Baeva Maria-Elizabeth, Tottenham Isabelle, Koch Marcus, Camara-Lemarroy Carlos
Department of Clinical Neurosciences, University of Calgary, Canada; Hotchkiss Brain Institute, University of Calgary, Canada.
Department of Clinical Neurosciences, University of Calgary, Canada; Hotchkiss Brain Institute, University of Calgary, Canada.
J Neuroimmunol. 2024 Feb 15;387:578268. doi: 10.1016/j.jneuroim.2023.578268. Epub 2023 Dec 23.
To investigate serum biomarkers of progression in inactive primary progressive multiple sclerosis (PPMS).
We measured protein biomarkers (growth differentiation factor-15 (GDF-15), dickkopf-1 (DKK-1), neuron specific enolase (NSE) and cathepsin-D) in serum samples from 39 patients with inactive PPMS included in a clinical trial enrolling people with PPMS (clinicaltrials.gov identifier NCT02913157) and investigated the association of these biomarker levels with clinical disability at baseline and during follow-up. We then performed a meta-analysis of publicly available transcriptomic datasets to investigate the gene expression of these biomarkers in the CNS in progressive MS.
When compared with healthy controls, people with PPMS had higher serum levels of GDF-15, DKK-1 and cathepsin-D at baseline. These findings match those in our meta-analysis which found increased expression of GDF-15 and cathepsin-D in the CNS in progressive MS. At baseline, elevated serum DKK-1 was associated with worse Expanded Disability Status Scale (EDSS) and nine-hole peg test (9HPT) scores. None of the other biomarkers levels significantly correlated with EDSS, Timed 25-Foot Walk Test (T25FWT), 9HPT, or cognitive measures. However, serum GDF-15 and cathepsin-D were higher at baseline in participants who developed worsening disability. Our receiver operating characteristic curve showed that higher serum GDF-15 and cathepsin-D at baseline significantly discriminated between participants who worsened in T25FWT and 9HPT and those who remained stable.
Patients with PPMS have altered levels of GDF-15, DKK-1 and cathepsin-D in serum, and GDF-15 and cathepsin-D may have predictive value in progression free of inflammatory activity in PPMS.
研究非活动性原发性进行性多发性硬化症（PPMS）进展的血清生物标志物。
我们测量了参与一项纳入PPMS患者的临床试验（clinicaltrials.gov标识符NCT02913157）的39例非活动性PPMS患者血清样本中的蛋白质生物标志物（生长分化因子-15（GDF-15）、Dickkopf-1（DKK-1）、神经元特异性烯醇化酶（NSE）和组织蛋白酶-D），并研究了这些生物标志物水平与基线及随访期间临床残疾的相关性。然后，我们对公开可用的转录组数据集进行了荟萃分析，以研究这些生物标志物在进行性MS中枢神经系统中的基因表达。
与健康对照相比，PPMS患者在基线时血清GDF-15、DKK-1和组织蛋白酶-D水平较高。这些发现与我们的荟萃分析结果一致，该分析发现进行性MS中枢神经系统中GDF-15和组织蛋白酶-D的表达增加。在基线时，血清DKK-1升高与扩展残疾状态量表（EDSS）和九孔插针试验（9HPT）评分较差相关。其他生物标志物水平均与EDSS、25英尺计时步行试验（T25FWT）、9HPT或认知指标无显著相关性。然而，残疾恶化的参与者在基线时血清GDF-15和组织蛋白酶-D较高。我们的受试者工作特征曲线显示，基线时较高的血清GDF-15和组织蛋白酶-D能显著区分T25FWT和9HPT恶化的参与者与保持稳定的参与者。
PPMS患者血清中GDF-15、DKK-1和组织蛋白酶-D水平发生改变，GDF-15和组织蛋白酶-D可能对PPMS无炎症活动的进展具有预测价值。
