ZnT8 and type 1 diabetes [Review]

Kawasaki, Eiji

doi:10.1507/endocrj.ej12-0069

Cited by 55 publications

(46 citation statements)

References 28 publications

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“…Zinc transporters control its homoeostasis. ZnT8 is localised on insulin-containing secretory granule membranes (30). We still do not know whether the same process could be responsible for the development of thyroiditis and share polymorphisms in the SLC30A8 gene.…”

Section: Discussionmentioning

confidence: 99%

Are zinc transporter type 8 antibodies a marker of autoimmune thyroiditis in non-obese adults with new-onset diabetes?

Rogowicz-Frontczak

Zozulińska‐Ziółkiewicz

Litwinowicz

et al. 2014

European Journal of Endocrinology

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Objective: The diagnosis of autoimmune diabetes in non-obese adults is based on the detection of glutamic acid decarboxylase autoantibodies (GADA), islet cell antibodies (ICA) and antibodies to tyrosine phosphatase (IA-2A). Zinc transporter 8 (ZnT8) has been identified as a new autoantigen in patients with type 1 diabetes mellitus. The coincidence of autoimmune thyroiditis (AITD) with diabetes is common; therefore, screening of TSH and thyroid peroxidase antibodies (ATPO) is recommended during the diagnosis of diabetes. In this study, we determined whether the occurrence of islet autoantibodies is associated with a positive titre of ATPO in newly diagnosed adult-onset autoimmune diabetic patients. Results: In the study population, 70% (nZ56) of the subjects were positive for at least one of the four assessed markers of autoimmune diabetes (83.9% GADA, 62.5% ICA, 42.8% IA-2A and 33% ZnT8A) and 37.5% of the subjects were positive for ATPO. The ZnT8A-positive subjects had higher ATPO titres than the ZnT8A-negative subjects (172.7 (IQR: 0.36-410.4) vs 92.4 (IQR: 0-23.7) IU/ml, PZ0.001). Based on the assessed islet autoantibodies, the occurrence of positive ZnT8A and GADA was found to be related to a positive titre of ATPO using logistic regression (ORZ5.48, 95% CI: 1.65-18.14, PZ0.006 and ORZ3.42, 95% CI: 1.09-10.71, PZ0.03 respectively). Conclusions: In non-obese adults with new-onset diabetes, the presence of GADA and especially ZnT8 autoantibodies increases the risk of AITD.

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Section: Discussionmentioning

confidence: 99%

Are zinc transporter type 8 antibodies a marker of autoimmune thyroiditis in non-obese adults with new-onset diabetes?

Rogowicz-Frontczak

Zozulińska‐Ziółkiewicz

Litwinowicz

et al. 2014

European Journal of Endocrinology

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“…Zinc is necessary for structural stability of stored insulin in the β-cells. In pancreatic β-cells, the transport of zinc into the cytoplasm and insulin secretory granules is accomplished by ZnT8 [56] and ZnT8 Ab is one of the major markers for T1DM [57]. A possible association between ZnT8 expression in different tissues and metabolic control in experimental animals has been reported.…”

Section: Discussionmentioning

confidence: 99%

Organ-specific autoimmunity in relation to clinical characteristics in children with long-lasting type 1 diabetes

Głowińska‐Olszewska

Michalak

Łuczyński

et al. 2016

Journal of Pediatric Endocrinology and Metabolism

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Background: The aim of this study was to assess the prevalence of diabetes and other organ-specific autoantibodies (Ab) associated with various autoimmune conditions, in Polish children with type 1 diabetes mellitus (T1DM). Methods: In this study 114 patients, aged 13.4 years, with mean diabetes duration 5.2 years were included. Ab to islet cell antigens: glutamic acid decarboxylase (GAD), insulinoma antigen 2 (IA-2), zinc transporter 8 (ZnT8), together with thyroid peroxidase Ab (TPO Ab), thyroglobulin Ab (Tg Ab), tissue transglutaminase Ab (tTG Ab) and 21-hydroxylase Ab (21-OH Ab) were measured. Results: The prevalence of at least one diabetes associated Ab was found in 87%, with the highest prevalence of 64% for ZnT8 Ab. In patients with disease duration < 5 years, at least one antibody was present in 90%, the most prevalent was ZnT8 Ab (72%). In patients with duration > 10 years, 50% had at least one antibody. The prevalence of other than islet cell autoimmunity was high (34%). Thyroid Ab were detected in 26% patients, 42% in girls vs. 8% in boys, p < 0.001. tTG Ab were found in 11% patients, with a greater prevalence in children with early onset (p = 0.01). 21-OH Ab were found in 2.6% T1DM patients.

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“…Wenzlau et al followed the individuals from birth to T1D onset and they found that ZnT8 antibodies (ZnT8A) appeared as early as 2 years of age and showed increasing levels and prevalence persisting to disease onset (Wenzlau et al, 2009;Wenzlau et al, 2007). Some suggested a strong inverse relationship between the age of T1D onset and the prevalence of ZnT8A (Kawasaki, 2012). Our study demonstrated that ZnT8 as a novel autoantigen containing many immunodominant epitopes, which were recognized in type 1 diabetes patients (Xu et al, 2015).…”

Section: Introductionmentioning

confidence: 50%

“…As described in some articles, ZnT8 antigen, encoded by the gene SLC30A8, is a major autoantigen in T1D (Kawasaki, 2012). SLC30A8 gene is located on chromosome 8 at the position q24.11 in human.…”

Section: Discussionmentioning

confidence: 99%

Screening and identification of human ZnT8-specific single-chain variable fragment (scFv) from type 1 diabetes phage display library

Wang

et al. 2016

Sci. China Life Sci.

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Zinc transporter 8 (ZnT8) is a major autoantigen and a predictive marker in type 1 diabetes (T1D). To investigate ZnT8-specific antibodies, a phage display library from T1D was constructed and single-chain antibodies against ZnT8 were screened and identified. Human T1D single-chain variable fragment (scFv) phage display library consists of approximately 110 8 clones. After four rounds of bio-panning, seven unique clones were positive by phage ELISA. Among them, C27 and C22, which demonstrated the highest affinity to ZnT8, were expressed in Escherichia coli Top10F' and then purified by affinity chromatography. C27 and C22 specifically bound ZnT8 N/C fusion protein and ZnT8 C terminal dimer with one Arg325Trp mutation. The specificity to human islet cells of these scFvs were further confirmed by immunohistochemistry. In conclusion, we have successfully constructed a T1D phage display antibody library and identified two ZnT8-specific scFv clones, C27 and C22. These ZnT8-specific scFvs are potential agents in immunodiagnostic and immunotherapy of T1D.Zinc transporter 8 (ZnT8), phage display, single-chain variable fragment (scFv), type 1 diabetes (T1D) Citation:Wu, Q., Wang, X., Gu, Y., Zhang, X., Qin, Y., Chen, H., Xu, X., Yang, T., and Zhang, M. (2016). Screening and identification of human ZnT8-specific single-chain variable fragment (scFv) from type 1 diabetes phage display library. Sci China Life Sci 59, 686 -693.

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ZnT8 and type 1 diabetes [Review]

Cited by 55 publications

References 28 publications

Are zinc transporter type 8 antibodies a marker of autoimmune thyroiditis in non-obese adults with new-onset diabetes?

Are zinc transporter type 8 antibodies a marker of autoimmune thyroiditis in non-obese adults with new-onset diabetes?

Organ-specific autoimmunity in relation to clinical characteristics in children with long-lasting type 1 diabetes

Screening and identification of human ZnT8-specific single-chain variable fragment (scFv) from type 1 diabetes phage display library

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