Acute antibody-mediated rejection in pancreas and kidney transplantation

Abstract

In this thesis, acute rejection after kidney, simultaneous pancreas and kidney (SPKT), and islets of Langerhans transplantation was addressed. The focus is on acute antibody-mediated rejection (AMR) after transplantation and on a potential strategy using cellular immune modulation to prevent acute rejection. First, we retrospectively evaluated the relevance of diffuse C4d-positive peritubular capillary staining in a well-defined kidney transplantation cohort with proven early acute rejections (Chapter 2). Second, the negative impact of AMR on pancreas graft survival was investigated, which proved to be significant (Chapter 3). We subsequently analyzed all SPKT patients at the LUMC with early pancreas graft loss to examine the role of AMR due to presumed thrombosis and/or acute rejection (Chapter 4). In Chapter 5, a clinical update is presented on islets of Langerhans transplantation, focusing on the alternative _-cell replacement therapy that is currently employed in the LUMC (Chapter 5). Furthermore, we reviewed the role of both lymphatic- and blood-vessel vascularization and the role of neuronal reconnection after islet transplantation with data from our own rat islet transplantation models (Chapter 6). Finally, in a rodent allogeneic islet transplantation model, we attempted to induce tolerance by using donor-derived, dexamethasone-pretreated dendritic cells (Chapter 7).