Antibody-mediated rejection (AMR) after pancreas and pancreas-kidney transplantation

Abstract

Summary Antibody‐mediated rejection (AMR) requires specific diagnostic tools and treatment and is associated with lower graft survival. We prospectively screened C4d in pancreas (n = 35, in 27 patients) and kidney (n = 33, in 21 patients) for cause biopsies. Serum amylase and lipase, amylasuria, fasting blood glucose (FBG) and 2‐h capillary glucose (CG) were also analysed. We found that 27.3% of kidney biopsies and 43% of pancreatic biopsies showed C4d staining (66.7% and 53.3% diffuse in peritubular and interacinar capillaries respectively). Isolated exocrine dysfunction was the main indication for pancreas biopsy (54.3%) and was followed by both exocrine and endocrine dysfunctions (37.1%) and isolated endocrine dysfunction (8.6%). Laboratorial parameters were comparable between T‐cell mediated rejection and AMR: amylase 151.5 vs. 149 U/l (P = 0.075), lipase 1120 vs. 1288.5 U/l (P = 0.83), amylasuria variation 46.5 vs. 61% (P = 0.97), FBG 69 vs. 97 mg/dl (P = 0.20) and 2‐h CG maximum 149.5 vs. 197.5 mg/dl (P = 0.49) respectively. Amylasuria values after treatment correlated with pancreas allograft loss (P = 0.015). These data suggest that C4d staining should be routinely investigated when pancreas allograft dysfunction is present because of its high detection rate in cases of rejection.

Pancreas transplantation, antibodies and rejection

“…These results were followed by a study on 35 pancreas allograft biopsies from 27 patients, showing rejection in 20/27 patients with C4d positivity in 15/35 biopsies [10]. DSA data were scarce, with serum samples available in 11/35 biopsies.…”

“…Still 17/35 biopsies showed signs of AMR [suspicious for AMR (n ¼ 6), chronic active AMR (n ¼ 2), or combined T-cell-mediated rejection (TCMR) and AMR (n ¼ 9)]. C4d positivity alone did not correlate with pancreas allograft survival [10]. Following these results, we studied 28 pancreas allograft biopsies from 27 patients and retrospectively showed that AMR does occur after pancreas transplantation (nine of 28), requires the presence of both diffuse interacinar C4d staining and DSA for its diagnosis, and is associated with poorer graft survival [7].…”

“…However, only those few case reports had documented C4d in pancreas transplant biopsies, although preliminary results had been discussed at the 2007 Banff Conference on Allograft Pathology. Between the 2008 [13] and 2011 [18 && ] Banff publications on pancreas allograft pathology, four other relatively large studies on the relevance of donor-specific antibodies (DSA) and AMR in pancreas transplantation were published in Banff publications on pancreas allograft pathology [6,7,9,10], and an additional case was reported [17].…”

“…As of December 2010, over 35 000 pancreas transplants have been reported worldwide to the International Pancreas Transplant registry [1]. Current 10-year pancreas graft survival rates are 68% in simultaneous pancreas kidney transplantation (SPK), 46% in pancreas after kidney transplantation (PAK), and 39% in pancreas transplantation alone (PTA) [ ], studies reporting histological findings in pancreas transplantation are scarce and progress in the development of diagnostic guidelines has been slow [6][7][8][9][10]. Pancreas allograft function is clinically most often monitored by hyperglycemia, serum amylase, serum lipase, or (when bladderdrained) amylasuria [10].…”

“…Current 10-year pancreas graft survival rates are 68% in simultaneous pancreas kidney transplantation (SPK), 46% in pancreas after kidney transplantation (PAK), and 39% in pancreas transplantation alone (PTA) [ ], studies reporting histological findings in pancreas transplantation are scarce and progress in the development of diagnostic guidelines has been slow [6][7][8][9][10]. Pancreas allograft function is clinically most often monitored by hyperglycemia, serum amylase, serum lipase, or (when bladderdrained) amylasuria [10]. These clinical tools are not accurate, and a diagnosis of acute rejection can only be established with certainty by tissue evaluation enabling the distinction between nonimmune and immune injury to the graft, and T-cellmediated versus antibody-mediated injury, guiding appropriate therapy decisions [6,7,11].…”