Capillary deposition of complement split product C4d in renal allografts is associated with basement membrane injury in peritubular and glomerular capillaries: a contribution of humoral immunity to chronic allograft rejection.
Endothelial deposition of the complement split product C4d is an established marker of antibody-mediated acute renal allograft rejection. A contribution of alloantibody-dependent immune reactions to chronic rejection is under discussion. In this study, the association of immunohistochemically detected endothelial C4d deposition in peritubular capillaries (PTC) with morphologic features of chronic renal allograft injury was investigated in a large study cohort. C4d deposits in PTC were detected in 73 (34%) of 213 late allograft biopsies performed in 213 patients more than 12 mo after transplantation (median, 4.9 yr) because of chronic allograft dysfunction. Endothelial C4d deposition was found to be associated with chronic transplant glomerulopathy (CG) (P < 0.0001), with basement membrane multilayering in PTC (P = 0.01), and with an accumulation of mononuclear inflammatory cells in PTC (P < 0,001). Furthermore, C4d deposits in PTC (in biopsies with normal glomerular morphology) were associated with development of CG in follow-up biopsies. Other morphologic features of chronic allograft nephropathy (with exception of tubular atrophy) were not associated with C4d deposits in PTC. Analyses of previous and follow-up biopsies revealed that C4d deposits may occur de novo and may also disappear at any time after transplantation. In conclusion, the data suggest that complement activation in renal microvasculature, indicating humoral alloreactivity, contributes to chronic rejection characterized by chronic transplant glomerulopathy and basement membrane multilayering in PTC.
Regele
Heinz
H
Clinical Institute of Pathology, University of Vienna, Vienna, Austria. heinz.regele@akh-wien.ac.at
Böhmig
Georg A
GA
Habicht
Antje
A
Gollowitzer
Daniela
D
Schillinger
Martin
M
Rockenschaub
Susanne
S
Watschinger
Bruno
B
Kerjaschki
Dontscho
D
Exner
Markus
M
D000328:Adult; D000917:Antibody Formation; D001485:Basement Membrane / Q000098:blood supply / Q000276:immunology / Q000473:pathology; D015415:Biomarkers; D001706:Biopsy; D003181:Complement C4 / Q000032:analysis*; D015935:Complement C4b; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007674:Kidney Diseases / Q000276:immunology / Q000473:pathology / Q000601:surgery; D007678:Kidney Glomerulus / Q000098:blood supply / Q000276:immunology / Q000473:pathology*; D016030:Kidney Transplantation / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis*; D014184:Transplantation, Homologous
D015415:Biomarkers; D003181:Complement C4; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d