Extremely Early Appearance of Islet Autoantibodies in Genetically Susceptible Children

IF 3.9 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Pediatric Diabetes Pub Date : 2023-12-11 DOI:10.1155/2023/9973135

Anni Kyrönniemi, Toni Valtanen, J. Koskenniemi, P. Vähäsalo, T. Härkönen, J. Ilonen, J. Toppari, Mikael Knip, R. Veijola

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引用次数: 0

Abstract

Objective. We studied the characteristics of children who developed islet autoantibodies by the age of 0.50 years and hypothesized that the appearance of extremely early islet autoimmunity differs between four birth cohorts within 1994–2019 according to the change in the incidence of Type 1 diabetes (T1D) in Finland. Methods. Data from Finnish children participating in the Type 1 Diabetes Prediction and Prevention (DIPP) study, or the Environmental Determinants of Diabetes in the Young (TEDDY) study were analyzed. These studies follow children with increased HLA-conferred risk for T1D with regular measurements of islet autoantibodies. Maternally transferred antibodies were excluded by comparing islet autoantibodies in cord serum, child’s first follow-up serum and the maternal serum. Results. Among 20,979 Finnish children at increased risk to T1D, 53 (0.25%) developed at least one islet autoantibody at the age of ≤0.50 years. During a mean follow-up of 8.1 years, 15.1% progressed to T1D (median age at diagnosis 2.0 years), 43.4% developed confirmed islet autoimmunity but no T1D, and 41.5% had only transient islet autoantibodies. IAA was the most common first-appearing autoantibody. Among progressors, age at diagnosis was 1.0–2.4 years in children with IAA-initiated autoimmunity and 4.5–16.1 years in ZnT8A-initiated autoimmunity. When comparing children developing autoantibodies either at the age of ≤0.50 years or 0.51–0.75 years, confirmed positivity during follow-up was more common in the older group (81.7% vs. 58.5%; p = 0.002 ). In four birth cohorts within 1994–2019 appearance of islet autoantibodies at the age of ≤0.50 years decreased towards the most recent birth cohorts ( p = 0.016 ). Conclusion. Islet autoimmunity by the age of 0.50 years was rare in genetically susceptible children and was typically initiated with IAA. Confirmed positivity was less common in children with autoantibodies at age ≤0.50 than at slightly older age. The secular decrease of islet autoimmunity before age 0.50 years was observed. This trial is registered with NCT03269084 and NCT00279318.

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遗传易感儿童极早出现胰岛自身抗体

目的。我们研究了 0.50 岁前出现胰岛自身抗体的儿童的特征，并假设根据芬兰 1 型糖尿病（T1D）发病率的变化，1994-2019 年间四个出生队列中出现极早期胰岛自身免疫的情况有所不同。研究方法分析了参与1型糖尿病预测与预防（DIPP）研究或青少年糖尿病环境决定因素（TEDDY）研究的芬兰儿童的数据。这些研究通过定期测量胰岛自身抗体，对 HLA 遗传风险增加的 1 型糖尿病患儿进行跟踪调查。通过比较脐带血清、儿童首次随访血清和母体血清中的胰岛自身抗体，排除了母体转移的抗体。研究结果在20979名T1D高危芬兰儿童中，有53人（0.25%）在≤0.50岁时出现至少一种胰岛自身抗体。在平均8.1年的随访期间，15.1%的患儿发展为T1D（诊断年龄中位数为2.0岁），43.4%的患儿确诊为胰岛自身免疫，但未发展为T1D，41.5%的患儿只有短暂的胰岛自身抗体。IAA是最常见的首次出现的自身抗体。在进展期患儿中，IAA引发自身免疫的患儿确诊年龄为1.0-2.4岁，ZnT8A引发自身免疫的患儿确诊年龄为4.5-16.1岁。如果比较在≤0.50岁或0.51-0.75岁时出现自身抗体的儿童，随访期间证实阳性的儿童在年龄较大的组别中更为常见（81.7%对58.5%；P = 0.002）。在1994-2019年期间的四个出生队列中，年龄≤0.50岁时出现胰岛自身抗体的人数在最近的出生队列中有所减少（p = 0.016）。结论0.50岁前出现胰岛自身免疫的情况在遗传易感儿童中很少见，通常是由IAA开始的。与年龄稍大的儿童相比，≤0.50岁时自身抗体阳性的儿童更少。据观察，胰岛自身免疫在0.50岁之前会逐渐下降。该试验已在 NCT03269084 和 NCT00279318 上注册。

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来源期刊

Pediatric Diabetes 医学-内分泌学与代谢

CiteScore

6.60

自引率

14.70%

发文量

141

审稿时长

4-8 weeks

期刊介绍： Pediatric Diabetes is a bi-monthly journal devoted to disseminating new knowledge relating to the epidemiology, etiology, pathogenesis, management, complications and prevention of diabetes in childhood and adolescence. The aim of the journal is to become the leading vehicle for international dissemination of research and practice relating to diabetes in youth. Papers are considered for publication based on the rigor of scientific approach, novelty, and importance for understanding mechanisms involved in the epidemiology and etiology of this disease, especially its molecular, biochemical and physiological aspects. Work relating to the clinical presentation, course, management and outcome of diabetes, including its physical and emotional sequelae, is considered. In vitro studies using animal or human tissues, whole animal and clinical studies in humans are also considered. The journal reviews full-length papers, preliminary communications with important new information, clinical reports, and reviews of major topics. Invited editorials, commentaries, and perspectives are a regular feature. The editors, based in the USA, Europe, and Australasia, maintain regular communications to assure rapid turnaround time of submitted manuscripts.