Implications of immunohistochemical detection of C4d along peritubular capillaries in late acute renal allograft rejection.
BACKGROUND
Immunohistochemical detection of the C4d complement product along peritubular capillaries (PC) may indicate humoral rejection of renal allografts. We examined the frequency of PC C4d expression in renal-allograft biopsies with acute rejection (AR) arising more than 6 months after transplantation and the impact of this finding.


METHODS
C4d was detected by immunoperoxidase in 2-micron paraffin sections of consecutive biopsies obtained over a 3-year period. The extent was classified as diffuse (> or =50% PC C4d+), focal (<50% C4d+), and negative (C4d-). Clinical data were obtained by retrospective chart review. Fifty-five AR episodes with Banff 97 types 1A (n = 13), 1B (n = 26), 2A (n = 11), 2B (n = 3), and 3 (n = 2) met inclusion criteria.


RESULTS
PC C4d expression was diffuse in 23 (42%), focal in 9 (16%), and negative in 23 (42%) biopsies. AR episodes with focal and diffuse C4d expression had higher proportionate elevation of serum creatinine at biopsy and 4 weeks after diagnosis (P< or =0.05). Biopsies with diffuse PC C4d had interstitial hemorrhage (56.5%) and plasmacytic infiltrates (52%) more frequently than C4d- biopsies (22% and 16%), P = 0.02, but had no other distinctive histologic features. Graft loss was greater in diffuse (65%) compared with focal C4d+ (33%) and C4d- (33%) groups 1 year after diagnosis, P = 0.03. Other clinical and pathologic parameters did not differ significantly, including treatment received for AR.


CONCLUSIONS
Evidence of acute cellular with occult humoral rejection is identified in more than 40% of late AR episodes. Late acute humoral rejection may be associated with interstitial hemorrhage and plasma cells and contributes significantly to graft loss.
Poduval
Rajiv D
RD
Department of Medicine, Division of Nephrology, University of Chicago, Chicago, IL 60637, USA.
Kadambi
Pradeep V
PV
Josephson
Michelle A
MA
Cohn
Richard A
RA
Harland
Robert C
RC
Javaid
Basit
B
Huo
Dezheng
D
Manaligod
Jose R
JR
Thistlethwaite
J Richard
JR
Meehan
Shane M
SM
D001706:Biopsy; D002196:Capillaries / Q000276:immunology*; D015935:Complement C4b / Q000032:analysis*; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D010446:Peptide Fragments / Q000032:analysis*; D014184:Transplantation, Homologous / Q000276:immunology* / Q000473:pathology
D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d