From the Department of Biomedicine (A.A., M.C., C.F.), University of Basel; Neurologic Clinic and Policlinic (C.B., J.O., L.K., Y.N., J.K., M.M.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel; Medical Image Analysis Center Basel AG (M.A.); Division of Neuroradiology (M.A.), University Hospital Basel; Department of Biomedical Engineering (M.A.), University Basel, Switzerland; and Department of Gynaecology (J.W.), University Hospital Würzburg, Germany.
Neurol Neuroimmunol Neuroinflamm. 2020 Feb 5;7(2). doi: 10.1212/NXI.0000000000000675. Print 2020 Mar 5.
To assess whether serum concentrations of the anti-inflammatory cytokine growth differentiation factor 15 (GDF-15) differ in patients with highly active multiple sclerosis (MS) vs patients with stable MS and healthy controls (HCs).
GDF-15 concentrations were measured by ELISA in serum and CSF in a cross-sectional cohort of patients with MS, patients with other inflammatory neurologic diseases (OIND), patients with noninflammatory neurologic diseases (NIND), and healthy controls (HC). Serum GDF-15 concentrations were measured in a longitudinally sampled cohort of clinically and radiologically well-characterized patients with MS and corresponding controls.
Cross-sectionally measured median serum GDF-15 concentrations were significantly higher in patients with OIND (n = 42) (600 pg/mL, interquartile range [IQR] = 320-907 pg/mL) compared with HCs (n = 29) (325 pg/mL, IQR = 275-419 pg/mL; = 0.0007), patients with NIND (n = 46) (304 pg/mL, IQR = 245-493 pg/mL; = 0.0002), or relapsing MS (n = 42) (356 pg/mL, IQR = 246-460 pg/mL; = 0.0002). CSF and serum concentrations of GDF-15 were correlated (r = 0.41, 95% CI = 0.25-0.56, < 0.0001). In a longitudinally sampled cohort of patients with MS (n = 48), deeply phenotyped with quantitative clinical and MRI assessments, mean GDF-15 concentrations were significantly higher in patients with a stable disease course (405 pg/mL, SD = 202) than in patients with intermittent MRI activity (333 pg/mL, SD = 116; = 0.02).
Serum GDF-15 concentrations are increased in patients with MS with a stable disease course. These data suggest that GDF-15 may serve as a biomarker for disease stability in MS.
评估在活动期多发性硬化症(MS)患者与稳定期 MS 患者和健康对照者(HC)之间,抗炎细胞因子生长分化因子 15(GDF-15)的血清浓度是否存在差异。
通过酶联免疫吸附试验(ELISA)在 MS 患者、其他炎症性神经疾病(OIND)患者、非炎症性神经疾病(NIND)患者和健康对照者(HC)的血清和脑脊液中测量 GDF-15 浓度。对具有明确临床和放射学特征的 MS 患者和相应对照者进行纵向采样队列,测量血清 GDF-15 浓度。
OIND(n=42)患者的血清 GDF-15 浓度中位数(600 pg/ml,四分位距 [IQR]=320-907 pg/ml)显著高于 HC(n=29)(325 pg/ml,IQR=275-419 pg/ml;=0.0007)、NIND(n=46)(304 pg/ml,IQR=245-493 pg/ml;=0.0002)或复发型 MS(n=42)(356 pg/ml,IQR=246-460 pg/ml;=0.0002)患者。GDF-15 的脑脊液和血清浓度呈正相关(r=0.41,95%置信区间 [CI]=0.25-0.56,<0.0001)。在 MS 患者的纵向采样队列中(n=48),通过定量临床和 MRI 评估对其进行了深入表型分析,具有稳定疾病过程的患者的平均 GDF-15 浓度(405 pg/ml,标准差 [SD]=202)显著高于间歇性 MRI 活动的患者(333 pg/ml,SD=116;=0.02)。
稳定疾病过程 MS 患者的血清 GDF-15 浓度升高。这些数据表明,GDF-15 可能作为 MS 疾病稳定的生物标志物。