Zinc transporter 8 autoantibodies are a risk factor for type 1 diabetes recurrence in recipients of simultaneous pancreas kidney transplants.
Hopfner, Yan Yuh
Objective: Despite improved immunosuppression, a reactivation of islet autoimmunity and consequently recurrence of T1D (T1DR) cannot be prevented in type 1 diabetic (T1D) patients after simultaneous pancreas kidney (SPK) transplantation. Hence, diagnostic work-up of graft failure should include islet autoimmunity assessment pre and post transplantation. Previous analyses of GAD and IA-2 autoantibodies (AAb) in SPK recipients have shown a clear association with T1DR. In this study, we investigated, whether the appearance of ZnT8 AAb is also associated with the development of T1DR. Methods: We retrospectively measured ZnT8 AAb in serial samples obtained prior and post transplantation in 452 SPK recipients with a mean follow-up of 6.2 ± 4.1 years (range 1 - 22.6). The cohort consisted of 176 patients with normal glucose tolerance (NGT), 47 patients who developed hyperglycemia on follow-up, which included 17 T1DR, 10 with pancreas chronic rejection (PCR) and 20 of undetermined origin (UND). Results: Compared to GAD and IA-2 AAb, ZnT8 AAb was rarely found prior transplantation. However, on follow-up, ZnT8 AAb had stronger association with T1DR than GAD and IA-2 (ZnT8 OR = 17.9, p < 0.0001; GAD OR = 16.1, p < 0.0001 and IA-2 OR = 15.8, p < 0.0001). Specificity and positive predictive value (PPV) for T1DR were 0.68/0.21 (GADA), 0.83/0.30 (IA-2A) and 0.93/0.43 (ZnT8A). A higher number of AAb was associated with T1DR, with specificity/PPV values of 0.64/0.03 for 1 AAb, 0.88/0.30 for 2 AAb including ZnT8A (0.90/0.40 for 2 AAb without ZnT8) and 0.95/ 0.62 for 3 AAb. 47.1 % of our T1DR patients had 3 AAb compared to only 2.8 % of the normoglycemic patients (p = or < 0.0001, OR = 30.4). The value of adding ZnT8A and therefore measuring 3 AAb was also verified by Kaplan-Meier survival analysis. Conclusion: Including ZnT8 AAb leads to a significantly improved prediction of T1DR in SPK recipients and enhances the diagnostic and predictive power of AAb screening in SPK patients.
Subject HeadingsAutoantikörper [GND]
Diabetes mellitus, type 1 [MeSH]
KeywordsAutoantibody screening; GAD autoantibody; IA-2 autoantibody; Islet autoimmunity; Simultaneous pancreas kidney transplantation; ZnT8 autoantibody
Dewey Decimal GroupDDC 610 / Medicine & health
MetadataShow full item record
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