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Emanuele Bosi - One of the best experts on this subject based on the ideXlab platform.
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Zinc Transporter 8 autoantibodies increase the predictive value of islet autoantibodies for function loss of technically successful solitary pancreas transplant.
Transplantation, 2011Co-Authors: Margherita Occhipinti, Vito Lampasona, Fabio Vistoli, Elena Bazzigaluppi, Marina Scavini, Ugo Boggi, Piero Marchetti, Emanuele BosiAbstract:BACKGROUND Despite the success rate of solitary pancreas transplantation in type 1 diabetes with preserved kidney function has greatly improved in recent years, a residual proportion of failures persists. METHODS With the aim of investigating autoimmunity as an unrecognized cause of graft failure, we measured autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A) and the recently discovered Zinc Transporter 8 antigen (ZnT8A) in 25 recipients of technically successful solitary pancreas transplantation. RESULTS The overall pancreas graft survival was 92%, 88%, and 80% at 2, 4, and 6 years, respectively. Fourteen patients (56%) had one or more autoantibodies before transplantation, with no effect on subsequent pancreas graft outcome. After transplantation, major autoantibody changes (serum conversion from negative to positive, spreading from one to multiple autoantibodies, or titer increase) were observed in 5 of 25 recipients: in four patients, the autoantibody change was followed by the loss of graft function (95% sensitivity, 80% positive predictive value), with a significantly lower graft survival compared with patients without autoantibodies (P
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Zinc Transporter 8 autoantibodies increase the predictive value of islet autoantibodies for function loss of technically successful solitary pancreas transplant
Transplantation, 2011Co-Authors: Margherita Occhipinti, Vito Lampasona, Fabio Vistoli, Elena Bazzigaluppi, Marina Scavini, Ugo Boggi, Piero Marchetti, Emanuele BosiAbstract:BACKGROUND Despite the success rate of solitary pancreas transplantation in type 1 diabetes with preserved kidney function has greatly improved in recent years, a residual proportion of failures persists. METHODS With the aim of investigating autoimmunity as an unrecognized cause of graft failure, we measured autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A) and the recently discovered Zinc Transporter 8 antigen (ZnT8A) in 25 recipients of technically successful solitary pancreas transplantation. RESULTS The overall pancreas graft survival was 92%, 88%, and 80% at 2, 4, and 6 years, respectively. Fourteen patients (56%) had one or more autoantibodies before transplantation, with no effect on subsequent pancreas graft outcome. After transplantation, major autoantibody changes (serum conversion from negative to positive, spreading from one to multiple autoantibodies, or titer increase) were observed in 5 of 25 recipients: in four patients, the autoantibody change was followed by the loss of graft function (95% sensitivity, 80% positive predictive value), with a significantly lower graft survival compared with patients without autoantibodies (P<0.0001). The addition of ZnT8A to GADA and IA-2A increased the number of identified autoantibody changes from three to five of 25 recipients and the number of predicted graft function loss from two to four out of five graft losses. CONCLUSIONS Detection of major autoantibody changes after technically successful solitary pancreas transplantation is predictive of subsequent loss of graft function. ZnT8A in addition to GADA and IA-2A are a useful marker to be included in the screening panel of posttransplant immune monitoring.
Vito Lampasona - One of the best experts on this subject based on the ideXlab platform.
