Zinc transporter 8 autoantibodies in patients with type 1 diabetes from a multiethnic population and their first degree relatives.

Débora Batista Araujo, Hanna Skärstrand, Bianca Barone, Joana Rodrigues Dantas, Rosane Kupfer, Lenita Zajdenverg, Adolpho Milech, Fariba Vaziri-Sani, José Egídio Paulo de Oliveira, Melanie Rodacki
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引用次数: 8

Abstract

Objective: Zinc transporter 8 autoantibodies (ZnT8A) have been poorly studied in non-Caucasian individuals. We aimed to investigate the prevalence of ZnT8 autoantibodies in patients with T1D and their first degree relatives (FDR) from a multiethnic population, as well as its relation with the insulin (INS) or the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene polymorphisms.

Subjects and methods: ZnT8A were analyzed in sera from T1D patients (n = 72, mean age of 30.3 ± 11.4 years) of variable duration (15.7 ± 11.8 years) and their FDR (n = 78, mean age of 18.3 ± 9.1 years) by a triple mix Radioligand Binding Assay (RBA) for the ZnT8 autoantibody (ZnT8-RWQ) variants. SNP (single nucleotide polymorphism) for INS and PTPN22 were genotyped.

Results: The prevalence of ZnT8A was higher in T1D patients than FDR, for ZnT8TripleA (24% vs. 4%,p = 0.001), ZnT8RA (24% vs. 4%, p < 0.001) and ZnT8QA (15% vs. 3%, p = 0.004). All FDR with ZnT8A (n = 3) had at least another positive antibody. Heterozygosis for PTPN22 was associated with a higher frequency of ZnT8TripleA (p = 0.039) and ZnT8RA (p = 0.038).

Conclusions: ZnT8A is observed in non-Caucasian patients with T1D, even years after the disease onset, as well as in their FDR. In those, there was an overlap between ZnT8A and other T1D antibodies. ZnT8A was associated with PTPN22 polymorphisms. Further longitudinal studies are necessary to elucidate the importance of these findings in the natural history of T1D patients with multiethnic background.

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多民族人群及其一级亲属1型糖尿病患者锌转运蛋白8自身抗体的研究
目的:锌转运蛋白8自身抗体(ZnT8A)在非白种人中的研究很少。我们旨在调查来自多种族人群的T1D患者及其一级亲属(FDR)中ZnT8自身抗体的患病率,以及它与胰岛素(INS)或蛋白酪氨酸磷酸酶非受体22 (PTPN22)基因多态性的关系。研究对象和方法:采用三混合放射配体结合试验(RBA)对不同病程(15.7±11.8年)的T1D患者(n = 72,平均年龄30.3±11.4岁)及其FDR (n = 78,平均年龄18.3±9.1岁)的ZnT8自身抗体(ZnT8- rwq)变体进行ZnT8A分析。对INS和PTPN22的单核苷酸多态性进行基因分型。结果:T1D患者中ZnT8A的患病率高于FDR, ZnT8TripleA(24%比4%,p = 0.001)、ZnT8RA(24%比4%,p < 0.001)和ZnT8QA(15%比3%,p = 0.004)。所有携带ZnT8A的FDR (n = 3)至少有另一种抗体阳性。PTPN22的杂合子与ZnT8TripleA (p = 0.039)和ZnT8RA (p = 0.038)的高频率相关。结论:在非高加索T1D患者中观察到ZnT8A,甚至在疾病发病数年后,以及他们的FDR。在这些病例中,ZnT8A和其他T1D抗体之间存在重叠。ZnT8A与PTPN22多态性相关。需要进一步的纵向研究来阐明这些发现在多种族背景的T1D患者自然史中的重要性。
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