Abstract: FR-PO839
Immunologic Changes over Time in Repeat Kidney Biopsies from the AURORA Studies of Voclosporin in Lupus Nephritis
Session Information
- Glomerular Diseases: Inflammation and Immunology
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Parikh, Samir V., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Bolognesi, Maddalena, Universita degli Studi di Milano-Bicocca, Milano, Italy
- Grbesa, Ivana, Qiagen Digital Insights, Sibenik, Croatia
- Rovin, Brad H., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Cattoretti, Giorgio, Universita degli Studi di Milano-Bicocca, Milano, Italy
- L'Imperio, Vincenzo, Universita degli Studi di Milano-Bicocca, Milano, Italy
- Arazi, Arnon, The Broad Institute, Cambridge, Massachusetts, United States
- Hodge, Lucy S., Aurinia Pharmaceuticals Inc, Edmonton, Alberta, Canada
- Yap, Ernie, Aurinia Pharmaceuticals Inc, Edmonton, Alberta, Canada
Background
The AURORA 1 and 2 studies investigated the use of voclosporin (VCS) plus standard-of-care (SOC) for the treatment of lupus nephritis (LN). All patients underwent a kidney biopsy for enrollment (Bx1), and a subset of patients elected to undergo a second biopsy (Bx2) to assess how histology of the kidney changes in response to treatment. Here we have used multiplex immunofluorescence (mIF) to investigate changes in the immunologic landscape of the kidney in response to immunosuppression using these paired biopsies.
Methods
Formalin-fixed paraffin-embedded tissue sections were stained with MILAN technology with a 10-marker panel. Sequential acquisitions for each biopsy were registered, and autofluorescence subtracted. Dedicated ImageJ-based pipelines were used to measure total biopsy areas and immunopositive markers and/or to count cells and related positivity for markers of interest.
Results
A total of 27 paired samples were available for mIF (17 and 10 from VCS- and SOC-treated patients, respectively). CD34 and Ki67 were significantly overexpressed in Bx2 compared to Bx1 (Table 1). Within each treatment group, there was a trend toward upregulation of CD34; the differences were not statistically significant (adjusted p-values of 0.07 [VCS] and 0.12 [SOC], respectively).
Conclusion
CD34 and Ki67, which have been implicated in tissue regeneration and healing in glomerulonephritides, showed significantly higher expression in repeat biopsies of patients with LN treated with immunosuppression during the AURORA trials. The lack of difference within each treatment group may indicate a lack of concordance between clinical response and immunological landscape but may also be reflective of the small sample size. The potential utility of CD34 and Ki67 as biomarkers of response requires further investigation.
Funding
- Commercial Support – Aurinia Pharmaceuticals Inc.