2011 - IPITA - Prague


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Plenary session 6: Presidential session

6.4 - ZnT8 autoantibodies are associated with type 1 diabetes recurrence (T1DR) in simultaneous pancreas-kidney (SPK) transplant recipients

Presenter: G., Burke, Miami, USA
Authors: G. Burke, Y.Y. Kitvarametha, S. Diamantopoulos, G. Allende, F. Vendrame, I. Snowhite, J. Sageshima, L. Chen, G. Ciancio, P. Ruiz, H. Reijonen, J. Hutton, A. Pugliese


ZnT8 autoantibodies are associated with type 1 diabetes recurrence (T1DR) in simultaneous pancreas-kidney (SPK) transplant recipients

G. Burke1, Y.Y. Kitvarametha2, S. Diamantopoulos2, G. Allende2, F. Vendrame2, I. Snowhite2, J. Sageshima1, L. Chen1, G. Ciancio1, P. Ruiz1, H. Reijonen3, J. Hutton4, A. Pugliese2
1 University of Miami, Surgery, Miami, USA; 2 Diabetes Research Institute, University of Miami, Miami, USA; 3 Benaroya Research Institute, Seattle, USA; 4 Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver, USA

Objective: Earlier analysesof GAD and IA-2 autoantibodies (AAb) in our cohort of SPK recipients showedthat these are associated with the development of T1DR, especially whenappearing on follow-up in patients who were negative pre-transplant(conversion). We now investigated if Znt8 AAb are also associated with T1DR.

Methods: We retrospectively measured AAb associatedwith type 1 diabetes (GAD, IA-2 and ZnT8) in serial samples obtained prior toand following transplantation in 198 SPK recipients with a mean follow-up of 5.5+ 3.7 years (range 0.12-19). This cohort included 159 patients withnormal glucose tolerance (NGT) and 39 patients who developed hyperglycemia onfollow-up which was explained by T1DR (13), chronic rejection (12), or wasconsidered of undetermined origin (14).

Results: Comparedto GAD and IA-2 AAb, ZnT8 AAb were almost never found in NGT patients, thus showinga much stronger association with T1DR (ZnT8 OR=27.5, p<0.000001; GAD OR=8.8,p=0.002 and IA-2 OR= 3.5, p=0.03). None of the AAb were significantly associatedwith chronic rejection or undetermined hyperglycemia. Specificity and positivepredictive value (PPV) for T1DR were 0.72/0.20 (GAD), 0.83/0.22 (IA-2) and0.96/0.54 (ZnT8). A higher number of AAb was associated with T1DR, withspecificity/PPV values of 0.55/0.05 (1 AAb), 0.73/0.07 (2 AAb) and 0.95/0.64 (3AAb). Indeed, 54% of our T1DR patients had 3 AAb compared to only 2.5% of theNGT patients (p<0.000001, OR= 45). The value of adding ZnT8 AAb and thusmeasuring 3 AAb was also confirmed by Kaplan-Meier survival analysis.

Conclusions: Including ZnT8AAb leads to significantly improved prediction of T1DR in SPK recipients.


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