Distinct genetic and immunological features in patients with onset of IDDM before and after age 40
Distinct genetic and immunological features in patients with onset of IDDM before and after age 40
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DOI：
10.2337/diacare.20.4.524
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发表时间：
1997-04-01
期刊：
影响因子：
16.2
通讯作者：
Scherbaum, WA
中科院分区：
文献类型：
--
作者：
Lohmann, T;Seissler, J;Scherbaum, WA
目的-发病年龄小是与胰岛素依赖型糖尿病快速进展相关的一个相关参数.我们的主要目的是确定诊断时年龄>40岁的IDDM患者与发病年龄较年轻的成年IDDM患者之间的差异。（胰岛细胞抗体[ICA]和GAD和酪氨酸磷酸酶IA 2的抗体[Ab]），在23名发病时年龄为12-38岁的IDDM患者（第1组）、24名发病时年龄>40岁的IDDM患者（第2组）、和12名健康对照受试者。采用间接免疫荧光法测定ICA，采用免疫沉淀法测定GAD-Ab和IA 2-Ab。通过5天增殖试验测试了针对GAD肽的T细胞应答，GAD肽已被鉴定为IDDM的典型肽。HLA结果：I型糖尿病患者中ICA和GAD抗体的检出率明显高于对照组（P < 0.001），但仅I型糖尿病1组有IA 2抗体（P <0.001），与I型糖尿病2组和对照组比较差异有显著性（P < 0.001）。此外，第1组和第2组的IDDM患者之间的抗体组合不同。对GAD肽的T细胞应答在IDDM 1组中为67%，在IDDM 2组中为71%（与对照组相比P < 0.02）。与第2组相比，第1组的IDDM患者DR 4（+）/DQ 8（+）的频率更高，而DR 2（+）/DQ 0602（+）的频率更低（P < 0.05）。结论：我们的数据提供了在40岁之前和之后发病的成年IDDM患者中存在体液和细胞自身免疫的强有力证据。然而，晚发性IDDM在抗体谱方面不同于初发性IDDM，特别是缺乏IA 2-Ab和HLA II类类型。这些发现对40岁以后确定慢性起病的胰岛素依赖型糖尿病的诊断策略具有重要意义。
OBJECTIVE - Young age at onset is a relevant parameter associated with a rapid progression of IDDM. Our major aim was to define differences between IDDM patients with age at diagnosis >40 years and adult IDDM with onset at a younger age.RESEARCH DESIGN AND METHODS - The correlation between islet-related antibodies (islet cell antibodies [ICAs] and antibodies [Abs] to GAD and the tyrosine phosphatase IA2), T-cell responses to GAD peptides and HLA class II isotypes was investigated in 23 IDDM patients 12-38 years of age at onset (group 1), 24 patients with IDDM >40 years of age at onset (group 2), and 12 healthy control subjects. ICAs were measured by indirect immunofluorescence, and GAD-Ab and IA2-Ab were measured by immunoprecipitation tests. T-cell responses against GAD peptides, which had been identified as typical for IDDM, were tested by 5-day proliferation assays. HLA. class II alleles were typed by polymerase chain reaction.RESULTS - ICAs and GAD-Abs were more prevalent in IDDM patients than in control subjects (P < 0.001), but only IDDM group 1 had IA2-Abs (P < 0.001 compared with IDDM group 2 and control subjects). Moreover, antibody combinations differed between IDDM patients of groups 1 and 2. T-cell responses to GAD peptides were seen in 67% of IDDM group 1 and in 71% of IDDM group 2 (P < 0.02 compared with control subjects). IDDM patients of group 1 were more frequently DR4(+)/DQ8(+) and less frequently DR2(+)/DQ0602(+) compared with IDDM patients of group 2 (P < 0.05).CONCLUSIONS - Our data provide strong evidence for humoral and cellular autoimmunity in adult IDDM patients with onset both before and after 40 years of age. However, late-onset differs from young-onset IDDM with respect to Ab profiles, especially a lack of IA2-Ab, and HLA class II types. These findings have consequences for the diagnostic strategy for identifying slow-onset IDDM in individuals after 40 years of age.