Reactivation of type 1 diabetes in patients receiving human fetal pancreatic tissue transplants without immunosuppression.
BACKGROUND
Insulin-dependent (type 1) diabetes is a cell-mediated autoimmune disease. Successful transplantation of human fetal pancreatic tissue into type 1 diabetic patients must address both autoimmunity and allograft rejection. We investigated whether humoral and cellular responses to islet antigens could be demonstrated in the peripheral blood of type 1 diabetic subjects receiving human fetal pancreatic tissue transplants.


METHODS
We investigated peripheral blood mononuclear cell (PBMC) responses, using cellular immunoblotting, and autoantibody responses to islet proteins, before transplantation and at 3-month intervals after transplantation. Our study population included nine long-term type 1 diabetes patients (mean disease duration of 21 years) receiving human fetal pancreatic tissue subcutaneously into the abdominal wall without immunosuppression.


RESULTS
Before transplantation, all nine subjects tested negative for islet cell autoantibody (ICA), and seven of nine subjects tested positive for glutamic acid decarboxylase autoantibody (GADAb). After transplantation, all subjects became ICA(+), and the two patients who were GADAb(-) before transplantation, became GADAb(+) after transplantation. Maximum PBMC reactivity to separated human fetal pancreatic proteins was observed in four patients at 3 months, in one patient at 6 months, in two patients at 9 months, and in one patient at 12 months after transplantation. One subject, who had PBMC reactivity to multiple islet proteins before transplantation, continued to respond to multiple islet proteins throughout the study.


CONCLUSIONS
We conclude that the development in the peripheral blood of ICA, GADAb, and PBMC reactivity to human fetal pancreatic proteins in the transplant recipients is most consistent with reactivation of the type 1 diabetes disease process.
Brooks-Worrell
B M
BM
Department of Medicine, DVA Puget Sound Health Care System, Seattle, Washington 98108, USA.
Peterson
K P
KP
Peterson
C M
CM
Palmer
J P
JP
Jovanovic
L
L
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000032:analysis; D002455:Cell Division / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology* / Q000601:surgery*; D005260:Female; D005326:Fetal Proteins / Q000502:physiology; D016332:Fetal Tissue Transplantation; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology; D010179:Pancreas / Q000166:cytology / Q000196:embryology; D016035:Pancreas Transplantation
D001323:Autoantibodies; D005326:Fetal Proteins; C024211:islet cell antibody; D005968:Glutamate Decarboxylase