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]
Summary
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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