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autoantibodies against Zinc Transporter 8 further stratify the autoantibody defined risk for type 1 diabetes in a general population of schoolchildren and have distinctive isoform binding patterns in different forms of autoimmune diabetes results fro
Diabetic Medicine, 2021Co-Authors: K Baumann, Vito Lampasona, K Kesselring, U. Walschus, Wolfgang Kerner, Ralf Wassmuth, M SchlosserAbstract:Aims To evaluate the diagnostic relevance of autoantibodies against Zinc Transporter 8 (ZnT8) in schoolchildren from the general population as well as in people with autoimmune diabetes. Methods A total of 137 schoolchildren positive for at least one of the three major diabetes-associated autoantibodies, without diabetes heredity or preselection on HLA typing, from the Karlsburg Type 1 Diabetes Risk Study, as well as 102 people at type 1 diabetes onset, 88 people with latent autoimmune diabetes in adults and 119 people with type 2 diabetes, were analysed for different ZnT8 autoantibody variants. Results Zinc Transporter 8 autoantibody positivity was found in 18% of autoantibody-positive schoolchildren, with a noticeable association with other autoantibodies associated with type 1 diabetes and disease progression. Furthermore, ZnT8 autoantibody positivity was associated with diabetes progression in schoolchildren positive for autoantibodies against insulinoma-associated antigen-2 (IA-2) and, importantly, in seven IA-2 autoantibody-negative schoolchildren. Additionally, ZnT8 autoantibodies were found in 56% of people with type 1 diabetes, predominantly directed against all three ZnT8 variants and comparable to schoolchildren with multiple autoantibodies. In contrast, ZnT8 autoantibodies were detected in 10% of people with latent autoimmune diabetes in adults, none of them with reactivity to all three isoforms. Conclusion Zinc Transporter 8 autoantibodies are useful markers for prediction of type 1 diabetes in a general population, further stratifying the risk of progression in autoantibody-positive children. ZnT8 autoantibodies are also important markers in adult-onset diabetes, with a completely different reaction pattern in type 1 diabetes in comparison to latent autoimmune diabetes in adults, and may therefore help to differentiate between the two forms.
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Autoantibodies against Zinc Transporter 8 further stratify the autoantibody‐defined risk for type 1 diabetes in a general population of schoolchildren and have distinctive isoform binding patterns in different forms of autoimmune diabetes: results fr
Diabetic medicine : a journal of the British Diabetic Association, 2020Co-Authors: K Baumann, Vito Lampasona, K Kesselring, U. Walschus, Wolfgang Kerner, Ralf Wassmuth, Michael SchlosserAbstract:Aims To evaluate the diagnostic relevance of autoantibodies against Zinc Transporter 8 (ZnT8) in schoolchildren from the general population as well as in people with autoimmune diabetes. Methods A total of 137 schoolchildren positive for at least one of the three major diabetes-associated autoantibodies, without diabetes heredity or preselection on HLA typing, from the Karlsburg Type 1 Diabetes Risk Study, as well as 102 people at type 1 diabetes onset, 88 people with latent autoimmune diabetes in adults and 119 people with type 2 diabetes, were analysed for different ZnT8 autoantibody variants. Results Zinc Transporter 8 autoantibody positivity was found in 18% of autoantibody-positive schoolchildren, with a noticeable association with other autoantibodies associated with type 1 diabetes and disease progression. Furthermore, ZnT8 autoantibody positivity was associated with diabetes progression in schoolchildren positive for autoantibodies against insulinoma-associated antigen-2 (IA-2) and, importantly, in seven IA-2 autoantibody-negative schoolchildren. Additionally, ZnT8 autoantibodies were found in 56% of people with type 1 diabetes, predominantly directed against all three ZnT8 variants and comparable to schoolchildren with multiple autoantibodies. In contrast, ZnT8 autoantibodies were detected in 10% of people with latent autoimmune diabetes in adults, none of them with reactivity to all three isoforms. Conclusion Zinc Transporter 8 autoantibodies are useful markers for prediction of type 1 diabetes in a general population, further stratifying the risk of progression in autoantibody-positive children. ZnT8 autoantibodies are also important markers in adult-onset diabetes, with a completely different reaction pattern in type 1 diabetes in comparison to latent autoimmune diabetes in adults, and may therefore help to differentiate between the two forms.
