Abstract: SA-PO588
Urinary Treg and Th17 Cells Identify Active Renal Disease in Patients with ANCA-Associated Vasculitis
Session Information
- Glomerular Diseases: Immunology, Inflammation - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Sonnemann, Janis, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Klocke, Jan, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Enghard, Philipp, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Eckardt, Kai-Uwe, Charité - Universitätsmedizin Berlin, Berlin, Germany
- Schreiber, Adrian, Charité - Universitätsmedizin Berlin, Berlin, Germany
Background
ANCA-associated vasculitides (AAV) cause necrotizing crescentic glomerulonephritis which is a major contributor to morbidity and mortality in AAV. As therapy relies on immunosuppressive agents with potential adverse effects, a reliable non-invasive biomarker of disease activity is needed to determine the right balance between over- and undertreatment. Since the pathogenic role of Tcells in AAV is emerging, we hypothesized that these subsets are increased in urine in active renal AAV and represent a reliable biomarker of disease activity.
Methods
Levels of Tcells and their subsets were measured in peripheral blood and urine samples from patients with active renal AAV (n=39), active non-renal AAV (n=9), AAV in remission (n=22), and healthy controls (n=9) using flow-cytometry. Urinary metabolites and cytokines (MCP-1, sCD163, sCD25, and C5a) were quantified by multiplex-analysis.
Results
Patients with active renal vasculitis show significantly higher urinary T cell counts than active non-renal, inactive, and healthy controls. In particular CD4+ T cells, T regulatory cells, and Th17 cells are significantly elevated compared to all controls. No significant difference could be shown for CD8+ T cells between active renal and remission. The only significant difference for Th1 cells was was found between active renal vasculitis and healthy controls.
sCD163, MCP-1, and C5a all show a significantly elevated concentration compared to patients in remission only sCD163 reaches significance for active renal vs. active non-renal. Analysis of receiver operator characteristics (ROC) reveals that urinary T cells identify active renal vasculitis with at least comparable diagnostic accuracy, CD3+, CD4+, CD8+ and Treg outperform soluble markers based on area under the curve (Treg AUC 0.93, sensitivity 79%, specificity 95%; CD3 Tcells AUC 0.95; sensitivity 92%, specificity 95%; MCP-1 AUC 0.9; sensitivity 60% specificity 100%, sCD163 AUC 0.92, sensitivity 96%, specificity 85%) .
Conclusion
Urinary Tcells are significantly elevated in active renal AAV and reliably determine renal disease activity. Biomarker performance for Tregs is comparable to published results of urinary MCP-1 and sCD163 and exceeds sCD25 and C5a while Th17 outperforms only sCD25 and C5a. Hence, urinary Tregs and Th17 are new potential biomarkers in AAV.