Challenges in the Diagnosis of Chronic Antibody Mediated Rejection Due to Loss of Peritubular Capillaries and Low Extent and Transient Nature of C4d Deposition
AB Collins, AB Farris, RN Smith, CD Adams, PA Della Pelle, S Saidman, W Wong, RB Colvin. Massachusetts General Hospital, Boston, MA
Background: The diagnosis of acute antibody mediated rejection (AMR) is based on C4d deposition in >50% of peritubular capillaries (PTC). However, a loss of peritubular capillaries has been reported in late graft biopsies. Here we test whether the same criteria of C4d extent are appropriate for chronic AMR.
Design: All available cases of chronic humoral rejection (CHR) (1997-2008) were stained with two color immunohistochemistry for CD34 and C4d and compared with transplant glomerulopathy and no C4d (TG C4d-), chronic calcineurin inhibitor toxicity (CNIT), and normal transplant biopsies (NT). PTC density was quantitated visually and by morphometry (Aperio) and correlated with graft function and fibrosis (morphometry).
Results: Biopsies with CHR or TG C4d- had significantly reduced PTC density compared with NT (Table). Within the CHR group, the density of C4d+ PTC correlated with the overall capillary density (p=0.001). There was a wide spectrum of the % of PTC with (1-90%). Most cases (9) were Banff C4d2 (10-50%); a minority (7) were C4d3 (>50%). Most CHR cases had glomerular capillary wall C4d deposition (83%). The % fibrosis correlated with the Cr at the time of biopsy (p=0.04). C4d%+ and PTC density showed no statistically significant correlation with Cr at the time of the biopsy. PTC density was decreased with time post-transplant. Our data suggest that some TG C4d- cases are the sequelae C4d+ lesions, since 2/7 had had prior acute AMR. Furthermore one of the C4d+ CHR cases had a later biopsy that was TG C4d-. All of the CHR recipients tested had donor specific antibody (5 class I only, 6 class II only and 2 both), including the one with 1% C4d+ PTC and C4d+ glomeruli. Aperio microvascular counts were highly correlated with visual counts (r=0.928), although they were consistently higher.
|Diagnosis||N||yrs post tx||CD34||C4d||%C4d+||p vs NT|
Conclusions: Diagnotic criteria of CHR should acknowledge the substantial decrease of capillary density and common occurrence of <50% C4d postive PTC. Glomerular C4d in the absence of glomerulonephritis may be a helpful criterion. C4d deposition can be transient in PTC while the TG persists.
Category: Kidney (does not include tumors)
Monday, March 9, 2009 9:15 AM
Platform Session: Section G 1, Monday Morning