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维生素 D 血浆水平和维生素 D 相关遗传多态性对 1 型糖尿病患者免疫状态的影响:一项初步研究。

Influence of the vitamin D plasma level and vitamin D-related genetic polymorphisms on the immune status of patients with type 1 diabetes: a pilot study.

机构信息

Pharmazentrum Frankfurt/ZAFES, Frankfurt am Main, Germany.

出版信息

Clin Exp Immunol. 2013 Feb;171(2):171-85. doi: 10.1111/cei.12013.

Abstract

Vitamin D (VD) has been implicated in type 1 diabetes (T1D) by genetic and epidemiological studies. Individuals living in regions with low sunlight exposure have an increased T1D risk and VD supplementation reduced the risk in human individuals and mouse models. One possibility of how VD influences the pathogenesis of T1D is its immunomodulatory effect on dendritic cells (DC), which then preferentially activate regulatory T cells (T(regs) ). In the present pilot study, we collected blood samples from a small cohort of patients with T1D at baseline and months 6 and 12. VD-deficient patients were advised to supplement with 1000 IU/day VD. We found a considerable variation in the VD plasma level at baseline and follow-up. However, with higher VD plasma levels, a lower frequency of interleukin (IL)-4-producing CD8 T cells was observed. We further performed a comprehensive genotyping of 13 VD-related polymorphisms and found an association between VD plasma level and the genotype of the VD binding protein (DBP). The frequency of DC and T cell subsets was variable in patients of all subgroups and in individual patients over time. Nevertheless, we found some significant associations, including the 1,25-dihydroxyvitamin D(3) hydroxylase (CYP27B1) genotype with the frequency of DC subtypes. In summary, our preliminary results indicate only a limited influence of the VD plasma level on the immune balance in patients with T1D. Nevertheless, our pilot study provides a basis for a follow-up study with a larger cohort of patients.

摘要

维生素 D(VD)在 1 型糖尿病(T1D)的遗传和流行病学研究中被牵连。生活在阳光照射不足地区的个体 T1D 风险增加,VD 补充可降低人类和小鼠模型的风险。VD 影响 T1D 发病机制的一种可能性是其对树突状细胞(DC)的免疫调节作用,从而优先激活调节性 T 细胞(Tregs)。在本初步研究中,我们从一小群 T1D 患者基线和 6 个月和 12 个月时采集了血液样本。VD 缺乏症患者被建议每天补充 1000IU VD。我们发现基线和随访时 VD 血浆水平存在相当大的差异。然而,随着 VD 血浆水平的升高,IL-4 产生的 CD8 T 细胞的频率降低。我们进一步对 13 种与 VD 相关的多态性进行了全面基因分型,发现 VD 血浆水平与 VD 结合蛋白(DBP)的基因型之间存在关联。所有亚组患者和个体患者的 DC 和 T 细胞亚群的频率各不相同。尽管如此,我们发现了一些显著的关联,包括 1,25-二羟维生素 D(3)羟化酶(CYP27B1)基因型与 DC 亚型的频率之间存在关联。总之,我们的初步结果表明,VD 血浆水平对 T1D 患者的免疫平衡只有有限的影响。然而,我们的初步研究为更大队列患者的后续研究提供了基础。

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