221.Serum soluble CD206 complements urinary soluble CD163 in detecting active ANCA-associated glomerulonephritis
Creators: name: William Jiemy1, 2
name: Aendekerk3, Joop P.
name: Strating2, Inge
name: Gerjan J. Dekkema2,
name: Jan-Stephan F. Sanders4,
name: Stegeman4, Coen A.
name: Little5, Mark A.
name: Heeringa2, Peter
name: Van Paassen3, Pieter
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background: </strong>Early detection of active glomerulonephritis (GN) in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is crucial to minimize kidney 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. <strong>Methods: </strong>Biopsies from ANCA GN patients were immunohistochemically (IHC) stained for CD206. The percentage of positive cells were analysed with QuPath image analysis software. Colocalization of CD163 and CD206 was assessed by immunofluorescence (IF). For ELISA, three independent cohorts (C1-Maastricht University Medical Center, C2-University Medical Center Groningen &amp; C3-Trinity College Dublin) with available serum, urine, and kidney biopsy samples (C1 only) were included. usCD163/creatinine (ng/mmol) and ssCD206 (ng/ml) were assessed in urine and serum, respectively. The performance of usCD163 and ssCD206 to detect ANCA GN was assessed using receiver operating characteristics (ROC) curves. <strong>Results: </strong>IHC revealed elevated numbers of CD206+ macrophages in the kidneys of active ANCA GN patients. CD206+ macrophages are mainly detected in the tubulointerstitial compartments. Albeit to a lower extent, CD206+ macrophages were also found in the glomerulus. CD206+ macrophage infiltration was significantly higher in crescentic class, both in the tubulointerstitial and glomerular compartments. IF showed glomerular presence of CD163+CD206- cells, whereas CD163+CD206+ and CD163-CD206+ cells were mainly found in the tubulointerstitium. For ELISA, patients (C1/C2/C3) with active ANCA GN (n=42/17/47), active non-renal AAV (n=3/3/12) or patients in remission (n=4/8/38) were included. Healthy controls (HCs; n=6) were included for C1. 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, <em>P</em>&lt;0.001). ssCD206 was significantly higher in active ANCA GN compared to patients in remission (C2 &amp; C3) and extrarenal AAV (C3) (Kruskal-Wallis, <em>P</em>≤0.0006). usCD163 had a specificity of 93% (C1), 100% (C2) and 96% (C3), whereas sensitivity was 80% (C1), 88% (C2) and 72% (C3). ssCD206 increased the sensitivity to detect active ANCA GN in all cohorts to 83% (C1), 100% (C2) and 89% (C3). <strong>Conclusion: </strong>Histological assessment revealed distinct glomerular and tubulointerstitial populations of CD163+ and CD206+ cells in the kidneys of renal active AAV patients. ssCD206 complements usCD163 and reduces false negative rates in the detection of active ANCA GN. <strong>Disclosure: </strong>Nothing to disclose.