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Detection of urinary macrophages expressing the CD16 (Fc gamma RIII) molecule: a novel marker of acute inflammatory
1Department of Nephrology, Sendai Shakaihoken Hospital, Japan. hottao@remus.dti.ne.jp
Background:
The CD16 antigen is the Fc gamma receptor III. CD14+CD16+ cells are proinflammatory monocytes/macrophages (Mo/M phi) that constitute a minor population in the peripheral blood of healthy individuals. Little is known about the expression of CD16 antigen on Mo/M phi in glomerulonephritis.
Methods:
Flow cytometric analyses were performed on urine and blood samples obtained from 209 patients with various renal diseases. Patients variously suffered from rapidly progressive crescentic glomerulonephritis (RPGN), membranoproliferative glomerulonephritis (MPGN), postinfectious acute glomerulonephritis (AGN), Henoch-Schönlein purpura nephritis (HSPN), IgA nephropathy (IgAN), membranous nephropathy (MN), minimal change nephrotic syndrome (MCNS), lupus nephritis (LN), acute interstitial nephritis, hereditary nephropathy, idiopathic renal hematuria (IRH), and renal stone.
Results:
The CD16+ M phi population of cells was present in the urine of hematuria-positive patients with proliferative glomerulonephritis, including AGN, IgAN, RPGN, MPGN, and LN with acute inflammatory lesions, such as endocapillary proliferation, tuft necrosis, and cellular crescents. In contrast, the urinary CD16+ M phi population was negligible in hematuria-positive patients with nonproliferative renal disease, including hereditary nephropathy, IRH, and renal stone and also in patients with proliferative glomerulonephritis lacking acute inflammatory lesions. Total urinary M phi of these patients were much less than those of patients having proliferative glomerulonephritis with acute inflammatory lesions. Transient expansion of the CD16+ M phi population in urine was observed during the acute exacerbation of urinary abnormalities, whereas the disappearance of CD16+ M phi closely preceded the amelioration of urinary abnormalities in patients with proliferative glomerulonephritis. In 38 of the 98 patients positive for CD16+ M phi population in urine, the CD16+ Mo population was negligible in peripheral blood. Immunohistochemically, CD16+ M phi were present in the glomeruli of active proliferative glomerulonephritis, whereas such cells were absent in inactive proliferative glomerulonephritis or nonproliferative glomerular diseases.
Conclusion:
CD16+ M phi may be effector cells involved in the acute inflammation common to all types of proliferative glomerulonephritis. Furthermore, the detection of CD16+ M phi in urine, as well as urinary M phi counts, may serve as a useful indicator of the active stage of proliferative glomerulonephritis.
Insights
CD16+ macrophages in urine indicate active proliferative glomerulonephritis. Their presence signifies inflammation, while their absence suggests improvement, making them potential biomarkers for disease activity.
Area of Science:
- Immunology
- Nephrology
- Cell Biology
Background:
- CD16 is Fc gamma receptor III.
- CD14+CD16+ cells are proinflammatory monocytes/macrophages (Mo/M phi).
- Limited knowledge exists on CD16+ Mo/M phi in glomerulonephritis.
Purpose of the Study:
- Investigate CD16 antigen expression on Mo/M phi in various renal diseases.
- Determine the role of CD16+ Mo/M phi in glomerulonephritis pathogenesis.
- Evaluate CD16+ Mo/M phi as potential biomarkers for active disease.
Main Methods:
- Flow cytometry on urine and blood samples from 209 renal disease patients.
- Analysis included various glomerulonephritis types (RPGN, MPGN, AGN, HSPN, IgAN, LN) and other renal conditions.
- Immunohistochemistry on kidney biopsies.
Main Results:
- CD16+ M phi were abundant in urine of patients with active proliferative glomerulonephritis (AGN, IgAN, RPGN, MPGN, LN).
- Urinary CD16+ M phi were negligible in nonproliferative diseases and inactive proliferative glomerulonephritis.
- Urinary CD16+ M phi levels correlated with disease activity, increasing during exacerbations and decreasing with improvement.
Conclusions:
- CD16+ M phi are likely effector cells in acute inflammatory proliferative glomerulonephritis.
- Urinary CD16+ M phi detection and counts may indicate active proliferative glomerulonephritis.
- CD16+ M phi serve as potential biomarkers for monitoring glomerulonephritis activity.