Complement activation in early protocol kidney graft biopsies after living-donor transplantation.
BACKGROUND
To gain insight into complement activation in kidney grafts, we studied the deposition of components from all complement pathways in protocol biopsies from living-donor recipients that were taken 1 week (median 7 days) after transplantation.


METHODS
Graft protocol biopsies (n=37) were taken consecutively and stained for two-color immunofluorescence, with antibodies to C4d, C3, C1q, factor B, C6, terminal C5b-9 complement complex, mannose-binding lectin (MBL), and MBL-associated serine protease-1, combined with an endothelial marker. Light and electron microscopy were performed in all cases. Clinical acute rejection (AR), graft loss, and long-term kidney function were recorded. Baseline biopsies from 15 of the patients served as controls.


RESULTS
Endothelial C4d deposition was demonstrated in peritubular capillaries in 11 of 37 cases (30%), of which 9 of 11 (82%) experienced clinical AR but only 6 of 11 (55%) experienced AR as defined by histopathologic criteria. Biopsies from three patients, two with early graft loss, showed diffuse global C4d in the glomerular endothelium with codeposition of C3 in all patients and MBL-associated serine protease-1 in one patient. Focal peritubular capillary C3 deposition was found in two additional C4d-positive cases with AR. No posttransplant deposition was demonstrated for the other components.


CONCLUSIONS
Early diffuse C4d deposition in the kidney graft capillaries is closely related to acute humoral rejection, whereas focal staining may occur with mild AR or, rarely, without rejection. Codeposition of C3 indicates early AR with a higher risk of graft loss. In most cases, activation was limited to C4d, indicating efficient in situ regulation of complement activation.
Sund
Ståle
S
Department/Institute of Pathology, Rikshospitalet University Hospital, Oslo, Norway. stale.sund@helse-forde.no.
Hovig
Torstein
T
Reisaeter
Anna Varberg
AV
Scott
Helge
H
Bentdal
Øystein
Ø
Mollnes
Tom Eirik
TE
D000208:Acute Disease; D000328:Adult; D000368:Aged; D001706:Biopsy; D002196:Capillaries / Q000378:metabolism / Q000648:ultrastructure; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D015935:Complement C4b; D004730:Endothelium, Vascular / Q000378:metabolism / Q000648:ultrastructure; D006084:Graft Rejection / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000473:pathology*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000648:ultrastructure; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000098:blood supply; D019520:Living Donors; D037601:Mannose-Binding Lectin / Q000378:metabolism; D008854:Microscopy, Electron; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D011184:Postoperative Period; D012697:Serine Endopeptidases / Q000378:metabolism
D003176:Complement C3; D003181:Complement C4; D037601:Mannose-Binding Lectin; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d; D012697:Serine Endopeptidases