Abstract

BackgroundAutoantibodies to β-cell specific antigens are markers of type 1 diabetes. The most recently identified autoantibodies are targeted to the zinc transporter 8 (ZnT8) protein located in the membrane of β-cell insulin secretory granules. The prevalence of ZnT8 autoantibodies in newly diagnosed participants with type 1 diabetes has been found to range from 33 to 80 %. Due to the lack of data on the immunological aetiology of type 1 diabetes in African populations, this study aimed to determine the prevalence of ZnT8 autoantibodies in black South Africans with type 1 diabetes and whether ZnT8 autoantibody positivity was associated with age at diagnosis and disease duration.MethodsParticipants with type 1 diabetes and controls were recruited from the greater Johannesburg area, South Africa. Positivity for ZnT8, GAD65 and IA2 autoantibodies was determined by ELISA.ResultsParticipants with type 1 diabetes (n = 183) and controls (n = 49) were matched for age (29.1 ± 9.53 vs. 27.3 ± 7.29, respectively; p = 0.248). The mean age at diagnosis for participants with type 1 diabetes was 20.8 ± 8.46 years. The prevalence of ZnT8 autoantibody positivity was 17.5 % (32 of 183) in participants with type 1 diabetes with a median disease duration of 7.00 [2.00; 11.0] years. ZnT8 autoantibody prevalence in newly diagnosed participants (< 1 year duration) was 27.3 % (6 of 22). Logistic regression analysis found an association between ZnT8 autoantibody positivity and shorter disease duration (OR: 0.9 (0.81-1.00); p = 0.042). In addition, ZnT8 autoantibody positivity was significantly associated with an increased chance of being GAD65 (OR: 3.37 (1.10–10.3)) and IA2 (OR: 8.63 (2.82–26.4)) autoantibody positive. Multiple regression analysis found no association between ZnT8 autoantibody positivity and age at diagnosis. However, the presence of ≥ 2 autoantibodies was associated with a younger age at diagnosis of type 1 diabetes when compared to participants with ≤ 1 autoantibody (B = -5.270; p = 0.002).ConclusionsThe presence of ZnT8 autoantibodies was not related to a younger age at diagnosis in black South African patients with type 1 diabetes. However, the greater the numbers of autoantibodies present in an individual the earlier the age at diagnosis. ZnT8 autoantibodies decline with disease duration in the black South African population.

Highlights

  • IntroductionThe most recently identified autoantibodies are targeted to the zinc transporter 8 (ZnT8) protein located in the membrane of β-cell insulin secretory granules

  • Autoantibodies to β-cell specific antigens are markers of type 1 diabetes

  • Autoantibodies directed to the zinc transporter 8 (ZnT8) peptide have been described in Type 1 diabetes (T1D) [4]

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Summary

Introduction

The most recently identified autoantibodies are targeted to the zinc transporter 8 (ZnT8) protein located in the membrane of β-cell insulin secretory granules. The prevalence of ZnT8 autoantibodies in newly diagnosed participants with type 1 diabetes has been found to range from 33 to 80 %. Autoantibodies directed to the zinc transporter 8 (ZnT8) peptide have been described in T1D [4] This peptide is encoded by the SLC308 gene located on chromosome 8q24.11 and is found in the membrane of insulin secretory granules located in pancreatic β-cells [5]. In Europeans, the prevalence of ZnT8 AAbs ranged between 60 and 80 % of newly diagnosed participants with T1D [4, 8,9,10,11]. The T1D Genetics Consortium found that in newly diagnosed non-Hispanic black participants (duration < 3 years) the ZnT8 prevalence was 57.9 % (Wenzlau et al, 2015)

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