Background: Besides alloimmunity to transplanted pancreatic tissue, recurrent autoimmune beta cell destruction is an additional limitation to successful clinical pancreatic allografts in type 1 diabetic patients.
Methods: We studied the prevalence of autoantibodies to glutamate decarboxylase (GAD) 65 and tyrosine phosphatase (IA-2) in 68 C-peptide-negative diabetic patients receiving pancreatic allografts. Sera from patients were obtained immediately before grafting. A second blood sample was analyzed at the time of graft failure in patients who returned to hyperglycemia and during the same follow-up period in those who experienced a functional pancreatic allograft. Patients were classified according to clinical outcome into chronic graft failure (group A, n=20), acute graft failure and/or arterial thrombosis (n=7), or functional pancreatic graft (group C, n=41). Sera from patients were screened for the presence of specific autoantibodies using an islet cell autoantibody assay, a combi-GAD and IA-2 test, and individual GAD and IA-2 assays.
Results: Patients from group A had significantly higher combi-test values than patients from group C (13+/-16 vs. 4.5+/-12 units, P<0.02) and higher anti-GAD65 antibody (Ab) levels (0.19+/-0.3 vs. 0.04+/-0.13 units, P<0.01) immediately before grafting. After graft failure in group A, both anti-GAD65 and anti-IA-2 Ab levels increased from baseline, but only the increase in anti-IA-2 Ab levels reached statistical significance (0.28+/-0.12 vs. 15+/-34, P=0.03). When compared with group C, patients from group A had higher anti-GAD65 Abs (0.29+/-0.35 vs. 0.05+/-0.16, P<0.001) after graft failure. Interestingly, the number of double-Ab-positive patients rose from 5% to 35% in group A, whereas it remained at 5% in group C. In pancreatic transplants with bladder drainage, the presence of anti-GAD65 and/or anti-IA2 Abs was not associated with a reduction in urinary amylase levels. This suggests that a loss of endocrine function was not associated with exocrine failure in patients from group A.
Conclusions: We can conclude from the present study that peripheral autoimmune markers are useful in diabetic patients receiving pancreatic allografts.