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Diabetes Antibody Standardization Program: First Proficiency Evaluation of Assays for Autoantibodies to Zinc Transporter 8
Clinical chemistry, 2011Co-Authors: Vito Lampasona, Janet M Wenzlau, John C Hutton, Peter Achenbach, Alistair J K Williams, Michael Schlosser, Patricia W. Mueller, Participating LaboratoriesAbstract:BACKGROUND: Zinc Transporter 8 (ZnT8) is a recently identified major autoantigen in type 1 diabetes, and autoantibodies to ZnT8 (ZnT8A) are new markers for disease prediction and diagnosis. Here we report the results of the first international proficiency evaluation of ZnT8A assays by the Diabetes Antibody Standardization Program (DASP). METHODS: After a pilot workshop in 2007, an expanded ZnT8A workshop was held in 2009, with 26 participating laboratories from 13 countries submitting results of 63 different assays. ZnT8A levels were measured in coded sera from 50 patients with newly diagnosed type 1 diabetes and 100 blood donor controls. Results were analyzed comparing area under the ROC curve (ROC-AUC), sensitivity adjusted to 95% specificity (AS95), concordance of sample ZnT8A positive or negative designation, and autoantibody levels. RESULTS: ZnT8A radio binding assays (RBAs) based on combined immunoprecipitation of the 2 most frequent ZnT8 COOH-terminal domain polymorphic variants showed a median ROC-AUC of 0.848 [interquartile range (IQR) 0.796–0.878] and a median AS95 of 70% (IQR 60%–72%). These RBAs were more sensitive than assays using as antigen either 1 ZnT8 variant only or chimeric constructs joining NH2- and COOH-terminal domains, assays based on immunoprecipitation and bioluminescent detection, or assays based on immunofluorescent staining of cells transfected with full-length antigen. CONCLUSIONS: The DASP workshop identified immunoprecipitation-based ZnT8A assays and antigen constructs that achieved both a high degree of sensitivity and specificity and were suitable for more widespread clinical application.
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Zinc Transporter 8 autoantibodies increase the predictive value of islet autoantibodies for function loss of technically successful solitary pancreas transplant.
Transplantation, 2011Co-Authors: Margherita Occhipinti, Vito Lampasona, Fabio Vistoli, Elena Bazzigaluppi, Marina Scavini, Ugo Boggi, Piero Marchetti, Emanuele BosiAbstract:BACKGROUND Despite the success rate of solitary pancreas transplantation in type 1 diabetes with preserved kidney function has greatly improved in recent years, a residual proportion of failures persists. METHODS With the aim of investigating autoimmunity as an unrecognized cause of graft failure, we measured autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A) and the recently discovered Zinc Transporter 8 antigen (ZnT8A) in 25 recipients of technically successful solitary pancreas transplantation. RESULTS The overall pancreas graft survival was 92%, 88%, and 80% at 2, 4, and 6 years, respectively. Fourteen patients (56%) had one or more autoantibodies before transplantation, with no effect on subsequent pancreas graft outcome. After transplantation, major autoantibody changes (serum conversion from negative to positive, spreading from one to multiple autoantibodies, or titer increase) were observed in 5 of 25 recipients: in four patients, the autoantibody change was followed by the loss of graft function (95% sensitivity, 80% positive predictive value), with a significantly lower graft survival compared with patients without autoantibodies (P
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Zinc Transporter 8 autoantibodies increase the predictive value of islet autoantibodies for function loss of technically successful solitary pancreas transplant
Transplantation, 2011Co-Authors: Margherita Occhipinti, Vito Lampasona, Fabio Vistoli, Elena Bazzigaluppi, Marina Scavini, Ugo Boggi, Piero Marchetti, Emanuele BosiAbstract:BACKGROUND Despite the success rate of solitary pancreas transplantation in type 1 diabetes with preserved kidney function has greatly improved in recent years, a residual proportion of failures persists. METHODS With the aim of investigating autoimmunity as an unrecognized cause of graft failure, we measured autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A) and the recently discovered Zinc Transporter 8 antigen (ZnT8A) in 25 recipients of technically successful solitary pancreas transplantation. RESULTS The overall pancreas graft survival was 92%, 88%, and 80% at 2, 4, and 6 years, respectively. Fourteen patients (56%) had one or more autoantibodies before transplantation, with no effect on subsequent pancreas graft outcome. After transplantation, major autoantibody changes (serum conversion from negative to positive, spreading from one to multiple autoantibodies, or titer increase) were observed in 5 of 25 recipients: in four patients, the autoantibody change was followed by the loss of graft function (95% sensitivity, 80% positive predictive value), with a significantly lower graft survival compared with patients without autoantibodies (P<0.0001). The addition of ZnT8A to GADA and IA-2A increased the number of identified autoantibody changes from three to five of 25 recipients and the number of predicted graft function loss from two to four out of five graft losses. CONCLUSIONS Detection of major autoantibody changes after technically successful solitary pancreas transplantation is predictive of subsequent loss of graft function. ZnT8A in addition to GADA and IA-2A are a useful marker to be included in the screening panel of posttransplant immune monitoring.
