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1 型糖尿病患儿及其兄弟姐妹的自然杀伤细胞比例较低。

Lower percentages of natural killer cells in children with type 1 diabetes and their siblings.

机构信息

Department of Paediatric Endocrinology and Diabetology with Laboratory of Endocrinology and Metabolism, Medical University of Lublin, Poland.

出版信息

Pediatr Endocrinol Diabetes Metab. 2023;29(4):214-224. doi: 10.5114/pedm.2023.132029.

Abstract

INTRODUCTION

One of the most common children's endocrine and autoimmune diseases in the world is type 1 diabetes mellitus (T1DM). The incidence of type 1 diabetes is constantly increasing, and according to current estimates, the number of children with T1DM in the world has exceeded 542,000. There are 3 main components emphasized in the pathogenesis: genetic and environmental factors, and the patient's immune system. Many publications have confirmed the role of natural killer cells (NK) in the pathogenesis of type 1 diabetes and other autoimmune diseases.

AIM

The aim of the study was to evaluate the population of NK cells and pancreatic β cell autoantibodies in a group of children with T1DM and their healthy siblings in comparison with children from families with no history of autoimmune diseases.

MATERIAL AND METHODS

The research included 76 children with T1DM, 101 children from the sibling group, and 30 children from the control group. Peripheral blood was analysed on a FACSCalibur flow cytometer (Becton Dickinson) to evaluate the NK cell population. The results were presented as the percentage of NK cells among lymphocytes. Statistical analysis was performed using STATIS-TICA 10 PL software.

RESULTS

The mean percentage of NK cells in children with T1D (10.59 ±5.37) and in the sibling group (11.93 ±5.62) was statistically reduced in comparison to the control group (14.89 ±7.78) in sequence (Student's t -test: t = -3.24; df = 103; p = 0.002) (Stu-dent's t -test: t = -2.30; df = 128; p = 0.02). There was no statistically significant difference in the percentage of NK cells be-tween the group of children with T1DM and their siblings (Student's t -test: t = -1.59; df = 173; p = 0.11). In the group of sib-lings, the younger the child, the lower the reported percentage of NK cells. This relationship was statistically significant (test for the Pearson correlation coefficient t = 3.41; p = 0.0009; r = 0.33). In the group of children with type 1 diabetes, a similar relationship was not found. The concentration of anti-IA2 and anti-Znt8 antibodies was statistically significantly higher in the sibling group compared to the control group (anti-IA2 p = 0.0000001; anti-ZnT8 p = 0.00001), and the concentration of anti-GAD antibodies was comparable in both groups. In the group of children with type 1 diabetes, a positive correlation was demonstrated between the reduced percentage of NK cells and the coexistence of anti-GAD and anti-ZnT8 antibodies (Mann-Whitney U test Z = -2.02; p = 0.04). There was no similar relationship in the group of siblings.

CONCLUSIONS

The reduced percentage of NK cells in children with T1DM and in their siblings compared to the control group suggests the role of NK cells in the pathogenesis of T1DM. Genetic predisposition and dysfunction of NK cells probably underlie the pathogenesis of T1DM.

摘要

简介

1 型糖尿病(T1DM)是世界上最常见的儿童内分泌和自身免疫性疾病之一。1 型糖尿病的发病率不断上升,根据目前的估计,全世界儿童 T1DM 患者已超过 54.2 万。发病机制强调了 3 个主要组成部分:遗传和环境因素以及患者的免疫系统。许多出版物已经证实自然杀伤细胞(NK)在 1 型糖尿病和其他自身免疫性疾病的发病机制中的作用。

目的

本研究旨在评估一组 T1DM 患儿及其健康兄弟姐妹与无自身免疫性疾病家族史的儿童的 NK 细胞群和胰岛β细胞自身抗体。

材料与方法

研究纳入了 76 例 T1DM 患儿、101 例同胞组患儿和 30 例对照组患儿。使用 FACSCalibur 流式细胞仪(Becton Dickinson)分析外周血,评估 NK 细胞群。结果以 NK 细胞占淋巴细胞的百分比表示。使用 STATISTICA 10 PL 软件进行统计分析。

结果

与对照组(14.89 ±7.78)相比,T1D 患儿(10.59 ±5.37)和同胞组患儿(11.93 ±5.62)的 NK 细胞百分比均明显降低(学生 t 检验:t = -3.24;df = 103;p = 0.002)(学生 t 检验:t = -2.30;df = 128;p = 0.02)。T1DM 患儿与同胞组患儿之间的 NK 细胞百分比无统计学差异(学生 t 检验:t = -1.59;df = 173;p = 0.11)。在同胞组中,儿童年龄越小,报告的 NK 细胞百分比越低。这种关系具有统计学意义(Pearson 相关系数 t 检验:t = 3.41;p = 0.0009;r = 0.33)。在 T1DM 患儿组中,未发现类似的关系。与对照组相比,同胞组的 IA2 抗体和 ZnT8 抗体浓度明显升高(IA2 抗体 p = 0.0000001;ZnT8 抗体 p = 0.00001),而两组的 GAD 抗体浓度相似。在 T1DM 患儿组中,NK 细胞百分比降低与 GAD 和 ZnT8 抗体共存之间呈正相关(Mann-Whitney U 检验 Z = -2.02;p = 0.04)。在同胞组中没有类似的关系。

结论

与对照组相比,T1DM 患儿及其同胞的 NK 细胞百分比降低提示 NK 细胞在 T1DM 发病机制中的作用。遗传易感性和 NK 细胞功能障碍可能是 T1DM 发病机制的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4661/10826694/342f4c9384d4/PEDM-29-51638-g001.jpg

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