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

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.

Abnormal T cell autoimmunity against GAD65 in LADA patients

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-reaetive IFN-γ/IL-4-secreting 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 cntrol 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.