Margherita Occhipinti - One of the best experts on this subject based on the ideXlab platform.
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Zinc Transporter 8 autoantibodies increase the predictive value of islet autoantibodies for function loss of technically successful solitary pancreas transplant.
Transplantation, 2011Co-Authors: Margherita Occhipinti, Vito Lampasona, Fabio Vistoli, Elena Bazzigaluppi, Marina Scavini, Ugo Boggi, Piero Marchetti, Emanuele BosiAbstract:BACKGROUND Despite the success rate of solitary pancreas transplantation in type 1 diabetes with preserved kidney function has greatly improved in recent years, a residual proportion of failures persists. METHODS With the aim of investigating autoimmunity as an unrecognized cause of graft failure, we measured autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A) and the recently discovered Zinc Transporter 8 antigen (ZnT8A) in 25 recipients of technically successful solitary pancreas transplantation. RESULTS The overall pancreas graft survival was 92%, 88%, and 80% at 2, 4, and 6 years, respectively. Fourteen patients (56%) had one or more autoantibodies before transplantation, with no effect on subsequent pancreas graft outcome. After transplantation, major autoantibody changes (serum conversion from negative to positive, spreading from one to multiple autoantibodies, or titer increase) were observed in 5 of 25 recipients: in four patients, the autoantibody change was followed by the loss of graft function (95% sensitivity, 80% positive predictive value), with a significantly lower graft survival compared with patients without autoantibodies (P
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Zinc Transporter 8 autoantibodies increase the predictive value of islet autoantibodies for function loss of technically successful solitary pancreas transplant
Transplantation, 2011Co-Authors: Margherita Occhipinti, Vito Lampasona, Fabio Vistoli, Elena Bazzigaluppi, Marina Scavini, Ugo Boggi, Piero Marchetti, Emanuele BosiAbstract:BACKGROUND Despite the success rate of solitary pancreas transplantation in type 1 diabetes with preserved kidney function has greatly improved in recent years, a residual proportion of failures persists. METHODS With the aim of investigating autoimmunity as an unrecognized cause of graft failure, we measured autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A) and the recently discovered Zinc Transporter 8 antigen (ZnT8A) in 25 recipients of technically successful solitary pancreas transplantation. RESULTS The overall pancreas graft survival was 92%, 88%, and 80% at 2, 4, and 6 years, respectively. Fourteen patients (56%) had one or more autoantibodies before transplantation, with no effect on subsequent pancreas graft outcome. After transplantation, major autoantibody changes (serum conversion from negative to positive, spreading from one to multiple autoantibodies, or titer increase) were observed in 5 of 25 recipients: in four patients, the autoantibody change was followed by the loss of graft function (95% sensitivity, 80% positive predictive value), with a significantly lower graft survival compared with patients without autoantibodies (P<0.0001). The addition of ZnT8A to GADA and IA-2A increased the number of identified autoantibody changes from three to five of 25 recipients and the number of predicted graft function loss from two to four out of five graft losses. CONCLUSIONS Detection of major autoantibody changes after technically successful solitary pancreas transplantation is predictive of subsequent loss of graft function. ZnT8A in addition to GADA and IA-2A are a useful marker to be included in the screening panel of posttransplant immune monitoring.
