Background: MPO-ANCA (myeloperoxidase anti-neutrophil cytoplasmic antibody) is closely related to the pathogenesis of MPO-ANCA-associated glomerulonephritis through MPO-positive cells and MPO-positive cell activation. Activated MPO-positive cells, including neutrophils and monocytes, cause glomerular capillary injury via enzyme release, such as MPO. We evaluated glomerular MPO-positive cell infiltration, extracellular MPO localization and glomerular endothelial cell injury in MPO-ANCA-associated glomerulonephritis.
Methods: Renal specimens including 282 glomeruli obtained from 19 patients with MPO-ANCA-associated glomerulonephritis were analyzed. Enzyme-labeled antibody assay and immunofluorescence staining of MPO and CD34 were employed. MPO-staining was used to detect MPO-positive cells and extracellular MPO and CD34-staining was used to define glomerular endothelial cell injury. The number of MPO-positive cell infiltrations, and localization of MPO and CD34-staining areas were scored in each glomerulus. These scores were compared with the glomerular damage grading used by PAS and PAM staining.
Results: 1) MPO-positive cells increased in number in correlation with the grade of acute glomerular injury. 2) Extracellular MPO were present close to the MPO-positive cells, along the glomerular capillary walls. 3) The CD34-staining area on the glomerular capillary wall decreased, in parallel with the acute glomerular injury grading. 4) MPO depositions along the glomerular capillary wall were shown to be associated with decreased staining of CD34, with immunofluorescence staining on the same glomerular section. 5) Several glomeruli with minor abnormalities showed focal MPO-positive cell infiltration associated with the presence of MPO along the glomerular capillary wall.
Conclusion: These results suggest that MPO-positive cells and extracellular MPO play important roles in the pathogenesis of glomerular capillary injury from the early stage of MPO-ANCA-associated glomerulonephritis.