From the Neuroimmunology Unit (L.C.-N., S.G.-P., J.C.-V., V.L., R.G., S.C., C.A., F.P.-M., B.C.), Polytechnic and University Hospital La Fe; Neurology Department (L.S.T.), University Hospital Dr Peset, Valencia, Spain; and Department of Neuroimmunology (H.L.), Center for Brain Research, Vienna, Austria.
Neurol Neuroimmunol Neuroinflamm. 2021 Mar 3;8(3). doi: 10.1212/NXI.0000000000000972. Print 2021 May 4.
Neurofilament light protein (NfL) and chitinase 3-like 1 (CHI3L1) are biomarkers for acute neuroaxonal damage and local inflammation, respectively. Thus, we set out to evaluate how these biomarkers were associated with clinical features of demyelinating diseases in parallel with the expression in brain autopsies from patients with similar disease stages, assuming their comparability.
NfL and CHI3L1 in CSF and serum CHI3L1 were assessed retrospectively in a cross-sectional cohort of controls (n = 17) and patients diagnosed with MS (n = 224), relapsing (n = 163) or progressive (n = 61); neuromyelitis optica (NMO, n = 7); and acute disseminated encephalomyelitis (ADEM, n = 15). Inflammatory activity was evaluated at the time of sampling, and CSF biomarker levels were related to the degree of inflammation in 22 brain autopsy tissues.
During a clinical attack, the CSF NfL increased in MS, NMO, and ADEM, whereas CHI3L1 was only elevated in patients with NMO and ADEM and in outlier MS patients with extensive radiologic activity. Outside relapses, CHI3L1 levels only remained elevated in patients with progressive MS. CHI3L1 was detected in macrophages and astrocytes, predominantly in areas of active demyelination, and its expression by astrocytes in chronic lesions was independent of lymphocyte infiltrates and associated with active neurodegeneration.
Both CSF NfL and CHI3L1 augment during acute inflammation in demyelinating diseases. In MS, CHI3L1 may be associated with low-grade nonlymphocytic inflammation and active neurodegeneration and therefore linked to progressive disease.
This study provides Class III evidence that CSF NfL and CHI3L1 levels increase in inflammatory brain diseases during acute inflammation.
神经丝轻链蛋白（NfL）和几丁质酶 3 样蛋白 1（CHI3L1）分别是急性神经轴索损伤和局部炎症的生物标志物。因此，我们着手评估这些生物标志物与脱髓鞘疾病的临床特征之间的关联，并与具有相似疾病阶段的脑尸检标本中的表达进行平行比较，假设它们具有可比性。
我们回顾性评估了一个对照组（n=17）和多发性硬化症（MS）患者（n=224，复发型 n=163，进展型 n=61）、视神经脊髓炎（NMO，n=7）和急性播散性脑脊髓炎（ADEM，n=15）患者的脑脊液（CSF）NfL 和血清 CHI3L1，同时评估了采样时的炎症活动，并将 CSF 生物标志物水平与 22 例脑尸检组织中的炎症程度进行了关联。
在临床发作期间，MS、NMO 和 ADEM 的 CSF NfL 增加，而 CHI3L1 仅在 NMO 和 ADEM 患者以及具有广泛影像学活动的 MS 患者中升高。在复发期之外，进展型 MS 患者的 CHI3L1 水平仍持续升高。CHI3L1 在巨噬细胞和星形胶质细胞中被检测到，主要存在于活跃脱髓鞘区，其在慢性病变中的表达与淋巴细胞浸润无关，且与活跃的神经退行性变相关。
CSF NfL 和 CHI3L1 均在脱髓鞘疾病的急性炎症期间增加。在 MS 中，CHI3L1 可能与低度非淋巴细胞炎症和活跃的神经退行性变有关，因此与进行性疾病有关。
本研究提供了 III 级证据，表明 CSF NfL 和 CHI3L1 水平在炎症性脑疾病的急性炎症期间升高。
