To examine the agreement between published reference resources for neurofilament light chain (NfL) applied to a large population of people with multiple sclerosis (MS).

Six published reference resources were used to classify NfL in participants in the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) network as elevated or normal and to derive age-specific NfL Z-scores. NfL values were classified as elevated if they exceeded the >95th percentile (i.e., Z-score >1.645) of the age-specific reference range. Furthermore, age-specific NfL Z-scores could be derived for 4 of 6 reference resources.

NfL measurements were assessed from 12,855 visits of 6,687 people with MS (median 2 samples per individual [range 1–7]). The mean ± SD age was 47.1 ± 11.7 years, 72.1% of participants were female, disease duration was 15.0 ± 10.6 years, body mass index was 28.6 ± 6.9 kg/m², and serum NfL was 12.87 ± 12.86 pg/mL. Depending on the selection of the reference resource, the proportion of NfL measurements classified as elevated varied from 3.7% to 30.9%. The kappa coefficient across the 6 reference resources used was 0.576 (95% CI 0.571–0.580) indicating moderate agreement. Spearman correlations between Z-scores derived from the various reference resources exceeded 0.90; however, concordance coefficients were lower, ranging from 0.72 to 0.89.

Interpretation of blood NfL values may vary markedly depending on the selection of the reference resource. Borderline elevated values should be interpreted with caution, and future studies should focus on standardizing NfL measurement and reporting across laboratories/platforms, better characterizing the effects of confounding/influencing factors, and defining the performance of NfL (including as part of multimodal predictive algorithms) for prediction of disease-specific outcomes.

旨在检查已发表的神经丝轻链 (NfL) 参考资源之间的一致性，该参考资源适用于大量多发性硬化症 (MS) 患者。

使用六个已发布的参考资源将多发性硬化症合作伙伴推进技术和健康解决方案 (MS PATHS) 网络参与者的 NfL 分类为升高或正常，并得出特定年龄的 NfL Z分数。如果 NfL 值超过特定年龄参考范围的>95%（即Z分数 >1.645），则将其归类为升高。此外，可以针对 6 个参考资源中的 4 个得出特定年龄的 NfL Z分数。

NfL 测量值根据 6,687 名 MS 患者的 12,855 次就诊进行评估（每人中位数 2 个样本[范围 1-7]）。平均±标准差年龄为47.1±11.7岁，72.1%的参与者为女性，病程为15.0±10.6年，体重指数为28.6±6.9 kg/m 2 ^，血清NfL为12.87±12.86 pg/mL。根据参考资源的选择，NfL 测量值被分类为升高的比例从 3.7% 到 30.9% 不等。使用的 6 个参考资源的 kappa 系数为 0.576 (95% CI 0.571–0.580)，表明中等程度的一致性。来自各种参考资源的Z分数之间的 Spearman 相关性超过 0.90；然而，一致性系数较低，范围为 0.72 至 0.89。

根据参考资源的选择，血液 NfL 值的解释可能会有显着差异。应谨慎解释边界升高值，未来的研究应侧重于跨实验室/平台标准化 NfL 测量和报告，更好地表征混杂/影响因素的影响，并定义 NfL 的性能（包括作为多模式预测算法的一部分）用于预测特定疾病的结果。