Serological markers of recurrent beta cell destruction in diabetic patients undergoing pancreatic transplantation.
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.
Thivolet
C
C
INSERM 449, Faculty of Medicine RTH Laënnec, Lyon, France. c.thivolet@chu-lyon.fr
Abou-Amara
S
S
Martin
X
X
Lefrancois
N
N
Petruzzo
P
P
McGregor
B
B
Bosshard
S
S
Dubernard
J M
JM
D000328:Adult; D000681:Amylases / Q000652:urine; D001323:Autoantibodies / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D002096:C-Peptide / Q000172:deficiency; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology* / Q000601:surgery* / Q000652:urine; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000473:pathology*; D007527:Isoenzymes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000503:physiopathology; D016035:Pancreas Transplantation / Q000276:immunology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000276:immunology; D012008:Recurrence; D017211:Treatment Failure; D016896:Treatment Outcome
D001323:Autoantibodies; D015415:Biomarkers; D002096:C-Peptide; D007527:Isoenzymes; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D000681:Amylases; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2