血液捐献者中临床前期多发性硬化症的血浆神经丝轻链的时间动态变化。
Temporal Dynamics of Plasma Neurofilament Light in Blood Donors With Preclinical Multiple Sclerosis.
机构信息
From the The Danish Multiple Sclerosis Centre (J.B., H.B.S., M.M., J.L.F.B., F.S.), Department of Neurology, Copenhagen University Hospital, Rigshospitalet; Department of Clinical Immunology (J.B., M.H.L., S.R.O., S.M.), Copenhagen University Hospital Rigshospitalet; Department of Clinical Medicine (J.B., M.M., O.B.P., S.R.O., J.L.F.B., F.S., S.M.), Faculty of Health and Medical Sciences, University of Copenhagen; Department of Health Technology (A.G.P.), Section for Bioinformatics, Technical University of Denmark; The Danish Cancer Institute (S.R.), Statistics and Data Analysis; The Danish Multiple Sclerosis Registry (M.M.); Department of Clinical Immunology (O.B.P.), Zealand University Hospital; Department of Clinical Immunology (B.A.J.), Aalborg University Teaching Hospital; Department of Clinical Immunology (C.E.), Aarhus University Teaching Hospital and Statens Serum Institut (H.U.), Copenhagen, Denmark.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2025 Jan;12(1):e200335. doi: 10.1212/NXI.0000000000200335. Epub 2024 Nov 27.
BACKGROUND AND OBJECTIVES
Multiple sclerosis (MS) is a CNS disease, characterized by demyelination, inflammation, and neurodegeneration. Recent advances in technology allow measurement of the axonal damage marker neurofilament light chain in peripheral blood. Two studies have shown that patients with MS have elevated neurofilament light levels before their first symptom, but longitudinal studies are lacking. We aimed to investigate the intraindividual neurofilament light dynamics during the presymptomatic phase of MS.
METHODS
The Danish Blood Donor Study (DBDS) has stored plasma samples from blood donors for more than 10 years. We identified DBDS participants, who had subsequently been diagnosed with MS, and included all samples donated before their first demyelinating symptom (median 5.00 samples per case). As controls, we included 2 healthy donors per case. Plasma levels of neurofilament light were measured and compared with quality-of-life data. We used a Bayesian approach to derive estimates for the percentage of cases with presymptomatic increased neurofilament light levels.
RESULTS
We observed that 12 (17%, 95% CI 9%-28%) of 69 presymptomatic MS donors had intermittently increased neurofilament light levels preclinically. Increased levels were present up to 9 years before clinical onset, also in primary progressive MS. Healthy donors and presymptomatic MS donors with and without increased neurofilament light levels reported equally high physical and mental well-being. Model-based estimates suggested that 55% of cases (95% credible interval [28%-87%]) had experienced increased presymptomatic neurofilament light levels.
DISCUSSION
Patients with MS periodically sustain axonal injury up to 9 years before clinical onset, even in primary progressive disease. This most likely represents asymptomatic disease activity. Some or even all patients are affected by this intermittent axonal injury, prompting the need for further studies of the presymptomatic phase in relation to prognosis and as a therapeutic window of opportunity.
背景与目的
多发性硬化症（MS）是一种中枢神经系统疾病，其特征是脱髓鞘、炎症和神经退行性变。技术的最新进展使得可以在外周血液中测量轴突损伤标志物神经丝轻链。两项研究表明，MS 患者在出现首个症状之前就存在神经丝轻链水平升高，但缺乏纵向研究。我们旨在研究 MS 无症状期的个体内神经丝轻链动态。
方法
丹麦献血者研究（DBDS）保存了献血者的血浆样本已有 10 多年。我们确定了随后被诊断为 MS 的 DBDS 参与者，并纳入了所有在首次脱髓鞘症状前捐献的样本（每例中位数 5.00 个样本）。作为对照，我们每例纳入 2 名健康献血者。测量了神经丝轻链的血浆水平，并与生活质量数据进行了比较。我们使用贝叶斯方法来推导无症状期神经丝轻链水平升高的病例比例的估计值。
结果
我们发现，69 名无症状 MS 供体中有 12 名（17%，95%CI 9%-28%）在临床前间歇性地出现神经丝轻链水平升高。升高的水平在临床发病前最多可提前 9 年出现，也存在于原发性进展型 MS 中。健康献血者和无症状 MS 供体，无论神经丝轻链是否升高，均报告了同样高的身体和心理健康水平。基于模型的估计表明，55%的病例（95%可信区间[28%-87%]）经历了无症状期神经丝轻链水平升高。
讨论
MS 患者甚至在原发性进展型疾病中，在临床发病前 9 年内周期性地持续发生轴突损伤。这很可能代表无症状的疾病活动。一些甚至所有患者都受到这种间歇性轴突损伤的影响，这促使我们需要进一步研究无症状期与预后的关系，并将其作为治疗机会窗。
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