Janet M Wenzlau - One of the best experts on this subject based on the ideXlab platform.
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Changes in Zinc Transporter 8 Autoantibodies Following Type 1 Diabetes Onset: The Type 1 Diabetes Genetics Consortium Autoantibody Workshop
Diabetes Care, 2015Co-Authors: Janet M Wenzlau, Lisa M. Frisch, John C Hutton, Pamela R. Fain, Howard W DavidsonAbstract:Zinc Transporter 8 autoantibodies (ZnT8A) were analyzed in sera from 1,504 subjects as part of the Type 1 Diabetes Genetics Consortium (T1DGC) Autoantibody Workshop. For these participants with type 1 diabetes (T1D), samples were collected within 3 years of T1D diagnosis. ZnT8A were detected in 862 subjects (57.3%), with the highest frequencies and median titers being associated with the shortest duration of disease. ZnT8A were present at similar frequencies in non-Hispanic whites, non-Hispanic blacks, and Hispanics, but significantly less prevalent in those of Asian ancestry. Sera containing ZnT8A selectively recognizing at least one of the SLC30A8 single nucleotide polymorphisms (encoding ZnT8A) were detected in all populations; however, Trp-specific sera were much less frequent in non-Hispanic blacks, consistent with the anticipated lower frequency of the SLC30A8 rs13266634 T allele in African American populations. ZnT8A positivity was associated with HLA-DQ8, but this was primarily due to the DRB1*0404-DQ8 haplotype. This was in contrast to autoantibodies to IA-2 that were strongly associated with DRB1*0401-DQ8. These effects appeared essentially independent of racial or ethnic background. The DRB1*0401-DQ8 and DRB1*0404-DQ8 haplotypes were associated with T1D subjects positive for GAD65, IA-2, and ZnT8A. In contrast to DRB1*0401-DQ8, there was no significant association of DRB1*0404-DQ8 with single or dual autoantibody positivity. The DRB1*0404-DQ8 haplotype was also associated with T1D subjects whose sera recognized both polymorphic variants of Zinc Transporter 8, an effect not seen for DRB1*0401-DQ8.
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Zinc Transporter 8 (ZnT8) and β cell function.
Trends in endocrinology and metabolism: TEM, 2014Co-Authors: Howard W Davidson, Janet M Wenzlau, Richard M. O'brienAbstract:Human pancreatic β cells have exceptionally high Zinc content. In β cells the highest Zinc concentration is in insulin secretory granules, from which it is cosecreted with the hormone. Uptake of Zinc into secretory granules is mainly mediated by Zinc Transporter 8 (ZnT8), the product of the SLC30A8 [solute carrier family 30 (Zinc Transporter), member 8] gene. The minor alleles of several single-nucleotide polymorphisms (SNPs) in SLC30A8 are associated with decreased risk of type 2 diabetes (T2D), but the precise mechanisms underlying the protective effects remain uncertain. In this article we review current knowledge of the role of ZnT8 in maintaining Zinc homeostasis in β cells, its role in glucose metabolism based on knockout mouse studies, and current theories regarding the link between ZnT8 function and T2D.
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No relation between cystic fibrosis-related diabetes and type 1 diabetes autoimmunity.
