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CC Chemokine Ligand 18 in ANCA-Associated Crescentic GN.
- Source :
-
Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2015 Sep; Vol. 26 (9), pp. 2105-17. Date of Electronic Publication: 2015 Mar 11. - Publication Year :
- 2015
-
Abstract
- ANCA-associated vasculitis is the most frequent cause of crescentic GN. To define new molecular and/or cellular biomarkers of this disease in the kidney, we performed microarray analyses of renal biopsy samples from patients with ANCA-associated crescentic GN. Expression profiles were correlated with clinical data in a prospective study of patients with renal ANCA disease. CC chemokine ligand 18 (CCL18), acting through CC chemokine receptor 8 (CCR8) on mononuclear cells, was identified as the most upregulated chemotactic cytokine in patients with newly diagnosed ANCA-associated crescentic GN. Macrophages and myeloid dendritic cells in the kidney were detected as CCL18-producing cells. The density of CCL18(+) cells correlated with crescent formation, interstitial inflammation, and impairment of renal function. CCL18 protein levels were higher in sera of patients with renal ANCA disease compared with those in sera of patients with other forms of crescentic GN. CCL18 serum levels were higher in patients who suffered from ANCA-associated renal relapses compared with those in patients who remained in remission. Using a murine model of crescentic GN, we explored the effects of the CCL18 murine functional analog CCL8 and its receptor CCR8 on kidney function and morphology. Compared with wild-type mice, Ccr8(-/-) mice had significantly less infiltration of pathogenic mononuclear phagocytes. Furthermore, Ccr8(-/-) mice maintained renal function better and had reduced renal tissue injury. In summary, our data indicate that CCL18 drives renal inflammation through CCR8-expressing cells and could serve as a biomarker for disease activity and renal relapse in ANCA-associated crescentic GN.<br /> (Copyright © 2015 by the American Society of Nephrology.)
- Subjects :
- Aged
Animals
Biomarkers blood
Chemokine CCL8 genetics
Chemokine CCL8 metabolism
Chemokines, CC analysis
Dendritic Cells chemistry
Female
Glomerulonephritis pathology
Glomerulonephritis physiopathology
Humans
Macrophages chemistry
Male
Mice
Middle Aged
Prospective Studies
Protein Array Analysis
Receptors, CCR8 genetics
Receptors, CCR8 metabolism
Up-Regulation
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis complications
Chemokines, CC blood
Glomerulonephritis etiology
Glomerulonephritis metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1533-3450
- Volume :
- 26
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of the American Society of Nephrology : JASN
- Publication Type :
- Academic Journal
- Accession number :
- 25762060
- Full Text :
- https://doi.org/10.1681/ASN.2014040407