Immune Monitoring of Islet and Pancreas Transplant Recipients
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Type 1 diabetes (T1D) is an autoimmune disease in which the insulin-producing beta-cells are destroyed. Islet or pancreas transplantation can restore insulin secretion and are established therapies for subgroups of T1D patients. Long-term insulin-independence is, however, hampered by recurrent autoimmunity and rejection. Accurate monitoring of these immune events is therefore of critical relevance for the timely detection of deleterious immune responses. The identification of relevant immune biomarkers of allo- and autoreactivity has allowed a more accurate monitoring of disease progression and responses to therapy at early stages, allowing proper therapeutic intervention, and possibly improvements in the success rate of islet and pancreas transplantation. This review describes the tools established and validated to monitor immune correlates of auto- and alloreactivity that associate with clinical outcome and identifies challenges that current immunosuppression strategies trying to preserve islet graft function face.
KeywordsType 1 diabetes Autoimmune disease Islet transplantation Pancreas transplantation Immune monitoring Biomarkers
The authors were supported by grants from the Juvenile Diabetes Research Foundation, the Dutch Diabetes Research Foundation, ZonMW (VICI award) and the European Union FP7 Program (BetaCellTherapy and NAIMT).
Compliance with Ethics Guidelines
Conflict of Interest
Joana R. F. Abreu declares that she has no conflict of interest.
Bart O. Roep has board membership with Diamyd, Andromeda; has been a consultant for Novo Nordisk, GlaxoSmithKline.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 1.• Coppieters KT, Dotta F, Amirian N, Campbell PD, Kay TW, Atkinson MA, et al. Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients. J Exp Med. 2012;209:51–60. Ultimate proof that insulitis in human pancreatic leasions contain islet auoreactive CD8 T cells. PubMedCrossRefGoogle Scholar
- 10.• Vendrame F, Pileggi A, Laughlin E, Allende G, Martin-Pagola A, Molano RD, et al. Recurrence of type 1 diabetes after simultaneous pancreas-kidney transplantation, despite immunosuppression, is associated with autoantibodies and pathogenic autoreactive CD4 T-cells. Diabetes. 2010;59:947–57. First evidence that recuurent autoimmunity may be cause of chronic loss of function in pancreas allograft recipients. PubMedCrossRefGoogle Scholar
- 12.Piemonti L, Everly MJ, Maffi P, Scavini M, Poli F, Nano R, et al. Alloantibody and autoantibody monitoring predicts islet transplantation outcome in human type 1 Diabetes. Diabetes. 2012;62:1656–64.Google Scholar
- 14.• Huurman VA, Hilbrands R, Pinkse GG, Gillard P, Duinkerken G, van de Linde P, et al. Cellular islet autoimmunity associates with clinical outcome of islet cell transplantation. PLoS One. 2008;3:e2435. First evidence that cellular islet autoimmunity before transplantation determines outcome, rather than islet autoantibodies at baseline. Alloreactivity to the islet donor proved secondary to recurrent islet autoimmunity. PubMedCrossRefGoogle Scholar
- 17.• Monti P, Scirpoli M, Maffi P, Ghidoli N, de Taddeo F, Bertuzzi F, et al. Islet transplantation in patients with autoimmune diabetes induces homeostatic cytokines that expand autoreactive memory T cells. J Clin Invest. 2008;118:1806–14. Demonstration of homeostatic expansion by islet auoreactive memory CD8 T cells following debulking induction therapy with thymoglobulin before islet transplantation. PubMedGoogle Scholar
- 34.Stobbe I, Duinkerken G, van Rood JJ, Lernmark A, Keymeulen B, Pipeleers D, et al. Tolerance to kidney allograft transplanted into Type I diabetic patients persists after in vivo challenge with pancreatic islet allografts that express repeated mismatches. Diabetologia. 1999;42:1379–80.PubMedCrossRefGoogle Scholar
- 44.Alkemade GM, Clemente-Casares X, Yu Z, Xu BY, Wang J, Tsai S, et al. Local autoantigen expression as essential gatekeeper of memory T-cell recruitment to islet grafts in diabetic hosts. Diabetes. 2012;[In press].Google Scholar