title: Immunohistochemical characterization of glomerular and tubulointerstitial infiltrates in renal transplant patients with chronic allograft dysfunction.
abstract: BACKGROUND
  The term chronic allograft nephropathy (CAN) was deleted in the Eighth Banff Classification and two new categories were introduced: chronic T-cell-mediated rejection (CTMR) and chronic active humoral rejection (CAHR). The aim of this study was to revise our CAN cases diagnosed in the last 4 years, analyse allograft survival rates and identify types of infiltrating cells in the different settings.
  
  
  METHODS
  Seventy-nine patients with biopsy-proven CAN were examined and classified into four groups according to the Banff 2005 criteria: CTMR, CAHR, chronic calcineurin inhibitor toxicity (CNITOX) and interstitial fibrosis and tubular atrophy not otherwise specified (NOS). CD4, CD8, CD20, CD68, CD103, Foxp3 and IL-17 protein expression and C4d deposits were investigated.
  
  
  RESULTS
  We diagnosed 20 CTMR, 13 CAHR, 28 CNITOX, and 18 NOS. Death-censored graft survival at 4 years from renal biopsy was worse in CAHR compared with the other types of chronic injury. Glomerular CD8(+) cells were increased in CTMR vs CNITOX and NOS. Interstitial CD4(+) and CD8(+) cells were increased in CTMR vs CNITOX. CD68(+) cells in glomerular and peritubular capillaries were higher in CAHR vs CNITOX, CTMR and NOS. CD103(+) cells were higher in cases with tubulitis than in those without. T regulatory and T helper 17 cells were rarely observed in the different settings.
  
  
  CONCLUSIONS
  Graft survival was worse in patients with CAHR. The presence of any grade transplant glomerulopathy and chronic allograft vasculopathy are poorer prognostic factors. Infiltrating CD8(+), CD103(+) and CD4(+) cells may help to differentiate CTMR from other types of chronic injury, thus improving diagnostic/prognostic features of biopsy in patients with chronic allograft dysfunction.
authors.affiliation: Renal, Dialysis and Transplant Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Divella
authors.forename: Michele
authors.initials: M
authors.lastname: Rossini
authors.forename: Antonia
authors.initials: A
authors.lastname: Loverre
authors.forename: Antonio
authors.initials: A
authors.lastname: Schena
authors.forename: Annamaria
authors.initials: A
authors.lastname: Maiorano
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Gesualdo
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Zaza
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Grandaliano
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Schena
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006084:Graft Rejection / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D039001:Integrin alpha Chains / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000473:pathology* / Q000502:physiology; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014184:Transplantation, Homologous
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D016827:CD8 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D039001:Integrin alpha Chains; D020381:Interleukin-17; C091367:alpha E integrins