CX3CL1-induced CD16 monocytes extravasation in myeloperoxidase-ANCA-associated vasculitis correlates with renal damage.

BACKGROUND

Monocytes are involved in the pathogenesis of ANCA-associated vasculitis (AAV). Monocyte/macrophages are the dominant infiltrating cells in the glomeruli of patients with myeloperoxidase-AAV (MPO-AAV). However, how human monocyte subsets extravasate to the kidney in MPO-AAV with renal damage is unclear.

METHODS

30 MPO-AAV patients with renal damage and 22 healthy controls were enrolled in this study. Monocyte subsets and monocyte-related chemokines in the blood and kidneys of MPO-AAV patients were detected. The chemoattractant activity of the CX3CL1-CX3CR1 axis on CD16 monocytes was observed. The effect of MPO-ANCA on the migration of CD16 monocytes to human glomerular endothelial cells (HGECs) was detected by flow cytometry and transwell migration assay.

RESULTS

Compared with controls, CD16 monocytes were significantly decreased in the blood and increased in the glomeruli of MPO-AAV patients with renal damage. The level of CX3CL1, but not CCL2, was significantly increased in the plasma of MPO-AAV patients. CX3CL1 co-localized with glomerular endothelial cells in MPO-AAV patients with renal damage. Moreover, we initially found that MPO-ANCA promotes an increase of the chemokine CX3CL1 on HGECs, imposing recruitment on CD16 monocytes. Finally, the percentage of CD16 monocytes in the blood was found to be positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with urinary protein creatinine ratio in MPO-AAV patients with renal damage. Furthermore, the urinary protein creatinine ratio was positively correlated with the infiltrating of CD14 and CD16 cells in the kidneys.

CONCLUSION

Enhanced extravasation of CD16 monocytes to the kidney the CX3CL1-CX3CR1 axis may be involved in renal damage in MPO-AAV.