B lymphocytes protect islet ß cells in diabetes prone NOD mice treated with imatinib.

Imatinib (Gleevec) reverses type 1 diabetes (T1D) in NOD mice and is currently in clinical trials in individuals with recent-onset disease. While research has demonstrated that imatinib protects islet ß cells from the harmful effects of ER stress, the role the immune system plays in its reversal of T1D has been less well understood, and specific cellular immune targets have not been identified. In this study, we demonstrate that B lymphocytes, an immune subset that normally drives diabetes pathology, are unexpectedly required for reversal of hyperglycemia in NOD mice treated with imatinib. In the presence of B lymphocytes, reversal was linked to an increase in serum insulin concentration, but not an increase in islet ß cell mass or proliferation. However, improved ß cell function was reflected by a partial recovery of MafA transcription factor expression, a sensitive marker of islet ß cell stress that is important to adult ß cell function. Imatinib treatment was found to increase the antioxidant capacity of B lymphocytes, improving reactive oxygen species (ROS) handling in NOD islets. This study reveals a novel mechanism through which imatinib enables B lymphocytes to orchestrate functional recovery of T1D ß cells.

Public attitudes toward contemporary issues in liver allocation.

Allocation of scarce livers for transplantation seeks to balance competing ethical principles of autonomy, utility, and justice. Given the history and ongoing dependence of transplantation on public support for funding and organs, understanding and incorporating public attitudes into allocation decisions seems appropriate. In the context of the current controversy around liver allocation, we sought to determine public preferences about issues relevant to the debate. We performed multiple surveys of attitudes around donation and evaluated these using conjoint analysis and clarifying follow-up questions. We found little public support that allocation decisions should be based solely on risk of waiting-list mortality. Strong public sentiment supported maximizing outcomes after transplantation, prioritizing US citizens or residents, keeping organs local, and considering cost in allocation decisions. We then present a methodology for incorporating these preferences into the Model for End-Stage Liver Disease (or MELD) priority score. Taken together, these findings suggest that current allocation schemes do not accurately reflect public preferences and suggest a framework to better align allocation with the values of the public.