St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
Keenan Research Centre for Biomedical Science, Unity Health Toronto, Toronto, ON, Canada.
Mult Scler. 2023 Oct;29(11-12):1373-1382. doi: 10.1177/13524585231195861. Epub 2023 Sep 12.
Granulocyte-macrophage colony stimulating factor (GM-CSF) is a pro-inflammatory cytokine secreted by various immune cells. Several studies have demonstrated an expansion of GM-CSF producing T cells in the blood or CSF of people with MS (pwMS). However, whether this equates to greater concentrations of circulating cytokine remains unknown as quantification is difficult with traditional assays.
To determine whether GM-CSF can be quantified and whether GM-CSF levels are elevated in pwMS.
We employed Single Molecule Array (Simoa) to measure GM-CSF in both CSF and blood. We then investigated relationships between GM-CSF levels and measures of blood-CSF-barrier integrity.
GM-CSF was quantifiable in all samples and was significantly higher in the CSF of pwMS compared with controls. No association was found between CSF GM-CSF levels and Q-Albumin - a measure of blood-CSF-barrier integrity. CSF GM-CSF correlated with measures of intrathecal inflammation, and these relationships were greater in primary progressive MS compared with relapsing-remitting MS.
GM-CSF levels are elevated specifically in the CSF of pwMS. Our results suggest that elevated cytokine levels may reflect (at least partial) intrathecal production, as opposed to simple diffusion across a dysfunctional blood-CSF-barrier.
粒细胞-巨噬细胞集落刺激因子（GM-CSF）是一种由各种免疫细胞分泌的促炎细胞因子。几项研究表明，多发性硬化症（pwMS）患者的血液或脑脊液中存在 GM-CSF 产生 T 细胞的扩增。然而，由于传统检测方法难以定量，目前尚不清楚这是否等同于循环细胞因子浓度的增加。
确定 GM-CSF 是否可以定量，以及 pwMS 中 GM-CSF 水平是否升高。
我们采用单分子阵列（Simoa）来测量 CSF 和血液中的 GM-CSF。然后，我们研究了 GM-CSF 水平与血液-脑脊液屏障完整性测量值之间的关系。
所有样本均能定量检测到 GM-CSF，且 pwMS 患者的 CSF 中 GM-CSF 水平明显高于对照组。CSF GM-CSF 水平与 Q-白蛋白（一种血液-脑脊液屏障完整性的测量值）之间没有关联。CSF GM-CSF 与鞘内炎症的测量值相关，在原发性进行性 MS 中，这些相关性比复发缓解性 MS 更大。
pwMS 患者的 CSF 中 GM-CSF 水平升高。我们的结果表明，升高的细胞因子水平可能反映（至少部分）鞘内产生，而不是穿过功能失调的血液-脑脊液屏障的简单扩散。