Diabetes care, 2012Co-Authors: Peter A. Gottlieb, Janet M Wenzlau, Sunanda R. Babu, Melena D. Bellin, Brigitte I. Frohnert, Antoinette MoranAbstract:Diabetes is the most common comorbidity in individuals with cystic fibrosis. The etiology is poorly understood. Data on the presence of diabetes autoantibodies are conflicting, and little is known about type 1 diabetes gene associations. Our goal was to determine the prevalence of antibodies and HLA haplotypes known to be associated with type 1 diabetes in cystic fibrosis–related diabetes (CFRD). Patients with CFRD with fasting hyperglycemia were recruited from the University of Minnesota. Serum for antibodies and buffy coats for HLA were sent for analysis to the Barbara Davis Center for Childhood Diabetes (BDC). All patients gave informed consent. The Eisenbarth laboratory at BDC serves as the autoantibody/HLA reference laboratory for large national diabetes studies. Insulin, insulinoma-associated protein 2 (IA-2), GAD65, and Zinc Transporter 8 (ZnT8) autoantibodies were measured by radioimmunoassay …
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Genetic association of Zinc Transporter 8 (ZnT8) autoantibodies in type 1 diabetes cases
Diabetologia, 2012Co-Authors: Joanna M. M. Howson, Janet M Wenzlau, John C Hutton, Ezio Bonifacio, S Krause, Helen E. Stevens, Deborah J. Smyth, Ag Ziegler, John A. Todd, Peter AchenbachAbstract:Aims/hypothesis Autoantibodies to Zinc Transporter 8 (ZnT8A) are associated with risk of type 1 diabetes. Apart from the SLC30A8 gene itself, little is known about the genetic basis of ZnT8A. We hypothesise that other loci in addition to SLC30A8 are associated with ZnT8A.
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Zinc Transporter-8 autoantibodies improve prediction of type 1 diabetes in relatives positive for the standard biochemical autoantibodies.
Diabetes care, 2012Co-Authors: David Boulware, Janet M Wenzlau, John C Hutton, Polly J. Bingley, Craig A. Beam, Carla J. Greenbaum, Jeffrey P. Krischer, Jay M. Sosenko, Jay S. SkylerAbstract:OBJECTIVE We assessed diabetes risk associated with Zinc Transporter-8 antibodies (ZnT8A), islet cell antibodies (ICA), and HLA type and age in relatives of people with type 1 diabetes with the standard biochemical autoantibodies (BAA) to insulin (IAA), GAD65 (GAD65A), and/or insulinoma-associated protein 2 antigen (IA-2A). RESEARCH DESIGN AND METHODS For this analysis, 2,256 relatives positive for at least one BAA, of whom 142 developed diabetes, were tested for ZnT8A, ICA, and HLA genotype followed by biannual oral glucose tolerance tests. ZnT8A were also tested in 911 randomly chosen antibody-negative relatives. RESULTS ZnT8A were associated with the other BAA (548 of 2,256 [24.3%] BAA + vs. 8 of 911 [0.8%] BAA − , P P + relatives with ZnT8A than ZnT8A − relatives (31 vs. 7%, P P = 0.03), IA-2A (2.15, P = 0.005), IAA (1.73, P = 0.01), ICA (2.37, P = 0.002), and ZnT8A (1.87, P = 0.03) independently predicted diabetes, whereas HLA type (high and moderate vs. low risk) and GAD65A did not ( P = 0.81 and 0.86, respectively). CONCLUSIONS In relatives with one standard BAA, ZnT8A identified a subset at higher diabetes risk. ZnT8A predicted diabetes independently of ICA, the standard BAA, age, and HLA type. ZnT8A should be included in type 1 diabetes prediction and prevention studies.
Zhiguang Zhou - One of the best experts on this subject based on the ideXlab platform.
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Different role of Zinc Transporter 8 between type 1 diabetes mellitus and type 2 diabetes mellitus
Journal of Diabetes Investigation, 2016Co-Authors: Bo Yi, Gan Huang, Zhiguang ZhouAbstract:Diabetes can be simply classified into type 1 diabetes mellitus and type 2 diabetes mellitus. Zinc Transporter 8 (ZnT8), a novel islet autoantigen, is specifically expressed in insulin-containing secretory granules of β-cells. Genetic studies show that the genotypes of SLC30A8 can determine either protective or diabetogenic response depending on environmental and lifestyle factors. The ZnT8 protein expression, as well as Zinc content in β-cells, was decreased in diabetic mice. Thus, ZnT8 might participate in insulin biosynthesis and release, and subsequently involved deteriorated β-cell function through direct or indirect mechanisms in type 1 diabetes mellitus and type 2 diabetes mellitus. From a clinical feature standpoint, the prevalence of ZnT8A is gradiently increased in type 2 diabetes mellitus, latent autoimmune diabetes in adults and type 1 diabetes mellitus. The frequency and epitopes of ZnT8-specific T cells and cytokine release by ZnT8-specific T cells are also different in diabetic patients and healthy controls. Additionally, the response to ZnT8 administration is also different in type 1 diabetes mellitus and type 2 diabetes mellitus. In the present review, we summarize the literature about clinical aspects of ZnT8 in the pathogenesis of diabetes, and suggest that ZnT8 might play a different role between type 1 diabetes mellitus and type 2 diabetes mellitus.
