#4451 MONOCYTE MIGRATION AND ACTIVATION IN ANCA-ASSOCIATED GLOMERULONEPHRITIS

Abstract Background and Aims Glomerular injury in Anti-Neutrophil Cytoplasmic Antibodies (ANCA)-associated glomerulonephritis (AGN) is associated with macrophage infiltration. To date, their role origin remain to be fully elucidated. Activated blood monocytes likely transmigrate differentiate into kidney macrophages depending on the local microenvironment. Even remission, some studies indicate sustained monocyte activation upregulation of adhesion markers. The aim this study was research intrinsic migration capacity AGN. Targeting might open new therapeutic avenues treatment Method Transendothelial tested AGN patients active disease (n = 2), remission 8) healthy controls 6). assess adhesive migratory capacity, freshly isolated CD14 positive were added confluent TNF-α or IL1β overnight-stimulated Human Aortic Endothelial Cell (HAEC) for 30 minutes subsequently fixed. Monocyte transmigration visualized by phase-contrast microscopy quantified using ImageJ. unravel potential mechanisms driving these differences migration, we performed bulk RNA-sequencing from 4) stable 10) disease, (HC) Results adhesion, but not significantly increased during independently stimuli used mimic pro-inflammatory phenotype endothelial cells (EC) (Figure 1). During decreased found IL1β-stimulated ECs. While CD11b mRNA expression upregulated, CD11a downregulated compared HC. Two genes involved paracellular (JAML, PECAM-1) decreased. Most treated corticosteroids at time experiments. Conclusion These results suggest a remarkable increase lower minute time-frame Our findings are surprising light theorized enhanced extravasation towards diseased kidneys. Therefore, it could speculated that after longer period time, subset adherent would ultimately migrate macrophages. In long-term immunosuppressive chronic inflammation decrease adhesion. This first ex-vivo AGN, further required validate develop therapies targeting migration.