Monitoring Inflammation, Humoral and Cell-mediated Immunity in Pancreas and Islet Transplants

Abstract

Type 1 diabetes (T1D) is caused by the chronic autoimmune destruction of insulin producing beta cells. Beta cell replacement therapy through whole pancreas or islet transplantation is a therapeutic option for patients in which a stable glucose control is not achievable with exogenous insulin therapy. Long-term insulin independence is, however, hampered by the recipient immune response that includes activation of inflammatory pathways and specific allo- and auto-immunity. The identification and monitoring of soluble and cellular biomarkers are of critical relevance for the prediction of graft damage, for the evaluation of responses to immune-modulating therapy, and for target pathways identification to generate novel drugs or therapeutic approaches. The final objective of immune monitoring is to find ways to improve the outcome of pancreas and islet transplantation. In this review, we discuss the available tools to monitor the innate, humoral and cellular responses after islet and pancreas transplantation, and the most relevant findings generated by these measurements.

Transplantation technologies for treatment of carbohydrate metabolism disorders

“…Степень его может быть косвенно выявлена и оценена по транзиторному повышению уровня АСТ и АЛТ, которое наблюдается у половины реципиентов и достигает пика к концу первой недели после ТОК. Системное влияние ИРП после ТОК выражено слабо, однако локально оно достоверно способствует ранней потере жизнеспособности островков [37,38]. Нативные островковые клетки очень хорошо оксигенируются, потребляя 5-15% кислорода, протекающего через поджелудочную железу, с напряжением кислорода около 40 мм рт.…”

Immunological aspects of allogeneic pancreatic islet transplantation: a comparison between mouse and human

“…Second, the alloimmune reaction is comparable in both species given that the same immune cells, such as DCs, T cells, and macrophages, are involved in islet allograft destruction. Islets express antigens such as insulin, IA‐2, GAD‐65, and ZnT8 that are highly antigenic and activate T‐ and B‐cell responses . These antigens are recognized by the host immune system through direct or indirect presentation.…”

“…Once the immune system is activated, macrophages, neutrophils, NK cells, granulocytes, DCs, B cells, CD4, and CD8 T cells migrate around the graft, drive a pro‐inflammatory cascade and graft destruction . CD8 T cells of the host can directly destroy islet cells and are considered together with CD4 T cells as the most important cell types to measure in order to predict graft outcome after islet transplantation . Mouse studies reveal that treatment with an anti‐CD3 antibody decreases the numbers of CD4 and CD8 T cells in the graft.…”

Autologous and Allogenous Antibodies in Lung and Islet Cell Transplantation

“…Autoantibodies in the circulation are formed during the pathogenesis of T1D prior to islet transplantation. Autoantibodies against pancreatic islets that are deemed clinically significant include anti-glutamate decarboxylase 65 (GAD65), anti-insulin autoantibody, anti-zinc transporter ZnT8, anti-islet cell autoantibody, and anti-tyrosine phosphatase autoantibody (IA-2) (102). Some of the earlier reports of posttransplant immune responses in islet transplant recipients suggested that no correlation existed between preexisting autoantibodies and islet graft failure (96, 98).…”