Levels of Interleukin-6 in Saliva, but Not Plasma, Correlate with Clinical Metrics in Huntington's Disease Patients and Healthy Control Subjects.

Levels of Interleukin-6 in Saliva, but Not Plasma, Correlate with Clinical Metrics in Huntington's Disease Patients and Healthy Control Subjects.
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DOI:
10.3390/ijms21176363
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发表时间:
2020-09-02
影响因子:
5.6
通讯作者:
Thomas EA
Thomas EA
中科院分区:
生物学2区
文献类型:
--
作者:
Corey-Bloom J;Fischer RS;Kim A;Snell C;Parkin GM;Granger DA;Granger SW;Thomas EA

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越来越多的证据表明,脑和外周组织中的炎症反应导致亨廷顿病(HD)的疾病病理学,亨廷顿病是一种遗传性、进行性神经变性疾病,通常影响30-40岁的成年人。因此,外周液中炎症相关标志物的研究可能有助于更好地表征疾病特征。在这项研究中,我们使用免疫测定法测量了125名受试者唾液和血浆中的C-反应蛋白(CRP)、白细胞介素-6(IL-6)、白细胞介素1 β(IL-1B)和α-淀粉酶(AA)水平,其中包括37名显性HD患者、36名预显性患者和52名健康对照。我们发现不同疾病组的唾液中IL-6、IL-1B和CRP水平升高,HD患者血浆中IL-6水平升高,与预表现患者和对照组相比。唾液IL-6水平与其他唾液标志物中的每一种以及血浆中测量的IL-6水平显著相关。此外,唾液IL-6和IL-1B水平与HD患者的总运动评分(TMS)和舞蹈病评分显著正相关,与总功能能力(TFC)呈负相关,而在健康对照受试者中,IL-6与蒙特利尔认知评估(莫卡)和符号数字模式测试(SDM)显著负相关。有趣的是,在HD或对照受试者中,IL-6的血浆水平与任何临床测量均未显示出类似的相关性。这些发现表明,唾液IL-6作为HD症状的潜在非侵入性生物标志物特别相关。一种有效、可靠的唾液生物标志物的出现将满足对一种侵入性较小的方法来识别和监测HD疾病进展的迫切需求。
Growing evidence suggests that inflammatory responses, in both the brain and peripheral tissues, contribute to disease pathology in Huntington’s disease (HD), an inherited, progressive neurodegenerative disorder typically affecting adults in their 30–40 s. Hence, studies of inflammation-related markers in peripheral fluids might be useful to better characterize disease features. In this study, we measured levels of C-reactive protein (CRP), Interleukin-6 (IL-6), interleukin 1 beta (IL-1B), and alpha-amylase (AA) in saliva and plasma from n = 125 subjects, including n = 37 manifest HD patients, n = 36 premanifest patients, and n = 52 healthy controls, using immunoassays. We found increases in salivary levels of IL-6, IL-1B and CRP across different disease groups and increased levels of IL-6 in the plasma of HD patients as compared to premanifest patients and controls. The levels of salivary IL-6 were significantly correlated with each of the other salivary markers, as well as with IL-6 levels measured in plasma. Further, salivary IL-6 and IL-1B levels were significantly positively correlated with Total Motor Score (TMS) and chorea scores and negatively correlated with Total Functional Capacity (TFC) in HD patients, whereby in healthy control subjects, IL-6 was significantly negatively correlated with Montreal Cognitive Assessment (MoCA) and the Symbol Digit Modalities test (SDM). Interestingly, the plasma levels of IL-6 did not show similar correlations to any clinical measures in either HD or control subjects. These findings suggest that salivary IL-6 is particularly relevant as a potential non-invasive biomarker for HD symptoms. The advent of an effective, dependable salivary biomarker would meet the urgent need for a less invasive means of identifying and monitoring HD disease progression.
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