阿尔茨海默病患者外周血Aβ抗体和细胞因子的变化

Changes of Aβ antibody and cytokines in peripheral blood from patients with Alzheimer’s disease

目的探讨阿尔茨海默病（AD）患者外周免疫功能的变化。方法以2006-06-2007-04广州市老人院29例AD患者作为观察对象,其中轻中度AD患者19例,重度10例;对照组19例为同期健康老人。用夹心酶联免疫吸附法（ELISA）测定外周血Aβ抗体以及抗原特异性细胞因子的水平;流式细胞术（FACS）检测外周血淋巴细胞亚群变化;酶联免疫吸附斑点试验（ELISPOT）检测抗原特异性细胞因子的分泌细胞频数。结果轻中度和重度AD组患者外周血A4β2抗体水平较对照组有不同程度的下降（分别为P〈0.05,P〈0.01）。AD组CD8较对照组显著升高（P〈0.05）;CD4较对照组显著降低（P〈0.05）;轻中度和重度AD组之间CD8、CD4及CD4/CD8差异均无统计学意义（P〉0.05）。AD组外周血单核细胞（PBMC）培养上清IFN-γ的含量较对照组降低（P〈0.05）,以重度AD组更明显。ELISPOT检测结果,AD组每4×105个PBMC中分泌IFN-γ的细胞频数较对照组显著减少（P〈0.01）,以重度AD患者更为明显。结论AD患者外周血Aβ抗体水平下降;淋巴细胞亚群失调,特异性细胞免疫功能受损。

Objective To observe changes of peripheral immune function in patients with Alzheimer＇ s disease and to investigate their clinical meanings. Methods A total of 48 cases in Guangzhou Welfare Center from June 2006 to April 2007 were consecutively selected as the observed subjects, including 19 mild to moderately severe AD patients, 10 severe AD patients and 19 healthy age-matched controls. Level of the anti-β-amyloid peptide antibody was detected by ELISA. Distribution of the T-, B-cell subsets was determined by flow cytometry （ FACS）. The production of IFN-γ and IL-4 by peripheral blood mononuclear cell （PBMC） after stimulation with 1-42 beta-amyloid （Aβ） fragments was also evaluated by ELISA and ELISPOT. Results Compared to the controls, the levels of Aβ42 antibody in serum in the patients with different course of AD were significant decreased （ P 〈 0.05 and P 〈 0. 01, respectively）. The levels of CDs in peripheral blood from patients with different degree of AD were upregulated to some extent（ P 〈 0.05 ） ; In conurast, CD4 were significant down-regulated （ P 〈 0.05 ） ; After stimulated with antigen Aβ42, the level of IFN-γ in the cultured medium of PBMC in HC was significant higher than that in both AD groups （ P 〈 0.05）. After stimulated with antigen Aβ42, in every 4 ×10^5 PBMCs, the numbers of IFN-γ secreting ceils in HC was significantly more than that in both AD groups （ P 〈 0.01 ）. Conclusion Our observations found a highly significant decrease of Aβ1-42 antibody in AD patients, and the observed imbalance of immune peripheral cell subpopulations and decreased IFN-γ production point to an association of faulty immune regulation in AD.