title: C4d staining in renal allograft biopsies with early acute rejection and subsequent clinical outcome.
abstract: OBJECTIVE
  Diffuse C4d staining in peritubular capillaries (PTCs) during an acute rejection episode (ARE) is the footprint of antibody-mediated rejection. In current clinical practice, diffuse C4d+ staining during acute rejection is regarded as an inferior prognostic sign. This case-control study investigated the prognostic role of mere C4d staining for graft outcome during an ARE in a well defined cohort of similarly ARE-treated patients.
  
  
  METHODS
  All kidney transplant recipients in the authors' center from January 1, 1995 to December 31, 2005 were reviewed. From these patients, 151 had a clinical ARE. Paraffin and/or frozen material was available for 128 patients showing a histologically proven ARE within the first 6 months after transplantation. All ARE patients were treated similarly with high-dose pulse steroids and in the case of steroid unresponsiveness with anti-thymocyte globulin. Biopsies were scored according to Banff criteria. Frozen and paraffin sections were stained by immunofluorescence (IF) and immunohistochemistry (IHC) for C4d, respectively, and scored for PTC positivity.
  
  
  RESULTS
  Diffuse C4d+ staining in PTCs was found in 12.5% and 4.2% sections stained by IF or by IHC, respectively. Four patients showed diffuse positive staining with both methods but showed no different risk profile from other patients. No relation between C4d staining and clinical parameters at baseline was found. C4d staining was not associated with steroid responsiveness, graft, or patient survival.
  
  
  CONCLUSIONS
  This study shows that C4d staining is not related to clinical outcome in this cohort of histologically proven early AREs.
authors.affiliation: Department of Pathology, Leiden University Medical Centre, Albinusdreef 2, L1-Q, Postbus 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Botermans
authors.forename: Hanneke
authors.initials: H
authors.lastname: de Kort
authors.forename: Michael
authors.initials: M
authors.lastname: Eikmans
authors.forename: Klaas
authors.initials: K
authors.lastname: Koop
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Baelde
authors.forename: Marko J K
authors.initials: MJ
authors.lastname: Mallat
authors.forename: Kim
authors.initials: K
authors.lastname: Zuidwijk
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
authors.forename: Emile
authors.initials: E
authors.lastname: de Heer
authors.forename: Natascha N T
authors.initials: NN
authors.lastname: Goemaere
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
authors.forename: Jan A
authors.initials: JA
authors.lastname: Bruijn
authors.forename: Johan W
authors.initials: JW
authors.lastname: de Fijter
authors.forename: Ingeborg M
authors.initials: IM
authors.lastname: Bajema
authors.forename: Marian C
authors.initials: MC
authors.lastname: van Groningen
mesh_terms: D000208:Acute Disease; D000328:Adult; D001706:Biopsy; D002196:Capillaries / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D003181:Complement C4 / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D015995:Prevalence; D011379:Prognosis; D012307:Risk Factors; D013194:Staining and Labeling / Q000379:methods / Q000706:statistics & numerical data; D014184:Transplantation, Homologous
chemical_list: D003181:Complement C4