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Significance of myeloperoxidase in rapidly progressive glomerulonephritis
Abstract:
Antineutrophil cytoplasmic autoantibodies (ANCAs) are found in the sera of patients with systemic vasculitis and crescentic glomerulonephritis. We developed monoclonal antibodies against myeloperoxidase (MPO), which is a major perinuclear-ANCA antigen, and examined the presence of MPO in renal tissue from patients with rapidly progressive glomerulonephritis (RPGN) using these monoclonal antibodies. Myeloperoxidase was found in the glomeruli in four of five cases of perinuclear ANCA-positive RPGN, and the distribution pattern was different from that of immunoglobulin G. In perinuclear ANCA-negative crescentic glomerulonephritis, MPO also was detected in two of three cases. Myeloperoxidase was not detected in the capillary walls or mesangium in other nephropathies, such as minimal change disease, membranous nephropathy, and mesangial proliferative glomerulonephritis, or in normal controls. Myeloperoxidase activity was elevated and inversely correlated with the titer of MPO-ANCAs in the sera of perinuclear ANCA-associated RPGN. These data suggest that MPO plays an important role in the glomerular injury of RPGN.
Insights
Myeloperoxidase (MPO) is present in kidney tissue of patients with rapidly progressive glomerulonephritis (RPGN), suggesting its role in glomerular injury. Elevated MPO activity inversely correlates with MPO-ANCAs in RPGN sera.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Antineutrophil cytoplasmic autoantibodies (ANCAs) are associated with systemic vasculitis and crescentic glomerulonephritis.
- Myeloperoxidase (MPO) is a key antigen targeted by perinuclear-ANCAs.
Purpose of the Study:
- To investigate the presence and distribution of MPO in renal tissue of patients with rapidly progressive glomerulonephritis (RPGN).
- To explore the role of MPO in glomerular injury in RPGN.
Main Methods:
- Development of monoclonal antibodies against MPO.
- Immunohistochemical examination of renal tissue from RPGN patients and controls.
- Measurement of MPO activity in sera.
Main Results:
- MPO was detected in glomeruli of most perinuclear ANCA-positive and some ANCA-negative RPGN cases.
- MPO distribution differed from immunoglobulin G deposition.
- MPO was absent in other nephropathies and normal kidneys.
- Elevated MPO activity correlated inversely with MPO-ANCA titers in RPGN sera.
Conclusions:
- MPO is implicated in the pathogenesis of glomerular injury in RPGN.
- MPO may serve as a diagnostic marker in ANCA-associated glomerulonephritis.