ISLET-CELL ANTIBODIES AND GLUTAMIC-ACID DECARBOXYLASE ANTIBODIES IN PATIENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS UNDERGOING KIDNEY ANDISLET-AFTER-KIDNEY TRANSPLANTATION

The humoral immune response to islet autoantigens, here defined by the presence of islet cell antibodies (ICA) and glutamic acid decarboxyla se (GAD 65) anti-bodies, was studied ill patients with long-term insul in-dependent diabetes mellitus (IDDM) receiving immunosuppressive ther apy following kidney and islet-after-kidney transplantation, In a cros s-sectional study of 30 kidney-grafted long-term IDDM patients and 30 matched, nontransplanted IDDM controls, we observed a significant (P<0 .05) decrease in ICA positivity by standard immunosuppressive therapy, but not in frequency or index levels of GAD 65 antibodies, Because of this intriguing finding we investigated in a pilot study on seven isl et-after-kidney transplant recipients, the time course of frequency an d levels of ICAs and GAD 65 antibodies relative to islet graft functio n, Stable islet graft function was seen in the patients with low GAD 6 5 antibody index levels, whereas rapid islet graft failure occurred in a patient with high GAD 65 antibody index levels prior to transplanta tion In addition, GAD 65 autoimmunity reoccurred in one pretransplant antibody-negative patient 2 months after graft failure was noted. In c onclusion, these observations suggest that beta-cell autoimmunity dire cted to GAD 65 can persist despite immunosuppressive therapy and may a dversely affect islet graft function, possibly indicating disease recu rrence as a major threat to successful clinical islet transplantation.