Department of Neurology, Technische Universität Dresden, Dresden, Germany.
Center for Clinical Neuroscience, University Hospital Carl Gustav Carus, Dresden, Germany.
Sci Rep. 2020 Apr 3;10(1):5941. doi: 10.1038/s41598-020-62756-8.
Neuroinflammation is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS), but only limited data are available on systematic peripheral and central immune cell profiles in ALS. We studied detailed immune profiles of 73 ALS patients and 48 healthy controls (controls) in peripheral blood by fluorescence-activated cell sorting as well as cytokine expression profiles in serum. In a subgroup of 16 ALS patients and 10 controls we additionally studied cerebrospinal fluid (CSF) samples. In peripheral blood, T cell subtypes presented a shift towards pro-inflammatory Th 1 and Th 17 cells whereas anti-inflammatory Th2 and T regulatory cells were decreased. Important players in innate immunity including distinct monocyte (Mo) and natural killer (NK) cell subtypes were changed in ALS patients compared to controls. Pro-inflammatory serum cytokines such as interleukin (IL)-1 beta, IL-6 and interferon-gamma (IFN-gamma) were increased and the anti-inflammatory cytokine IL-10 was decreased. Correlation analysis revealed moderate negative correlations between Th1 and Th17 to the ALS functional rating scale revised (ALSFRS-R) and to forced vital capacity. In CSF samples, no relevant alteration of the immune profile was found. In conclusion, the immune profile in ALS was shifted towards a Th1/Th17 cell-mediated pro-inflammatory immune response and correlated to disease severity and progression. Large prospective studies are needed to confirm these findings.
神经炎症参与肌萎缩侧索硬化症（ALS）的发病机制，但关于 ALS 系统外周和中枢免疫细胞谱的有限数据。我们通过荧光激活细胞分选研究了 73 名 ALS 患者和 48 名健康对照者（对照组）外周血中的详细免疫谱，以及血清中细胞因子表达谱。在 16 名 ALS 患者和 10 名对照组的亚组中，我们还研究了脑脊液（CSF）样本。在外周血中，T 细胞亚型向促炎 Th1 和 Th17 细胞倾斜，而抗炎 Th2 和 T 调节细胞减少。与对照组相比，固有免疫中的重要参与者，包括不同的单核细胞（Mo）和自然杀伤（NK）细胞亚型，在 ALS 患者中发生了改变。促炎血清细胞因子，如白细胞介素（IL）-1β、IL-6 和干扰素-γ（IFN-γ）增加，抗炎细胞因子 IL-10 减少。相关性分析显示，Th1 和 Th17 与肌萎缩侧索硬化功能评定量表修订版（ALSFRS-R）和用力肺活量呈中度负相关。在 CSF 样本中，未发现免疫谱的相关改变。总之，ALS 中的免疫谱向 Th1/Th17 细胞介导的促炎免疫反应倾斜，并与疾病严重程度和进展相关。需要进行大型前瞻性研究来证实这些发现。
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