title: Pancreatitis-associated protein: a putative marker for pancreas graft rejection.
abstract: BACKGROUND
  Graft rejection is one of the major causes of graft loss after pancreas transplantation. Pancreatitis-associated protein (PAP) is synthesized by the pancreas due to pancreatic inflammation and has shown to be a good serum marker for injury of the pancreas. It may also be potentially useful in the early recognition of rejection and may thus improve pancreas survival.
  
  
  METHODS
  We retrospectively evaluated PAP as an early serum marker of pancreas graft rejection in a cross-sectional study in which immunohistochemical analysis of pancreas biopsies was undertaken using antibodies against PAP. PAP concentrations were also measured in sera of blood donors and in patients with renal failure, renal replacement therapy, kidney transplantation alone, and simultaneous pancreas-kidney transplantation.
  
  
  RESULTS
  All patients had elevated PAP serum levels compared with blood donors (median PAP: 22 ng/ml, range: 5-75 ng/ml; P<0.0001). Patients on renal replacement therapy had higher values than patients with renal failure (median: 420 ng/ml and 150 ng/ml, respectively). There was a strong inverse correlation between PAP levels and creatinine clearance (P<0.001). PAP values in simultaneous pancreas-kidney transplantation patients with histological rejection were significantly higher than values in those who were clinically stable (median: 925 ng/ml and 322 ng/ml, respectively; P=0.006). Rejection was significantly associated with PAP staining of acinar cell surface. There was also a significant correlation between surface positivity of staining and serum PAP levels (P=0.008). No positive PAP staining was observed in concurrently collected biopsies of renal allografts undergoing rejection.
  
  
  CONCLUSIONS
  Serum PAP levels appear to strongly correlate with creatinine clearance measurements. In patients with a pancreas-kidney transplantation, PAP may prove to be a useful biological and histological marker of pancreatic graft rejection.
authors.affiliation: Department of Nephrology, Leiden University Hospital, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: van der Pijl
authors.forename: J G
authors.initials: JG
authors.lastname: Boonstra
authors.forename: S
authors.initials: S
authors.lastname: Barthellemy
authors.forename: Y F
authors.initials: YF
authors.lastname: Smets
authors.forename: J
authors.initials: J
authors.lastname: Hermans
authors.forename: J A
authors.initials: JA
authors.lastname: Bruijn
authors.forename: J W
authors.initials: JW
authors.lastname: de Fijter
authors.forename: M R
authors.initials: MR
authors.lastname: Daha
authors.forename: J C
authors.initials: JC
authors.lastname: Dagorn
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis*; D000951:Antigens, Neoplasm; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor; D001706:Biopsy; D003404:Creatinine / Q000378:metabolism; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D037181:Lectins, C-Type; D010179:Pancreas / Q000473:pathology; D016035:Pancreas Transplantation / Q000473:pathology; D000073718:Pancreatitis-Associated Proteins; D012189:Retrospective Studies
chemical_list: D000209:Acute-Phase Proteins; D000951:Antigens, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D003404:Creatinine