Abstract: FR-PO828
Siglec-9 and Its Ligand in ANCA-Associated Vasculitis
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
- Kidder, Dana, NHS Grampian, Aberdeen, Aberdeen, United Kingdom
- Walls, Catriona, University of Aberdeen, Aberdeen, United Kingdom
- Yoldi, Jon, University of Aberdeen, Aberdeen, United Kingdom
- Satchell, Simon C., University of Bristol Bristol Renal, Bristol, United Kingdom
- De Bari, Cosimo, University of Aberdeen, Aberdeen, United Kingdom
Background
Sialic acid-binding Ig-like lectin 9 (Siglec-9) is expressed on leukocytes. The expression and role of siglec-9 and its ligand in the context of ANCA-associated vasculitis (AAV) is unknown.
Methods
Leukocytes and serum were isolated from venous blood and siglec-9 expression analysed by flow cytometry/ELISA. Leukocytes were stimulated with MPO/PR3 to assess Siglec-9 shedding. An Fc protein was used to identify ligands under inflammatory conditions (TNF-α/C5a) on conditionally immortalised glomerular endothelial cells (ciGEnC) or AAV renal sections. BulkRNA sequencing will hilight biological relevance of ligand interactions.
Results
Neutrophils and intermediate monocytes from MPO-AAV patients had reduced Siglec-9 expression versus PR3-AAV. Stimulation of neutrophils with MPO, not PR3, induced a shedding phenotype (Fig. 1). Analysis of serum showed decreased Siglec-9 in MPO-AAV compared to PR3-AAV. A positive correlation of serum Siglec-9 was detected with disease activity and MPO-ANCA titre. Siglec-9 ligand was identified on glomerular endothelial cells from kidney biopsies of AAV patients and two distinct patterns of expression on ciGEnC, which was altered under inflammatory conditions.
Conclusion
Cellular and serum Siglec-9 expression differs in MPO and PR3-AAV and may be influenced by ANCA serotype. Positive Siglec-9 ligand expression on ciGEnC suggests a direct interaction between Siglec-9 on leukocytes and glomerular endothelium. Our data suggest a possible role for Siglec-9/ligand interactions in the context of AAV - but further study is required to assess the biological relevance of these findings.
Funding
- Clinical Revenue Support