Autoantibodies against zinc transporter 8 are related to age, metabolic state and HLA DR genotype in children with newly diagnosed type 1 diabetes

Salonen, Kirsi M.; Ryhänen, Samppa J.; Härkönen, Taina; Ilonen, Jorma; Knip, Mikael

doi:10.1002/dmrr.2440

Cited by 57 publications

(55 citation statements)

References 25 publications

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“…The prevalence of ZnT8 Ab was decreased in DR3/DR4 heterozygotes when compared with those with other DR combinations (p < 0.001). Subjects with the neutral DR13-DQB1*0604 haplotype tested more frequently positive for ZnT8 Ab than the rest of the population (p < 0.001) [26]. The frequency of ZnT8 Ab may be related to some HLA differences, and be similar in similar populations, as in the study of Polish neighbours, Czech T1DM children, the prevalence of this Ab was similar to our results [18].…”

Section: Discussionsupporting

confidence: 89%

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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Section: Discussionsupporting

confidence: 89%

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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“…These data confirm that there is no a priori reason to expect that the expression of high-risk alleles alone will result in increased autoreactivity to ZnT8 [37]. The mechanisms behind the disease progression from autoimmunity to T1DM and the role of HLA class alleles remain hypothetical [35]. …”

Section: Discussionsupporting

confidence: 59%

“…Although surprisingly, there was an association between IA-2 autoantibody positivity and the T1DM-protective allele HLA-DQB1*03:01. In T1DM, ZnT8 was also associated with the HLA genotype [35]; all ZnT8 variants were positively associated with either DQ6.4 (DQBI*06:04) or DQ8 (DQB1*03:02) but dominantly negatively associated with DQ2 (DQB1*02:01/02:02) [25]. A correlation between ZnT8 positivity and HLA-DQB1*03:02 genotypes has also been reported [36].…”

Section: Discussionmentioning

confidence: 99%

Anti-Zinc Transporter Protein 8 Antibody Testing Is Not Informative in Routine Prediabetes Screening in Young Patients with Autoimmune Thyroiditis and Celiac Disease

et al. 2016

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Background/Aims: Patients with type 1 diabetes mellitus (T1DM), autoimmune thyroiditis (ATD), and celiac disease (CD) are at increased risk for developing other autoimmune diseases. We evaluated zinc transporter 8 (ZnT8) prevalence in patients with ATD and/or CD in order to define the usefulness of ZnT8 autoantibodies for prediabetes screening. Methods: Eighty-one young patients with ATD and/or CD were included in the study; 32 subjects with clinical onset of T1DM were enrolled as a control group. GAD65, IA-2, and ZnT8 antibodies were measured. An intravenous glucose tolerance test, C-peptide, glycosylated hemoglobin levels, and genomic analysis of HLA-DQA1* and -DQB1* were also considered in patients positive for autoantibodies. Results: The ZnT8 prevalence was higher in T1DM patients than in patients with other autoimmune diseases (p < 0.001); positive ZnT8 detection was found in 2 ATD (p = 0.004) and 3 ATD + CD (p = 0.04) patients. Positive ZnT8 was associated with GAD65 (p = 0.01) but not with IA-2 positivity. No correlation between ZnT8 detection and the number of T1DM-susceptible HLA-DQ heterodimers was found. Pathological C-peptide levels and insulin response were found in subjects with islet autoimmunity and genetic susceptibility. Conclusion: ZnT8 autoantibodies detection in ATD and/or CD patients is low, and routine ZnT8 screening is not justified. ZnT8 evaluation may be recommended in subjects with autoimmune diseases as a marker for predicting compromised insulin secretion.

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“…Serum ZnT8A levels were analyzed by a radiobinding assay as described earlier (4,5). Islet cell antibody (ICA) was detected with indirect immunofluorescence, whereas GAD antibody (GADA), IA-2A, and insulin autoantibody (IAA) were quantified with specific radiobinding assays (6).…”

Section: Methodsmentioning

confidence: 99%

Positivity for Zinc Transporter 8 Autoantibodies at Diagnosis Is Subsequently Associated With Reduced β-Cell Function and Higher Exogenous Insulin Requirement in Children and Adolescents With Type 1 Diabetes

et al. 2015

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OBJECTIVEThis study assessed the relationship between autoantibodies against zinc transporter 8 (ZnT8A) and disease characteristics at diagnosis of type 1 diabetes and during the first 2 years.RESEARCH DESIGN AND METHODSChildren, younger than 15 years of age (n = 723) who were newly diagnosed with diabetes, were analyzed for ZnT8A, other diabetes-associated autoantibodies, HLA DR-DQ alleles, and metabolic status, which was monitored by pH, plasma glucose, and occurrence of ketoacidosis at diagnosis and through follow-up of C-peptide concentrations, exogenous insulin dose, and glycosylated hemoglobin for 2 years after the diagnosis.RESULTSZnT8A positivity was detected in 530 children (73%). Positivity for ZnT8A was associated with older age (median 8.9 vs. 8.2 years, P = 0.002) and more frequent ketoacidosis (24% vs. 15%, P = 0.013). Children carrying the HLA DR3 allele were less often ZnT8A positive (66% vs. 77%, P = 0.002) than others. ZnT8A-positive children had lower serum C-peptide concentrations (P = 0.008) and higher insulin doses (P = 0.012) over time than their ZnT8A-negative peers.CONCLUSIONSPositivity for ZnT8A at diagnosis seems to reflect a more aggressive disease process before and after diagnosis.

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Autoantibodies against zinc transporter 8 are related to age, metabolic state and HLA DR genotype in children with newly diagnosed type 1 diabetes

Abstract: Antibodies for ZnT8 is related to age and metabolic status at diagnosis as well as HLA genotype but does not significantly improve the detection rate of β-cell autoimmunity in Finnish children and adolescents affected by T1D.

Cited by 57 publications

References 25 publications

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

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

Anti-Zinc Transporter Protein 8 Antibody Testing Is Not Informative in Routine Prediabetes Screening in Young Patients with Autoimmune Thyroiditis and Celiac Disease

Positivity for Zinc Transporter 8 Autoantibodies at Diagnosis Is Subsequently Associated With Reduced β-Cell Function and Higher Exogenous Insulin Requirement in Children and Adolescents With Type 1 Diabetes

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