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Current and Future Clinical Applications of Zinc Transporter-8 in Type 1 Diabetes Mellitus
Chinese medical journal, 2015Co-Authors: Gan Huang, Zhiguang ZhouAbstract:Objective: To evaluate the utility of Zinc Transporter-8 (ZnT8) in the improvement of type 1 diabetes mellitus (T1DM) diagnosis and prediction, and to explore whether ZnT8 is a potential therapeutic target in T1DM. Data Sources: A search was conducted within the medical database PubMed for relevant articles published from 2001 to 2015. The search terms are as follows: "ZnT8," "type 1 diabetes," "latent autoimmune diabetes in adults," "type 2 diabetes," "islet autoantibodies," "Zinc supplement," "T cells," "β cell," "immune therapy." We also searched the reference lists of selected articles. Study Selection: English-language original articles and critical reviews concerning ZnT8 and the clinical applications of islet autoantibodies in diabetes were reviewed. Results: The basic function of ZnT8 is maintaining intracellular Zinc homeostasis, which modulates the process of insulin biosynthesis, storage, and secretion. Autoantibodies against ZnT8 (ZnT8A) and ZnT8-specific T cells are the reliable biomarkers for the identification, stratification, and characterization of T1DM. Additionally, the results from the animal models and clinical trials have shown that ZnT8 is a diabetogenic antigen, suggesting the possibility of ZnT8-specific immunotherapy as an alternative for T1DM therapy. Conclusions: ZnT8 is a novel islet autoantigen with a widely potential for clinical applications in T1DM. However, before the large-scale clinical applications, there are still many problems to be solved.
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Zinc Transporter 8 autoantibody znt8a could help differentiate latent autoimmune diabetes in adults lada from phenotypic type 2 diabetes mellitus
Diabetes-metabolism Research and Reviews, 2013Co-Authors: Gan Huang, Shuoming Luo, Yufei Xiang, Lingling Pan, Zhiguang ZhouAbstract:Background The ZnT8A is an independent marker for diagnosis of type 1 diabetes mellitus. We investigated the distribution and clinical features of ZnT8A positive latent autoimmune diabetes in adult (LADA) patients to explore the potential diagnostic application. Methods A total of 3062 phenotypic T2DM patients were randomly selected from a national multicenter study – the LADA China Study. Radioligand binding assays were applied to detect the presence of ZnT8A, GADA and IA-2A. HbA1c, fasting C-peptide and serum lipid levels were followed up with ZnT8A positive patients. Results The positive prevalence of ZnT8A, GADA and IA-2A in phenotypic T2DM patients was 1.99%(61/3062), 6.43% (197/3062) and 1.96% (60/3062), respectively. The ZnT8A positivity was lower than that of GADA(x2 = 74.8, p 0.05). The positivity of ZnT8A in IA-2A positive patients was higher than that in GADA positive patients(38.3% vs. 10.7%, x2 = 24.8, p < 0.001). On the basis of GADA and IA-2A positivity, the ZnT8A assay enhanced the diagnostic prevalence of LADA from 7.58 to 8.62%. The LADA patients who were positive for ZnT8A had higher systolic blood pressure when compared with GADA positive cases(p = 0.049) and higher total cholesterol levels when compared with antibody-negative T2DM patients(p = 0.035). Conclusion The detection of ZnT8A at the basis of GADA and IA-2A can improve diagnostic sensitivity of Chinese LADA. Copyright © 2013 John Wiley & Sons, Ltd.
