Monocytes and peritubular capillary C4d deposition in acute renal allograft rejection

BACKGROUND: Peritubular capillary (PTC) deposition of complement split factor C4d in renal allografts has been shown to be closely associated with circulating antidonor antibodies and a marker for relatively poor graft survival. Monocyte/macrophage (MO) infiltration of renal allografts has been shown to adversely affect graft survival. The purpose of this study was to assess whether the two phenomena are related. METHODS: Twenty-three biopsies (from 15 patients) demonstrated diffuse strong staining of PTC for C4d (C4d+ group) and acute tubular injury with or without significant cellular rejection, while 28 biopsies (with acute rejection) but negative for PTC C4d served as controls (C4d- group). RESULTS: The C4d+ group demonstrated significantly greater glomerular and interstitial MO infiltration than did the C4d- group 3.4 +/- 2.0 vs. 0.2 +/- 0.3 MO/glomerulus, P < 0.0001; 12.9 +/- 9.2 vs. 6.5 +/- 5.0 MO/high power field (hpf), P = 0.0030]. Neutrophilic (PMN) infiltration of glomeruli and PTC was also significantly greater in the C4d+ group than in the C4d- one (0.8 +/- 0.6 vs. 0.3 +/- 0.3 PMN/glomerulus, P = 0.0003; 0.9 +/- 0.8 vs. 0.4 +/- 0.3 PTC PMN/hpf, P = 0.0035). CONCLUSION: The results indicate a close association between PTC C4d deposition and MO infiltration, particularly glomerular, and confirm previous observations regarding the correlation of PTC C4d staining and PMN infiltration.