The dynamic changes of zinc transporter 8 autoantibodies in Czech children from the onset of Type 1 diabetes mellitus

Petruželková, Lenka; Ananieva-Jordanova, Rossitza; Včeláková, Jana; Veselý, Zdeněk; Stechova, Katerina; Lebl, Jan; Dušátková, Petra; Šumnı́k, Zdenĕk; Coles, Rebecca; Powell, Michael J.; Furmaniak, Jadwiga; Smith, Bernard Rees; Koloušková, Stanislava

doi:10.1111/dme.12308

Cited by 33 publications

(42 citation statements)

References 27 publications

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“…Beta‐cell destruction in T1DM is immune‐mediated; thus, measurement of autoantibodies levels provides information relevant for the disease diagnosis and monitoring. In agreement with previous observations, we noted that levels of all autoantibodies decreased linearly in T1DM patients during follow‐up …”

Section: Discussionsupporting

confidence: 93%

“…In agreement with previous observations, we noted that levels of all autoantibodies decreased linearly in T1DM patients during follow-up. 28,29 A gradual decline in pancreatic beta-cell function and mass in T1DM results in insufficient insulin production with consequent hyperglycemia. 1 As the rate of decline in insulin secretion varies significantly between individuals, 15 insight into changes in beta-cell mass and ongoing insulitis in living subjects with T1DM would be highly desirable.…”

Section: Discussionmentioning

confidence: 99%

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Temporal dynamics of serum let‐7g expression mirror the decline of residual beta‐cell function in longitudinal observation of children with type 1 diabetes

et al. 2018

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Background/Objective In type 1 diabetes mellitus (T1DM), the introduction of insulin is typically followed by a brief remission period, with subsequent gradual decline in beta‐cell function. Several studies described altered profile of circulating miRNAs (microRNAs) in T1DM patients and proposed them as biomarkers of associated pathologic processes. Hypothesis Serum miRNA expression profile reflects residual beta‐cell function and autoimmunity in T1DM. Subjects The profiling group included patients with: GCK‐MODY (N = 13), T1DM (N = 9), and 10 healthy controls. The longitudinal group included 34 patients with samples collected at diagnosis of T1DM and first, third, and fourth to eighth year since diagnosis. Methods We reanalyzed data from the profiling group for miRNAs differentially expressed between patients with T1DM, other types of diabetes and controls. Afterward, we shortlisted miRNAs on the basis of this reanalysis and literature review and quantified their expression with quantitative polymerase chain reaction. Additionally, we measured the levels of anti‐islet antibodies (islet cell antibodies, glutamic acid decarboxylase antibodies, IA2 antibodies, and ZnT8A) and C‐peptide concentrations across the four timepoints in the longitudinal group. Results miR‐24 and let‐7g serum expression differed significantly between GCK‐MODY, controls, and HbA1c‐matched T1DM patients; P < 0.05, false discovery rate < 0.05. Autoantibodies levels showed decreasing linear trend in repeated timepoints (all P < 0.0001). C‐peptide concentration peaked during the first year after diagnosis, corresponding to remission phase, and declined in consecutive measurements. This dynamic was evidenced for let‐7g expression levels (P = 0.0058). Conclusions The pattern of let‐7g expression change during the course of diabetes mirrors that of C‐peptide levels, hinting at this microRNA's association with the residual mass of the beta cells in patients with T1DM.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Temporal dynamics of serum let‐7g expression mirror the decline of residual beta‐cell function in longitudinal observation of children with type 1 diabetes

et al. 2018

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“…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]. Interestingly, in Chinese T1D subject ZnT8 Ab and IA-2 Ab were less prevalent than in Caucasian populations, but similar to Japanese [27].…”

Section: Discussionsupporting

confidence: 90%

“…A somewhat lower prevalence for GAD Ab and ZnT8 Ab in children without diabetes has been reported previously [18,20].…”

Section: Discussionmentioning

confidence: 61%

“…IA-2 Ab levels > 125 WHO units/mL were considered positive in this assay as recommended in the kit instructions. Ab to ZnT8 were measured by ELISA [18] using kits from RSR Ltd. and values of ZnT8 Ab of ≥ 15 units/mL were considered positive, following the manufacturer's recommendations. In (IASP, 2013), the GAD Ab ELISA showed 78% sensitivity and 98% specificity, IA-2 Ab IPA 66% sensitivity and 98% specificity and ZnT8 Ab ELISA 74% sensitivity and 99% specificity.…”

Section: Ab Assaysmentioning

confidence: 99%

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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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Changes in innate and adaptive immunity over the first year after the onset of type 1 diabetes

et al. 2019

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The dynamic changes of zinc transporter 8 autoantibodies in Czech children from the onset of Type 1 diabetes mellitus

Cited by 33 publications

References 27 publications

Temporal dynamics of serum let‐7g expression mirror the decline of residual beta‐cell function in longitudinal observation of children with type 1 diabetes

Temporal dynamics of serum let‐7g expression mirror the decline of residual beta‐cell function in longitudinal observation of children with type 1 diabetes

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

Changes in innate and adaptive immunity over the first year after the onset of type 1 diabetes

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