Department of Pediatrics, Medical University of Warsaw, Warsaw, Poland.
Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Medical University of Warsaw, Warsaw, Poland.
Adv Med Sci. 2014 Mar;59(1):39-43. doi: 10.1016/j.advms.2013.07.003. Epub 2014 Mar 15.
Despite the rapidly rising incidence of diabetes in children, with the highest rise in children<5 years of age, data on mechanisms that trigger severe beta-cells damage are limited. The aim of the study was to assess the frequency of OX40 (CD134) or 4-1BB (CD137) positive cells in the peripheral blood of children with newly diagnosed type 1 diabetes (T1D) in comparison to healthy controls.
MATERIAL/METHODS: The study included 33 children (mean age 7.3 ± 5.4 years) with newly diagnosed T1D and 39 age-matched healthy controls. Separate analysis was performed in children<5 years. Flow cytometric analysis was performed using the following markers: CD4, CD25, CD137, and CD134. Fasting C-peptide level was assessed as well.
The frequency of CD4(+)CD25(high)OX40(+) was higher in T1D children than in controls (median value 3.58% vs. 1.1%, respectively; p=0.003). Moreover, T1D children had higher frequency of CD4(+)CD25(high)4-1BB(+) cells than healthy subjects (median value 5.76% vs. 3.74%, respectively; p=0.037). A significant correlation was noted between the age of diabetic children and the C-peptide level (r=0.54, 95% CI [0.19-0.77], p=0.004). In comparison with age-matched controls, children<5 years had higher frequency of CD4(+)CD25(high)OX40(+) (p=0.004) and CD4(+)CD25(high)4-1BB(+) cells (p=0.079).
Our study showed higher frequency of both OX40 and 4-1BB positive cells in T1D children in comparison to controls. It seems that observed differences might be more pronounced in children<5 years of age than in older subjects. Further clinical studies are needed to determine the age-related differences in the immune system, in the pathogenesis of T1D.
尽管儿童糖尿病的发病率迅速上升，其中<5 岁儿童的发病率上升最快，但导致严重β细胞损伤的机制数据有限。本研究旨在评估新诊断的 1 型糖尿病（T1D）患儿外周血中 OX40（CD134）或 4-1BB（CD137）阳性细胞的频率，并与健康对照组进行比较。
材料/方法：本研究纳入了 33 名（平均年龄 7.3±5.4 岁）新诊断为 T1D 的儿童和 39 名年龄匹配的健康对照者。<5 岁的儿童单独进行了分析。采用流式细胞术分析以下标志物：CD4、CD25、CD137 和 CD134。同时评估空腹 C 肽水平。
与对照组相比，T1D 患儿的 CD4(+)CD25(high)OX40(+)频率更高（中位数分别为 3.58%和 1.1%；p=0.003）。此外，与健康受试者相比，T1D 患儿的 CD4(+)CD25(high)4-1BB(+)细胞频率更高（中位数分别为 5.76%和 3.74%；p=0.037）。糖尿病患儿的年龄与 C 肽水平呈显著相关性（r=0.54，95%CI[0.19-0.77]，p=0.004）。与年龄匹配的对照组相比，<5 岁的儿童的 CD4(+)CD25(high)OX40(+)频率更高（p=0.004），CD4(+)CD25(high)4-1BB(+)细胞频率也更高（p=0.079）。
与对照组相比，我们的研究显示 T1D 患儿的 OX40 和 4-1BB 阳性细胞频率更高。在<5 岁的儿童中，观察到的差异似乎比在年龄较大的儿童中更为明显。需要进一步的临床研究来确定免疫系统在 T1D 发病机制中的年龄相关差异。
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