The histological development of acute antibody-mediated rejection in HLA antibody-incompatible renal transplantation.
BACKGROUND
The aim of this study was to examine the development of acute antibody-mediated rejection in HLA antibody-incompatible renal transplantation in relation to the Banff 07 histological classification.


METHODS
Renal biopsies were scored using the Banff 07 diagnostic criteria, and paraffin-embedded sections were stained with the pan-leucocyte marker CD45.


RESULTS
Thirty-six patients had 72 renal biopsies. In biopsies performed 30 min after graft reperfusion, the mean number of CD45+ cells per glomerulus was higher than in control grafts (P < 0.04) and was associated with the donor-specific antibody (DSA) level at transplantation measured by microbeads (P < 0.01), and eight out of nine patients with greater than five CD45+ cells per glomerulus had early post-transplant rejection or oliguria, compared to 11 out of 20 with less than five cells per glomerulus (P < 0.01). In the first 10 days post-transplant, although peritubular capillary (PTC) leucocyte margination grade 3 and C4d deposition were specific for rejection, their sensitivities were low. PTC C4d staining was only seen in two out of 11 biopsies taken in the first 5 days after transplant, even in the presence of rejection, but was present in the majority of later biopsies with rejection. In biopsies stained for CD3, CD68 and CD20, it was notable that CD20+ cells were not seen during acute rejection, the infiltrates comprising CD3+ and CD68+ leucocytes.


CONCLUSIONS
Glomerular margination of leucocytes occurred early after transplantation and was associated with DSA level and early graft dysfunction. The Banff 07 PTC margination scoring system was easy to apply, especially when CD45 staining was used, and PTC margination grade 3 was always associated with clinical rejection.
Higgins
Rob
R
Transplant Unit, University Hospitals Coventry and Warwickshire, Coventry, West Midlands, UK. Robert.Higgins@uhcw.nhs.uk
Zehnder
Daniel
D
Chen
Klaus
K
Lowe
David
D
McKinnell
Joanna
J
Lam
For T
FT
Kashi
Habib
H
Tan
Lam Chin
LC
Imray
Chris
C
Fletcher
Simon
S
Krishnan
Nithya
N
Hamer
Rizwan
R
Briggs
David
D
D000293:Adolescent; D000328:Adult; D015935:Complement C4b / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007674:Kidney Diseases / Q000628:therapy; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D055815:Young Adult
D006680:HLA Antigens; D007074:Immunoglobulin G; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d