TY - JOUR
T1 - Lessons From Pancreas Transplantation in Type 1 Diabetes
T2 - Recurrence of Islet Autoimmunity
AU - Burke, George W.
AU - Vendrame, Francesco
AU - Virdi, Sahil K.
AU - Ciancio, G.
AU - Chen, Linda
AU - Ruiz, Phillip
AU - Messinger, Shari
AU - Reijonen, Helena K.
AU - Pugliese, Alberto
N1 - Funding Information:
Studies by the authors reviewed here were supported by grants from the National Institutes of Health (R01 DK070011, R01 DK052068), the JDRF (17-2011-594, 17-2012-3), the American Diabetes Association (RA-1-09-RA-413), the John C. Hench Foundation, and the Diabetes Research Institute Foundation, Hollywood, Florida. We are indebted to our research nurses, Lissett Tueros, Lois Hanson, and Sandra Flores.
Publisher Copyright:
© 2015, Springer Science+Business Media New York.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - Type 1 diabetes recurrence (T1DR) affecting pancreas transplants was first reported in recipients of living-related pancreas grafts from twins or HLA identical siblings; given HLA identity, recipients received no or minimal immunosuppression. This observation provided critical evidence that type 1 diabetes (T1D) is an autoimmune disease. However, T1DR is traditionally considered very rare in immunosuppressed recipients of pancreas grafts from organ donors, representing the majority of recipients, and immunological graft failures are ascribed to chronic rejection. We have been performing simultaneous pancreas–kidney (SPK) transplants for over 25 years and find that 6–8 % of our recipients develop T1DR, with symptoms usually becoming manifest on extended follow-up. T1DR is typically characterized by (1) variable degree of insulitis and loss of insulin staining, on pancreas transplant biopsy (with most often absent), minimal to moderate and rarely severe pancreas, and/or kidney transplant rejection; (2) the conversion of T1D-associated autoantibodies (to the autoantigens GAD65, IA-2, and ZnT8), preceding hyperglycemia by a variable length of time; and (3) the presence of autoreactive T cells in the peripheral blood, pancreas transplant, and/or peripancreatic transplant lymph nodes. There is no therapeutic regimen that so far has controlled the progression of islet autoimmunity, even when additional immunosuppression was added to the ongoing chronic regimens; we hope that further studies and, in particular, in-depth analysis of pancreas transplant biopsies with recurrent diabetes will help identify more effective therapeutic approaches.
AB - Type 1 diabetes recurrence (T1DR) affecting pancreas transplants was first reported in recipients of living-related pancreas grafts from twins or HLA identical siblings; given HLA identity, recipients received no or minimal immunosuppression. This observation provided critical evidence that type 1 diabetes (T1D) is an autoimmune disease. However, T1DR is traditionally considered very rare in immunosuppressed recipients of pancreas grafts from organ donors, representing the majority of recipients, and immunological graft failures are ascribed to chronic rejection. We have been performing simultaneous pancreas–kidney (SPK) transplants for over 25 years and find that 6–8 % of our recipients develop T1DR, with symptoms usually becoming manifest on extended follow-up. T1DR is typically characterized by (1) variable degree of insulitis and loss of insulin staining, on pancreas transplant biopsy (with most often absent), minimal to moderate and rarely severe pancreas, and/or kidney transplant rejection; (2) the conversion of T1D-associated autoantibodies (to the autoantigens GAD65, IA-2, and ZnT8), preceding hyperglycemia by a variable length of time; and (3) the presence of autoreactive T cells in the peripheral blood, pancreas transplant, and/or peripancreatic transplant lymph nodes. There is no therapeutic regimen that so far has controlled the progression of islet autoimmunity, even when additional immunosuppression was added to the ongoing chronic regimens; we hope that further studies and, in particular, in-depth analysis of pancreas transplant biopsies with recurrent diabetes will help identify more effective therapeutic approaches.
KW - Autoantibodies
KW - Autoreactive T cells
KW - Islet autoimmunity
KW - Pancreas transplantation
KW - Recurrent diabetes
KW - Type 1 diabetes
UR - http://www.scopus.com/inward/record.url?scp=84946554983&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84946554983&partnerID=8YFLogxK
U2 - 10.1007/s11892-015-0691-5
DO - 10.1007/s11892-015-0691-5
M3 - Review article
C2 - 26547222
AN - SCOPUS:84946554983
VL - 15
SP - 1
EP - 9
JO - Current Diabetes Reports
JF - Current Diabetes Reports
SN - 1534-4827
IS - 12
M1 - 121
ER -