title: Implications of immunohistochemical detection of C4d along peritubular capillaries in late acute renal allograft rejection.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Nephrology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Rajiv D
authors.initials: RD
authors.lastname: Poduval
authors.forename: Pradeep V
authors.initials: PV
authors.lastname: Kadambi
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Josephson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Cohn
authors.forename: Robert C
authors.initials: RC
authors.lastname: Harland
authors.forename: Basit
authors.initials: B
authors.lastname: Javaid
authors.forename: Dezheng
authors.initials: D
authors.lastname: Huo
authors.forename: Jose R
authors.initials: JR
authors.lastname: Manaligod
authors.forename: J Richard
authors.initials: JR
authors.lastname: Thistlethwaite
authors.forename: Shane M
authors.initials: SM
authors.lastname: Meehan
mesh_terms: 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
chemical_list: D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d