Myeloperoxidase (MPO) Immunostaining Can Identify Endothelial Injury of Peritubular Capillaries and Glomeruli in Renal Antibody Mediated Rejection
Background: C4d positive staining in peritubular capillaries (PTC) of renal grafts has been used as a marker to support antibody mediated rejection (AMR), if there are morphologic changes of AMR and the renal recipient has positive donor specific antibody. But it is not clear if the C4d staining is related to any peritubular and glomerular injury during AMR. As injured endothelial cells can uptake the MPO into the endothelial cells, we used MPO immunostaining to highlight glomerular endothelial injury in crescentic glomerulonephritis previously. The goal of this study was to determine if there was an endothelial injury of PTC and glomeruli that can correlate with patients’ elevated serum creatinine levels (sCr). Design: The study included one group of negative native renal controls from tumor related nephrectomies (n=12), one group of transplant biopsies with borderline changes (BC) as transplant controls (n=19), and one group of renal transplant biopsies with AMR as the study group (acute/chronic, n=23). All three groups of cases were stained for MPO immunohistochemically and the MPO expressions in the endothelium of PTC and glomeruli were evaluated for staining intensity and % of involved capillaries; multiplying the intensity and the positive % generated the final combined scores (H score). These MPO indices were correlated with sCr. Results: AMR group (3.72±0.45 mg/dl) had significantly higher sCr than native controls (0.89±0.06 mg/dl) and transplant controls (2.23±0.20 mg/dl). The native control group and the transplant controls showed no MPO expression in endothelium of glomeruli and PTC. However, there were MPO positive stains in the endothelial cells of both glomeruli (16/23 cases, 69.5%) and peritubular capillaries (17/23 cases, 73.9%) in the biopsies with AMR (Figure and Table). There were significant correlations between the peritubular MPO staining versus sCr (r=0.355 and p= 0.0106), and glomerular MPO staining versus sCr (r=0.355 and p=0.0106 ) (n=54 cases from three groups). Also the H scores of glomerular MPO expression were significantly correlated with that of peritubular MPO staining (r=0.645, and p=0.0001). Conclusions: Our data indicate that MPO staining identified endothelial injuries in both glomeruli and PTC of AMR cases, which were significantly correlated with sCr. The endothelial injuries in both capillary beds may be related to C4d and other activated complement mediated damage during the AMR.