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Value of Zinc Transporter 8 autoantibody in the diagnostic classification of acute-onset diabetics
Zhonghua yi xue za zhi, 2010Co-Authors: Lin Yang, Howard W Davidson, Janet M Wenzlau, John C Hutton, Gan Huang, Shuoming Luo, Jian Peng, Xiang Yan, Zhiguang ZhouAbstract:Objective To explore the application significance of Zinc Transporter 8 autoantibody (ZnT8A) in the diagnostic classification of acute-onset diabetics. Methods According to the status of glutamic acid decarboxylase antibody(GADA) and tyrosine phosphatase antibody( IA2-A), 453 acute-onset diabetics were divided into A + subgroup ( any antibody positive ) and A - subgroup ( both antibodies negative). A total of 555 type 2 diabetics and 405 healthy controls were recruited. The distribution and correlated factors of ZnT8A were analyzed in the acute-onset diabetic group and two subgroups( A + and A- ). The clinical characteristics were compared between the patients with ZnT8A positive alone and patients without any antibody. All these islet antibodies were measured by radioligand assay. Results The prevalence of ZnT8A in acute-onset diabetics was 24.3% and it was significantly higher than that in type 2 diabetics( 1.8% ) and healthy controls( 1.0% ) ( both P ＜0.01 ). The frequency of ZnT8A in A + subgroup was much higher than A - subgroup(29.7% vs 15.8%, P ＜ 0.01 ). The positive rates of ZnT8A were much higher in all the subgroups with age at onset of ＜30yr than those with ≥30yr(0 -9, 34.9%; 10 -19, 26.7%; 20 -29, 26.3% vs ≥30 yr, 18.3%; all P＜0.05); furthermore, the rates were also higher in BMI ＜21.0 kg/m2 and 21.0 -25.0 kg/m2 subgroups than in BMI ＞25.0 kg/m2 subgroup(25.5% and 25.9% vs 8.7%, both P ＜ 0.05 ). The ZnT8A level was only positively correlated with IA2-A titer( r =0.165, P=0.01), but not related to such factors as GADA titer, age at onset, duration, body mass index,HbAlc and CP levels( all P ＞0.05). As compared with Ab- patients, the patients with ZnT8A positive alone had much higher insulin injection dosage [( 35.5 ± 9.3 ) U/d vs ( 29.8 ± 14.7 ) U/d, P ＜ 0.05], and much lower systolic blood pressures [( 107 ± 15 ) mm Hg vs ( 113 ± 16 ) mm Hg, P ＜ 0.05] and diastolic blood pressures [(69 ± 12) mm Hg vs (73 ± 12) mm Hg, P ＜ 0.05]. Conclusion ZnT8A testing may be applied in the diagnostic classification of acute-onset diabetics, especially in those without an evidence of GADA and IA2-A since it helps to identify a clinical phenotype which is more similar to the classic type 1 diabetes. Key words: Diabetes mellitus,type 1; Diagnosis; ZnT8 autoantibody; Acute-onset
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Zinc Transporter 8 and its autoantibody
2009Co-Authors: Shuoming Luo, Gan Huang, Zhiguang ZhouAbstract:Zinc is an important component in the process of insulin synthesis, storage and secretion. Therefore beta cells need very efficient and special Transporters to accumulate sufficient amounts of Zinc in se-cretion vesicles. Recent studies suggest the Zinc Transporter eight (ZnT8) is a major autoantigen in type 1 di-abetes. It is a pancreatic beta-cell-specific Zinc Transporter,and plays an important role in the synthesis and secretion of insulin by affecting the concentration of Zinc. ZnT8 autoantibodies are important for diagnosis and prediction in autoimmune diabetes, especially in subjects whose common autoantibodies are negative. The sin-gle nucleotide polymorphism of ZnT8 gene(SLC30A8)determines ZnT8 autoantibodies specificity. Key words: Zinc Transporter eight; Autoantibody; Beta cell; Zinc; Type 1 diabetes mellitus
