glomerular tuft staining for annexin A3 (Anxa3), a marker of parietal epithelial cells (PECs), and cathepsin C (Ctsc), a master regulatory protease, distinguishing primary collapsing glomerulopathy (CG) from other glomerular diseases. We hypothesized these staining patterns would differentiate COVID-19 associated CG (COVID-19+/CG+) from COVID-19(+) without CG (COVID-19+/CG-).

Methods

Biopsy sections used were from patients with COVID-19 infections and a pathologist-based tissue diagnoses including CG (COVID-19+/CG+; n=4) or lacking CG diagnosis (COVID-19+/CG-; n=6) were stained for Anxa3 and Ctsc using published protocols. HIVAN-associated CG (n=4) biopsies were used as a secondary CG control. Historical controls data for non-CG biospies (PMID:32561683). Glomerular staining was tabulated as for PEC staining, phenotypic characteristics of normal and activated (enlarged nuclei, hypertrophic/enlarged cuboidal shape cells, vacuolization) PECs, and for glomerular tuft to Bowman’s capsule adhesions or cellular PEC bridges. Globally scarred glomerulii were omitted from analysis. Serial section staining was used to demonstrate Anxa3 and Ctsc co-localization. Differences in the mean (i) number of glomeruli staining OR (ii) glomerular tuft area stained for Anxa3 and Ctsc per biopsy were compared by one-tailed t-test assuming an increase in staining in CG over non-glomerular disease. A p-value <0.05 was used for statistical significance.

Results

All COVID-19+/CG+ and HIVAN patients with CG demonstrated extensive Anxa3 and Ctsc glomerular tuft staining. The frequency of glomerular tuft Anxa3 and Ctsc staining and percent glomerular area was significantly (p<0.05) increased in biopsies with COVID-19+/CG+, compared to COVID-19+/CG- (log2FC 2.8-2.9). No statistical difference in frequency or area stained for Anxa3 and Ctsc was observed between COVID-19+/CG+ and HIVAN-associated CG.

Conclusion

Anxa3 and Ctsc glomerular tuft expression is increased significantly in COVID-19 and HIVAN patients with CG, mirroring our findings in primary CG. These data support the hypotheses that (a) migration of activated PECs into the glomerular tuft is a prevalent event in both primary CG and virus-associated secondary CG, and (b) glomerular Anxa3 or Ctsc may be theragnostic biomarkers of CG.

Funding

  • NIDDK Support