Department of Clinical Chemistry, Amsterdam University Medical Centre, Amsterdam, The Netherlands.
Department of Neurology, Amsterdam University Medical Centre, Amsterdam, The Netherlands.
Ann Clin Transl Neurol. 2019 Sep;6(9):1582-1594. doi: 10.1002/acn3.771. Epub 2019 Jul 31.
The pathophysiology of multiple sclerosis disease progression remains undetermined. The aim of this study was to identify differences in plasma proteome during different stages of MS disease progression.
We used a multiplex aptamer proteomics platform (Somalogic) for sensitive detection of 1129 proteins in plasma. MS patients were selected and categorized based on baseline and a 4-year follow-up EDSS (delta EDSS) scores; relapse-onset (RO) slow progression (n = 31), RO with rapid progression (n = 29), primary progressive (n = 30), and healthy controls (n = 20). The relation of baseline plasma protein levels with delta EDSS and different MRI progression parameters were assessed using linear regression models.
Regression analyses of plasma proteins with delta EDSS showed six significant associations. Strong associations were found for the proteins LGLAS8 (P = 7.64 × 10 , q = 0.06), CCL3 (P = 0.0001, q = 0.06), and RGMA (P = 0.0005, q = 0.09). In addition, associations of plasma proteins were found with percentage brain volume for C3 (P = 2,08 × 10 , q = 1,70 × 10 ), FGF9 (P = 3,42 × 10 , q = 1,70 × 10 ), and EHMT2 (P = 0.0007, q = 0.01). Most of the significant markers were associated with cell-cell and cell-extracellular matrix adhesion, immune system communication, immune system activation, and complement pathways.
Our results revealed eight novel biomarkers related to clinical and radiological progression in MS. These results indicate that changes in immune system, complement pathway and ECM remodeling proteins contribute to MS progression and may therefore be further explored for use in prognosis of MS.
多发性硬化症疾病进展的病理生理学仍未确定。本研究的目的是确定多发性硬化症疾病进展不同阶段的血浆蛋白质组差异。
我们使用了一种多重适体蛋白质组学平台（Somalogic）来敏感地检测血浆中的 1129 种蛋白质。根据基线和 4 年随访的 EDSS（delta EDSS）评分，选择和分类多发性硬化症患者；复发缓解型（RO）缓慢进展（n=31）、RO 快速进展（n=29）、原发性进展型（n=30）和健康对照组（n=20）。使用线性回归模型评估基线血浆蛋白水平与 delta EDSS 以及不同 MRI 进展参数之间的关系。
对 delta EDSS 的血浆蛋白回归分析显示有 6 个显著关联。LGLAS8（P=7.64×10，q=0.06）、CCL3（P=0.0001，q=0.06）和 RGMA（P=0.0005，q=0.09）蛋白与 delta EDSS 的关联非常强烈。此外，C3（P=2.08×10，q=1.70×10）、FGF9（P=3.42×10，q=1.70×10）和 EHMT2（P=0.0007，q=0.01）等血浆蛋白的关联与脑容量百分比相关。大多数显著标志物与细胞-细胞和细胞-细胞外基质黏附、免疫系统通讯、免疫系统激活和补体途径有关。
我们的研究结果揭示了与多发性硬化症临床和影像学进展相关的 8 种新型生物标志物。这些结果表明，免疫系统、补体途径和细胞外基质重塑蛋白的变化导致多发性硬化症的进展，因此可能进一步用于多发性硬化症的预后。
