成人隐匿性自身免疫糖尿病患者存在GAD65反应性T细胞免疫异常  

Abnormal T cell autoimmunity against GAD65 in LADA patients

作　　者：张翼[1] 周智广[2] 杨琳[2] 林健[2] 李霞[2] 何伟民[1] 

机构地区：[1]福建医科大学附属泉州第一医院,362100 [2]中南大学湘雅二医院内分泌科中南大学糖尿病中心中南大学代谢内分泌研究所,长沙

出　　处：《中华医学杂志》2010年第28期1963-1965,共3页National Medical Journal of China

基　　金：国家自然科学基金（30400217）;福建省科技厅青年人才项目（2006173145）;福建医科大学科研专项基金（FZS08003）;泉州市科技局重点项目资助（2007229）

摘　　要：目的探讨成人隐匿性自身免疫糖尿病（LADA）患者细胞水平的免疫发病机制。方法湖南省1型糖尿病协作中心2005年1至6月就诊的LADA患者17例，2004年3月至2006年1月就诊的2型糖尿病（T2DM）患者28例，健康者（对照）16名；放射配体法检测胰岛自身抗体；连续密度梯度离心法分离人外周血单个核细胞；酶联免疫斑点法检测谷氨酸脱羧酶（GAD65）反应性、Th1、Th2细胞，两者比值示为Th1／Th2平衡。结果LADA组较T2DM、对照组具有更多Th1细胞，LADA、T2DM及对照组的Th1细胞数分别为4．0、2．0及1．0个，差异有统计学意义（P〈0．01）；3组的Th2细胞分别为2．0、3．3及1．0个（P〉0．05）；3组的Th1／Th2比值分别为3．0、0．4及0．3，差异有统计学意义（P〈0．05）；T2DM组的Th1细胞及Th1／Th2比值均与对照组差异无统计学意义，3组对植物血凝素非特异性刺激的Th1、Th2细胞数差异无统计学意义（均P〉0．05）。结论LADA患者体内存在高频率的Th1细胞以及Th1／Th2平衡向Th1偏移是其细胞水平的免疫发病机制。Objective To explore the T cell-mediated immunopathogenesis of latent autoimmune diabetes in adults （LADA）. Methods Seventeen LADA patients, 28 T2DM （type 2 diabetes mellitus ） patients and 16 healthy controls were recruited. GAD-Ab, IA-2Ab and CPH-Ab were determined by radioligand assays. Human peripheral blood mononuelear cells were isolated by Ficoll-Hypaque density gradients. And the spot numbers of IFN-γ-secreting T cells （ IFN-γ-Th1 ） and IL-4-secreting T cells （ IL-4- Th2） were detected by enzyme linked immunospot （ELISPOT） assay. One spot-forming represented a GAD65-reactive IFN-γ/IL-4-seereting T cell. The ratio （balance） of Th1/Th2 was defined as IFN-γ-Th1/ IL-4-Th2. Results （ 1 ） The spot numbers of IFN-γ-Th1 （ median ） were 4. 0, 2. 0 and 1.0 in LADA, T2DM and control while those of IL-4-Th2 2. 0, 3.3 and 1.0 and Th1/Th2 3.0, 0. 4 and 0. 3 respectively; （2） As compared to T2DM or control group, significant increases of Th1 （P 〈0. 01 ） and Th1/Th2（P 〈 0. 05 ） were observed in LADA group. But the spot numbers of Th2 showed no significant differences among three groups （P 〉0. 05）. And there were no differences of Th1 and Th1/Th2 between T2DM and control group （ P 〉 0. 05 ） ; （ 3 ） No significant difference of Th1 or Th2 was observed for phytohemagglutinin （PHA） stimulation in three groups （P 〉 0.05 ）. Conclusions Significantly enhanced IFN-γ-Th1 cells and a shift of Th1/Th2 towards Th1 are present in LADA patients. They may contribute to the T-cell mediated immunopathogenesis of LADA.

关 键 词：糖尿病 1型 免疫 细胞 T淋巴细胞 酶联免疫斑点试验 

分 类 号：R587.1[医药卫生—内分泌]