Wild Edward, Magnusson Anna, Lahiri Nayana, Krus Ulrika, Orth Michael, Tabrizi Sarah J, Björkqvist Maria
UCL Institute of Neurology, London, UK; Bristol University, UK; Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK; Lund University Diabetes Center Malmö Sweden and Department of Neurology, University of Ulm, Ulm, Germany.
PLoS Curr. 2011 Apr 13;3:RRN1231. doi: 10.1371/currents.RRN1231.
Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities. Immune activation is a well-established feature of the HD brain and we have previously demonstrated a widespread, progressive innate immune response detectable in plasma throughout the course of HD. In the present work we used multiplex ELISA to quantify levels of chemokines in plasma from controls and subjects at different stages of HD. We found an altered chemokine profile tracking with disease progression, with significant elevations of five chemokines (eotaxin-3, MIP-1β, eotaxin, MCP-1 and MCP-4) while three (eotaxin-3, MIP-1β and eotaxin) showed significant linear increases across advancing disease stages. We validated our results in a separate sample cohort including subjects at different stages of HD. Here we saw that chemokine levels (MCP-1 and eotaxin) correlated with clinical scores. We conclude that, like cytokines, chemokines may be linked to the pathogenesis of HD, and that immune molecules may be valuable in tracking and exploring the pathogenesis of HD.
亨廷顿舞蹈症（HD）是一种遗传性神经退行性疾病，其特征为神经和全身异常。免疫激活是HD大脑的一个公认特征，我们之前已经证明，在HD病程中，血浆中可检测到广泛的、进行性的先天免疫反应。在本研究中，我们使用多重酶联免疫吸附测定（ELISA）来量化对照人群以及HD不同阶段受试者血浆中的趋化因子水平。我们发现趋化因子谱随疾病进展而改变，五种趋化因子（嗜酸性粒细胞趋化因子-3、巨噬细胞炎性蛋白-1β、嗜酸性粒细胞趋化因子、单核细胞趋化蛋白-1和单核细胞趋化蛋白-4）显著升高，而其中三种（嗜酸性粒细胞趋化因子-3、巨噬细胞炎性蛋白-1β和嗜酸性粒细胞趋化因子）在疾病进展阶段呈显著线性增加。我们在另一个包括HD不同阶段受试者的样本队列中验证了我们的结果。在此我们发现趋化因子水平（单核细胞趋化蛋白-1和嗜酸性粒细胞趋化因子）与临床评分相关。我们得出结论，与细胞因子一样，趋化因子可能与HD的发病机制有关，并且免疫分子在追踪和探索HD的发病机制方面可能具有重要价值。
