Serological markers of recurrent beta cell destruction in diabetic patients undergoing pancreatic transplantation

Background Besides alloimmunity to transplanted pancreatic tissue, recurren t autoimmune beta cell destruction is an additional limitation to successfu l clinical pancreatic allografts in type 1 diabetic patients. Methods. We studied the prevalence of autoantibodies to glutamate decarboxy lase (GAD) 65 and tyrosine phosphatase (IA-2) in 68 C-peptide-negative diab etic: patients receiving pancreatic allografts. Sera from patients were obt ained immediately before grafting, A. second blood sample was analyzed at t he time of graft failure in patients who returned to hyperglycemia and duri ng the same follow-up period in those who experienced a functional pancreat ic allograft. Patients were classified according to clinical outcome into c hronic graft failure (group A, n=20), acute graft failure and/or arterial t hrombosis (n=7), or functional pancreatic graft (group C, n=41). Sera from patients were screened for the presence of specific autoanti- bodies 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 t han patients from group C (13+/-16 vs. 4.5+/-12 units, P<0.02) and higher a nti-GAD65 antibody (Ab) levels (0.19+/-0.3 vs. 0.04+/-0.13 units, P<0.01) i mmediately before grafting. After graft failure in group A, both anti-GAD65 and anti-IA-a 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 a nti-GAD65 Abs (0.29+/-0.35 vs, 0.05+/-0.16, P<0.001) after graft failure, I nterestingly, the number of double-Ah-positive patients rose from 5% to 35% in group A, whereas it remained at 5% in group C. In pancreatic transplant s 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 t hat a loss of endocrine function was not associated with exocrine failure i n patients from group A, Conclusions. We can conclude from the present study that peripheral autoimm une markers are useful in diabetic patients receiving pancreatic allografts .