Enhancing the clinical value of serum neurofilament light chain measurement.
Enhancing the clinical value of serum neurofilament light chain measurement.
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增强血清神经丝轻链测量的临床价值。
DOI：
10.1172/jci.insight.161415
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发表时间：
2022-08-08
期刊：
影响因子：
8
通讯作者：
Bielekova, Bibiana
中科院分区：
文献类型：
--
作者：
Kosa, Peter;Masvekar, Ruturaj;Komori, Mika;Phillips, Jonathan;Ramesh, Vighnesh;Varosanec, Mihael;Sandford, Mary;Bielekova, Bibiana
血清神经丝轻链（sNFL）正成为神经轴突损伤的重要生物标志物。尽管sNFL与CSF NFL （cNFL）相关，但仍有40%至60%的方差无法解释。我们的目的是在数学上调整sNFL以增强其临床价值。我们以盲法测量了571例患者的1138例匹配CSF和血清样本的NFL。在训练队列中构建的多元线性回归（MLR）模型在独立队列中得到验证。包括年龄、血尿素氮、碱性磷酸酶、肌酐和体重在内的MLR模型改善了cNFL与sNFL的相关性（R2 = 0.57 ~ 0.67）。在多发性硬化症（MS）患者的验证队列中，协变量调整显著提高了sNFL与增强病变数量的相关性（R2 = 0.18至0.28，提高了36%）。出乎意料的是，只有sNFL，而不是cNFL，与横断面MS严重程度结果呈弱但显著相关。研究了两个不重叠的假设，我们发现sNFL与cNFL比例较高的患者有更高的脊髓（SC）损伤的临床和影像学证据，并且可能从外周轴突释放NFL进入血液，绕过CSF。sNFL包括两种轴索损伤来源，中枢和外周，后者反映SC损伤，主要驱动ms的残疾进展。美国国立卫生研究院变态反应和传染病研究所校内研究部（AI001242和AI001243）。
Serum neurofilament light chain (sNFL) is becoming an important biomarker of neuro-axonal injury. Though sNFL correlates with CSF NFL (cNFL), 40% to 60% of variance remains unexplained. We aimed to mathematically adjust sNFL to strengthen its clinical value. We measured NFL in a blinded fashion in 1138 matched CSF and serum samples from 571 patients. Multiple linear regression (MLR) models constructed in the training cohort were validated in an independent cohort. An MLR model that included age, blood urea nitrogen, alkaline phosphatase, creatinine, and weight improved correlations of cNFL with sNFL (from R2 = 0.57 to 0.67). Covariate adjustment significantly improved the correlation of sNFL with the number of contrast-enhancing lesions (from R2 = 0.18 to 0.28; 36% improvement) in the validation cohort of patients with multiple sclerosis (MS). Unexpectedly, only sNFL, but not cNFL, weakly but significantly correlated with cross-sectional MS severity outcomes. Investigating 2 nonoverlapping hypotheses, we showed that patients with proportionally higher sNFL to cNFL had higher clinical and radiological evidence of spinal cord (SC) injury and probably released NFL from peripheral axons into blood, bypassing the CSF. sNFL captures 2 sources of axonal injury, central and peripheral, the latter reflecting SC damage, which primarily drives disability progression in MS. ClinicalTrials.gov NCT00794352. Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH (AI001242 and AI001243).
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影响因子：
4.3
作者：
Masvekar R;Phillips J;Komori M;Wu T;Bielekova B
通讯作者：
Bielekova B
影响因子：
5.8
作者：
Manouchehrinia, Ali;Westerlind, Helga;Hillert, Jan
通讯作者：
Hillert, Jan
影响因子：
5.3
作者：
Kosa, Peter;Barbour, Christopher;Bielekova, Bibiana
通讯作者：
Bielekova, Bibiana
影响因子：
3.4
作者：
Thelin EP;Zeiler FA;Ercole A;Mondello S;Büki A;Bellander BM;Helmy A;Menon DK;Nelson DW
通讯作者：
Nelson DW
影响因子：
4
作者：
Kosa, Peter;Komori, Mika;Bielekova, Bibiana
通讯作者：
Bielekova, Bibiana