Capillary deposition of complement C4d and C3d in pediatric renal allograft biopsies.
BACKGROUND
Peritubular capillary deposition of C4d (C4d(PTC)) is a marker of antibody-mediated alloresponse and is associated with poor graft survival in adults. C3d(PTC) has received less attention; its significance is unclear. To date no information has been gained in children.


METHODS
The prevalence of C4d(PTC) and C3d(PTC) in pediatric renal allograft biopsies (n=77, 31 cadaveric kidneys) was analyzed retrospectively. Associations with histology, donor-specific antibodies (DSAs), and outcome were investigated.


RESULTS
The overall prevalence of C4d(PTC) and C3d(PTC) was 52% and 48%, respectively. C3d(PTC) was associated with C4d(PTC) (P<0.0001). Thirty-six percent of acute rejections were cellular, 28% were humoral, and 36% were combined cellular and humoral. C3d(PTC) was found in 57% of acute rejection biopsies. C4d(PTC), but not C3d(PTC), was associated with accumulation of polymorphonuclear cells in peritubular capillaries (P=0.02). Fifty-one percent of late biopsies (>6 months posttransplantation) had features of chronic allograft nephropathy: 50% were C4d(PTC_ positive, and 50% were C3d(PTC) positive. C4d(PTC) positive chronic allograft nephropathy biopsies had more transplant glomerulopathy (P=0.020) and mesangial matrix increase (P=0.026). C3d(PTC) tended to be associated with transplant glomerulopathy (P=0.06), but not with mesangial matrix increase. C4d(PTC) was correlated with DSA (P=0.011). Excluding early nonrejection graft losses, more grafts were lost in the C4d(PTC) positive group (P=0.019). C3d(PTC) was not associated with DSA or graft outcome.


CONCLUSIONS
Our results support C4d(PTC) being a hallmark of humoral rejection in pediatric renal transplantation; its presence was associated with DSA and poorer immunologic graft outcome. In contrast, C3d(PTC), although highly associated with C4d(PTC), did not correlate with DSA or outcome.
Herman
Jean
J
Department of Pediatric Transplantation, University Hospitals Leuven, 3000 Leuven, Belgium.
Lerut
Evelyne
E
Van Damme-Lombaerts
Rita
R
Emonds
Marie-Paule
MP
Van Damme
Boudewijn
B
D000293:Adolescent; D001706:Biopsy; D002196:Capillaries / Q000378:metabolism*; D002648:Child; D002908:Chronic Disease; D015933:Complement C3d / Q000378:metabolism*; D015935:Complement C4b / Q000378:metabolism*; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000378:metabolism; D006801:Humans; D007518:Isoantibodies / Q000097:blood; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology; D007684:Kidney Tubules / Q000098:blood supply*; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism*; D011184:Postoperative Period; D012189:Retrospective Studies; D014019:Tissue Donors; D014184:Transplantation, Homologous; D019737:Transplants; D016896:Treatment Outcome
D007518:Isoantibodies; D010446:Peptide Fragments; D015933:Complement C3d; D015935:Complement C4b; C032261:complement C4d