Association of Zinc Transporter-8 Autoantibody (ZnT8A) with Type 1 Diabetes Mellitus

Abstract

Background: Zinc transporter 8 autoantibody (ZnT8A), discovered through bioinformatics, is identified as another major biomarker for type 1 diabetes mellitus (T1DM), expanding the panel of diagnostic autoantibodies. The absence of standard autoantibodies in T1DM patients and the presence of ZnT8A in individuals before disease development has led the researchers to evaluate ZnT8A to gather information about the frequency and its association. Therefore, we aim to find out the concentration of ZnT8A and its association with T1DM. Methods: A case-control study with 25 type 1 diabetes mellitus patients and 25 first-degree relatives of cases as controls was conducted at Ziauddin University in collaboration with the Baqai Institute of Diabetology and Endocrinology (BIDE), Karachi. Demographic data were collected from patients on a standard questionnaire. Blood samples were collected, after approval from Ziauddin Ethics Review Committee, from subjects and serum was separated to estimate ZnT8A by using sandwich enzyme-linked immunosorbent assay (ELISA). Results: The mean age at diagnosis of T1DM patients was 13.40±5.05 years, and the duration of diabetes was 7.74±5.85 years. The frequency of ZnT8A was found higher in cases (19 (76%)) compared to controls (6 (24%)). ZnT8A concentrations were significantly higher in cases (13.82 ng/ml) compared to the controls (8.78 ng/ml; p= 0.024). The cutoff value of 9 ng/ml was selected for measuring sensitivity, specificity, and accuracy, which were determined as 76%, 76%, and 76%, respectively. Conclusions: ZnT8A was found significantly associated with T1DM. Subjects with ZnT8A values ≥ 9 ng/ml are 10 times more at risk to develop T1DM (p = 0.000).

Mechanism of Zn2+ and Ca2+ Binding to Human S100A1

“…In addition, S100A1, together with amyloid peptides, was detected in the aqueous humor of glaucoma patients [ 8 , 9 ]. S100A1 expression is dysregulated in type I diabetes, which is characterized by altered Zn 2+ homeostasis [ 63 , 64 , 65 ]. Furthermore, the upregulation of S100A1 is found in tumors such as melanoma (> 100-fold increase), renal cell carcinoma and ovarian cancer [ 65 , 66 , 67 , 68 ].…”

β-cell self-destruction and extremely complicated and still unknown etiopathogenesis of type 1 diabetes

“…Islet cell antibodies (ICA) are detected in patients diagnosed with type 1 diabetes, moreover in first-degree relatives of diabetic patients, months or years before the onset of clinical symptoms [25]. Recently, Bhatty et al presented the results of studies on the titre of ZnT8A autoantibodies in adolescents with Type 1 diabetes and their first degree relatives [26]. They found a significant association of ZnT8A titer with the development of type 1 diabetes.…”

“…Recently, Bhatty et al . presented the results of studies on the titre of ZnT8A autoantibodies in adolescents with Type 1 diabetes and their first degree relatives [ 26 ]. They found a significant association of ZnT8A titer with the development of type 1 diabetes.…”

“…They found a significant association of ZnT8A titer with the development of type 1 diabetes. According to the authors, patients with ZnT8A values ≥ 9 ng/ml are 10 times more likely to develop type 1 diabetes [ 26 ]. Similar observations on the role of the ZnT8A autoantibody were recently presented by Kawasaki et al .…”

Peptidome Analysis of Pancreatic Tissue Derived from T1DM Mice: Insights into the Pathogenesis and Clinical Treatments of T1DM

“…In recent years, the global incidence of T1DM has increased rapidly. It is estimated to account for 5-10% of all diabetes cases worldwide and is expected to surge by 3% per year [3]. The etiology and pathogenesis of T1DM are complex and have not been fully elucidated up to now.…”