Antibody-Mediated Rejection of the Pancreas Allograft

Abstract

Antibody-mediated rejection (AMR) is an entity that is being increasingly recognized in the setting of solid organ transplantation. Clinical, pathologic, and serologic criteria are perhaps better defined and understood in kidney and heart transplants (1), but little is known for other solid organs, including lung, pancreas, liver, and small intestine transplantation. In an effort to understand the impact and significance of alloantibodies in the setting of pancreas transplantation, we systematically screen for donor-specific antibodies (DSA) and immunolabel with C4d all pancreas allograft biopsies at our institution. In a study of 136 recipients of simultaneous pancreas and kidney transplants, we initially reported two patients with histologic evidence of both kidney and pancreas acute AMR, with diffusely C4d-positive peritubular and interacinar capillary staining, respectively. Both patients had documented circulating DSA. One patient lost both kidney and pancreas allografts 1 year posttransplant, and the second patient fully recovered kidney and pancreas allografts with normal function 2 years posttransplant (2). More recently, in our study of 18 pancreas allograft recipients and 27 biopsies, we found a significant correlation between circulating DSA and C4d staining of interacinar capillaries, and no correlation of DSA with biopsy staining of larger arteries, veins, islets, or interstitium (3). In this study, half of the patients returned to insulin therapy and half of the patients retained normal allograft function after a mean follow-up period of 316.3 days. Patients with pure acute cellular rejection fully recovered allograft function after a mean follow-up period of 208.4 days. The decreased allograft survival in AMR+pancreas recipients is in agreement with the decreased survival shown in C4d+AMR patients reported by Munivenkatappa (4). We have also looked at the potential role of C3d, another proposed tissue marker of antibody activation and deposition in kidney transplant (5). In a group of 16 pancreas allografts, C3d proved to be less sensitive than C4d in identifying patients with AMR, and there was no correlation with class I or class II DSA (Poster presentation to the 2009 ATC). We agree with the viewpoints of Dr. Munivenkatappa, Dr. Papadimitriou, and Dr. Drachenberg in their letter to the editor of this edition of Transplantation. In pancreas transplantation (as in other solid organ transplant) there is perhaps a spectrum of clinical scenarios, tissue evidence of antibody activation, and serologic patterns that still need to be defined to better understand AMR as an entity in the pancreas allograft. The diagnostic criteria for AMR in the pancreas (6) will be a subject of important discussions in the next Banff meeting in Alberta, Canada, August 2009, and will undoubtedly undergo refinement in the future. Jose R. Torrealba Department of Pathology University of Wisconsin Madison, WI Jon Odorico Department of Surgery University of Wisconsin Madison, WI