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diagnosis of alzheimer's disease by analysis of il - 10 gene polymorphisms

机译：il-10基因多态性分析诊断阿尔茨海默病;

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An inflammatory process is suggested to be involved in the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder characterized by the presence of neuritic plaques within the cerebral cortex that are mainly composed of a small insoluble protein of 40-42 amino acids (amyloid protein). The biological correlates of this process are nevertheless not clear. Interleukin-10 (IL-10) is a cytokine that suppresses T lymphocytes and cell-mediated immunity in humans and mice and has potent anti-inflammatory properties. To verify if IL-10 production would be impaired in AD patients we stimulated PBMC of 47 patients and 25 age-matched healthy controls (HC) with a mitogen, a recall antigen or with amyloid peptides. IL-2 production was measured as well in the same cultural conditions. Results showed that amyloid-specific IL-10 generation is selectively and significantly reduced in AD patients (p=0.023). Analyses on the alleles of the IL-10 gene revealed that the genotype associated with high IL-10 production is extremely infrequent in AD individuals (2% vs. 28%). The presence of low/intermediate IL-10-producing genotypes (GCC/ATA; ATA/ATA) was associated with an earlier age at disease onset and (ACC/ACC; ACC/ATA) with an accelerated rate of disease progression. These data shed light on the biology of the inflammatory process involved in the pathogenesis of AD by showing that the presence of low-IL-10-allelic isoforms results in an amyloid-specific impairment of IL-10 production and is associated with the clinical severity of AD. These results lend support to the use of anti-inflammatory compounds in the therapy of this disease.

机译：炎症过程被认为与阿尔茨海默氏病（AD）的发病机理有关，AD是一种神经退行性疾病，其特征在于大脑皮层中存在神经斑，其主要由40-42个氨基酸的小不溶蛋白组成（淀粉样蛋白）。然而，该过程的生物学关联尚不清楚。白细胞介素10（IL-10）是一种抑制人和小鼠T淋巴细胞和细胞介导的免疫力的细胞因子，具有有效的抗炎特性。为了验证在AD患者中IL-10的产生是否会受到损害，我们用促分裂原，召回抗原或淀粉样蛋白肽刺激了47位患者和25位年龄相匹配的健康对照（HC）的PBMC。在相同的培养条件下也测量了IL-2的产生。结果表明，AD患者中淀粉样蛋白特异性IL-10的生成有选择地显着降低（p = 0.023）。对IL-10基因的等位基因进行分析后发现，AD个体中与高IL-10产生相关的基因型极少发生（2％对28％）。低/中度产生IL-10的基因型（GCC / ATA; ATA / ATA）的存在与疾病发作的早期年龄有关（ACC / ACC; ACC / ATA）与疾病进展的速度加快有关。这些数据通过显示低IL-10等位基因亚型的存在会导致IL-10产生淀粉样蛋白特异性损伤，并与临床严重程度相关，从而揭示了AD发病机制中炎症过程的生物学机制。的。这些结果支持在该疾病的治疗中使用抗炎化合物。

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公开/公告号DE60329179D1

专利类型
公开/公告日2009-10-22

原文格式PDF
申请/专利权人 IMMUNOCLIN LTD.;
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申请/专利号DE20036029179T
发明设计人 CLERICI MARIO;ANNONI GIORGIO;
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申请日2003-05-30
分类号C12N15/09;C12Q1/68;A61K38;A61K38/19;A61K38/20;A61K45;A61K48;A61P3/10;A61P11/06;A61P19/02;A61P21/04;A61P25;A61P25/02;A61P25/16;A61P25/28;A61P29;A61P31/18;A61P37/02;A61P43;C12N15/24;C12Q1/6883;G01N33/68;G01N33/74;
国家 DE
入库时间 2022-08-21 19:07:45

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