Kinetics of the Post-Onset Decline in Zinc Transporter 8 Autoantibodies in Type 1 Diabetic Human Subjects

Wenzlau, Janet M.; Walter, Melanie; Gardner, Thomas J.; Frisch, Lisa M.; Yu, Liping; Eisenbarth, George S.; Ziegler, Anette‐G.; Davidson, Howard W.; Hutton, John C.

doi:10.1210/jc.2010-0169

Cited by 60 publications

(60 citation statements)

References 34 publications

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“…A concurrent decline in stimulated C-peptide and ZnT8Ab titers (Figure 3) was also previously found in a smaller type 1 diabetes population (n=21), neither of the two studies found a correlation between ZnT8Ab and residual beta-cell function during the study period [17]. In our study, ZnT8Ab's at 1 month did not predict residual betacell function at 12 months, although we did find that the level of IAA and GADA at 1 month after diagnosis was associated with a more rapid loss of residual beta cell function.…”

Section: Discussionsupporting

confidence: 79%

Relationship between ZnT8Ab, theSLC30A8gene and disease progression in children with newly diagnosed type 1 diabetes

Nielsen¹,

Vaziri-Sani²,

Pörksen³

et al. 2011

Autoimmunity

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Section: Discussionsupporting

confidence: 79%

Relationship between ZnT8Ab, theSLC30A8gene and disease progression in children with newly diagnosed type 1 diabetes

Nielsen¹,

Vaziri-Sani²,

Pörksen³

et al. 2011

Autoimmunity

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“…In our study, ZnT8A were only detected with the high‐risk conversion pattern. Similar to prospective studies of relatives and patients 43, 44, ZnT8A were the last autoantibodies to become positive on follow‐up, positivity was short lived, and their appearance was much closer to the development of diabetes symptoms (0.66 years vs. 2.27 and 3.63 years for GADA and IA‐2A, respectively). Thus, ZnT8A positivity raises the concern that diabetes recurrence may occur in the near future.…”

Section: Discussionsupporting

confidence: 63%

Risk Factors for Type 1 Diabetes Recurrence in Immunosuppressed Recipients of Simultaneous Pancreas–Kidney Transplants

Vendrame

Hopfner

Diamantopoulos

et al. 2016

American Journal of Transplantation

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Patients with type 1 diabetes (T1D) who are recipients of pancreas transplants are believed to rarely develop T1D recurrence in the allograft if effectively immunosuppressed. We evaluated a cohort of 223 recipients of simultaneous pancreas–kidney allografts for T1D recurrence and its risk factors. With long‐term follow‐up, recurrence was observed in approximately 7% of patients. Comparing the therapeutic regimens employed in this cohort over time, lack of induction therapy was associated with recurrence, but this occurs even with the current regimen, which includes induction; there was no influence of maintenance regimens. Longitudinal testing for T1D‐associated autoantibodies identified autoantibody positivity, number of autoantibodies, and autoantibody conversion after transplantation as critical risk factors. Autoantibodies to the zinc transporter 8 had the strongest and closest temporal association with recurrence, which was not explained by genetically encoded amino acid sequence donor–recipient mismatches for this autoantigen. Genetic risk factors included the presence of the T1D‐predisposing HLA‐DR3/DR4 genotype in the recipient and donor–recipient sharing of HLA‐DR alleles, especially HLA‐DR3. Thus, T1D recurrence is not uncommon and is developing in patients treated with current immunosuppression. The risk factors identified in this study can be assessed in the transplant clinic to identify recurrent T1D and may lead to therapeutic advances.

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“…In young patients with new-onset T1DM (53 ), 63% were positive for ZnT8A (vs 72% positive for GADA, 68% positive for IA-2A, and 55% positive for IAA). Following the onset of T1DM, ZnT8A concentrations decline rapidly (54,55 ).…”

Section: What Islet Autoantibody Determinations Are Available For CLImentioning

confidence: 99%

Autoimmune Markers in Diabetes

2011

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BACKGROUND: Type 1 diabetes (T1DM) results from cell-mediated autoimmune destruction of the ␤ cells of the islets of Langerhans. Autoantibodies directed against the islets are useful clinical tools that allow the recognition and confirmation of ␤-cell autoimmunity.CONTENT: In this review we define the term "islet autoantibody," describe the pathogenesis of autoantibody generation, and explain the uses of islet autoantibodies in clinical medicine and in research studies that concern the interruption or prevention of T1DM. We also discuss the biology of islet autoantibodies and their rates of appearance at the time of onset of T1DM and their appearance before the development of T1DM.

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Kinetics of the Post-Onset Decline in Zinc Transporter 8 Autoantibodies in Type 1 Diabetic Human Subjects

Abstract: ZnT8 humoral autoreactivity declines rapidly in the first years after disease onset and is less persistent than IA2A or GADA in the longer term. ZnT8A determination may be a useful measure of therapeutic efficacy in the context of immune-based clinical interventions.

Cited by 60 publications

References 34 publications

Relationship between ZnT8Ab, theSLC30A8gene and disease progression in children with newly diagnosed type 1 diabetes

Relationship between ZnT8Ab, theSLC30A8gene and disease progression in children with newly diagnosed type 1 diabetes

Risk Factors for Type 1 Diabetes Recurrence in Immunosuppressed Recipients of Simultaneous Pancreas–Kidney Transplants

Autoimmune Markers in Diabetes

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