A significant role for histocompatibility in human islet transplantation.
BACKGROUND
In recent years, transplantation of islets and pancreas has become a viable option for patients debilitated with type I diabetes. The success of islet transplantation has been attributed to the ability to isolate high quality islets for transplantation and capacity to maintain the recipient's immunosuppressive levels within a specific target range following transplantation. The purpose of this study was to determine the role of pretransplant sensitization to human leukocyte antigen (HLA) in islet transplantation.


METHODS
We retrospectively analyzed seven patients that were transplanted with islets under the auspices of the Juvenile Diabetes Research Foundation and Islet Cell Resource Center/National Institutes of Health. Humoral sensitization towards donor antigens both prior to and following islet transplantation was detected by FLOW panel reactive antibodies (PRA) and donor-specific cellular sensitization was detected by performing enzyme-linked immunospot assay analysis for cytokines interferon-gamma and interleukin-2.


RESULTS
Our analysis demonstrates that humoral and cellular sensitization to histocompatibility antigens prior to and after islet transplantation are associated with the failure of transplanted islets


CONCLUSIONS
Patient selection based on sensitization to donor HLA may be one of the factors crucial for the success of islet transplant. Further, in some patients, rejection of islets can be associated with sensitization to mismatched donor histocompatibility antigens.
Mohanakumar
T
T
Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA. kumart@wustl.edu
Narayanan
Kishore
K
Desai
Niraj
N
Ramachandran
Sabarinathan
S
Shenoy
Surendra
S
Jendrisak
Martin
M
Susskind
Brian M
BM
Olack
Barbara
B
Benshoff
Nicholas
N
Phelan
Donna L
DL
Brennan
Daniel C
DC
Fernandez
Luis A
LA
Odorico
Jon S
JS
Polonsky
Kenneth S
KS
D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000601:surgery*; D006680:HLA Antigens / Q000276:immunology; D006648:Histocompatibility / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007328:Insulin / Q000097:blood; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D006680:HLA Antigens; D007328:Insulin