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Abstract: PO1417

Serum Soluble CD206 Complements Urinary Soluble CD163 in Detecting Active ANCA-Associated Glomerulonephritis

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Aendekerk, Joop, Department of Nephrology and Clinical Immunology, Maastricht University Medical Center, Maastricht, The Netherlands, Maastricht, Netherlands
  • Jiemy, William Febry, Department of Medical Biology and Pathology, University Medical Center Groningen, Groningen, The Netherlands, Groningen, Netherlands
  • Strating, Inge M., Department of Medical Biology and Pathology, University Medical Center Groningen, Groningen, The Netherlands, Groningen, Netherlands
  • Dekkema, Gerjan J., Department of Medical Biology and Pathology, University Medical Center Groningen, Groningen, The Netherlands, Groningen, Netherlands
  • Sanders, Jan-Stephan, Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, Groningen, The Netherlands, Groningen, Netherlands
  • Stegeman, Coen A., Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, Groningen, The Netherlands, Groningen, Netherlands
  • Little, Mark Alan, Trinity Health Kidney Centre, Trinity Translational Medicine Institute, Dublin, Ireland, Dublin, Ireland
  • Heeringa, Peter, Department of Medical Biology and Pathology, University Medical Center Groningen, Groningen, The Netherlands, Groningen, Netherlands
  • van Paassen, Pieter, Department of Nephrology and Clinical Immunology, Maastricht University Medical Center, Maastricht, The Netherlands, Maastricht, Netherlands
Background

Early detection of active glomerulonephritis (GN) in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is crucial to minimize renal damage, but accurate biomarkers are currently lacking. Urinary soluble CD163 (usCD163) has been shown as a potent biomarker for active ANCA GN. However, false negative rates can be as high as 29%. Here, we investigated whether serum soluble CD206 (ssCD206; macrophage mannose receptor), complements usCD163 in the detection of active ANCA GN.

Methods

Three independent cohorts (C1-Maastricht University Medical Center, C2-University Medical Center Groningen & C3-Trinity College Dublin) with available serum, urine, and renal biopsy samples (C1 only) were included. usCD163/creatinine (ng/mmol) and ssCD206 (ng/ml) were assessed by ELISA in urine and serum, respectively. The performance of usCD163 and ssCD206 to detect ANCA GN was assessed using receiver operating characteristics (ROC) curves. Biopsies from ANCA GN patients were immunohistochemically (IHC) stained for CD163 and CD206. Colocalization of CD163 and CD206 was assessed by immunofluorescence (IF).

Results

Patients (C1/C2/C3) had active ANCA GN (n=42/17/47), active non-renal AAV (n=3/3/12) or were in remission (n=4/8/38). Healthy controls (HCs; n=6/34/0) were included. usCD163 was significantly higher in active ANCA GN compared to active non-renal AAV and remission in all cohorts, and healthy control urine in C1 (Kruskal-Wallis, P<0.001). ssCD206 was significantly higher in active ANCA GN compared to HCs in cohorts C1 & C2 (Kruskal-Wallis, P≤0.01). usCD163 had a specificity of 100% in all cohorts, whereas sensitivity was 71 (C1), 88% (C2) and 64% (C3). The addition of ssCD206 increased the sensitivity to detect active ANCA GN in all cohorts to 83% (C1), 100% (C2) and 81% (C3). IHC revealed CD163+ and CD206+ cells in the kidneys of active ANCA GN patients (n=8). IF showed glomerular presence of CD163+CD206- cells, whereas CD163+CD206+ and CD163-CD206+ cells were mainly found in the tubulointerstitium.

Conclusion

ssCD206 complements usCD163 and reduces false negative rates in the detection of active ANCA GN. Histological assessment revealed distinct glomerular and tubulointerstitial populations of CD163+ and CD206+ cells.