Department of Neurosciences, Azienda Ospedaliero Universitaria di Modena, Modena, Italy.
Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy.
Eur J Neurol. 2024 Jan;31(1):e16054. doi: 10.1111/ene.16054. Epub 2023 Sep 7.
SerpinA1, a serine protease inhibitor, is involved in the modulation of microglial-mediated inflammation in neurodegenerative diseases. We explored SerpinA1 levels in cerebrospinal fluid (CSF) and serum of amyotrophic lateral sclerosis (ALS) patients to understand its potential role in the pathogenesis of the disease.
SerpinA1, neurofilament light (NfL) and heavy (NfH) chain, and chitinase-3-like protein-1 (CHI3L1) were determined in CSF and serum of ALS patients (n = 110) and healthy controls (n = 10) (automated next-generation ELISA), and correlated with clinical parameters, after identifying three classes of progressors (fast, intermediate, slow). Biomarker levels were analyzed for diagnostic power and association with progression and survival.
SerpinA1 was significantly decreased in ALS (median: 1032 μg/mL) compared with controls (1343 μg/mL) (p = 0.02). SerpinA1 was elevated only in fast progressors (8.6 μg/mL) compared with slow (4.43 μg/mL, p = 0.01) and intermediate (4.42 μg/mL, p = 0.03) progressors. Moreover, SerpinA1 correlated with neurofilament and CHI3L1 levels in CSF. Contrarily to SerpinA1 , neurofilament and CHI3L1 concentrations in CSF correlated with measures of disease progression in ALS, while SerpinA1 mildly related with time to generalization (rho = 0.20, p = 0.04). In multivariate analysis, the ratio between serum and CSF SerpinA1 (SerpinA1 ratio) and NfH were independently associated with survival.
Higher SerpinA1 levels are found in fast progressors, suggesting SerpinA1 is a component of the neuroinflammatory mechanisms acting upon fast-progressing forms of ALS. Both neurofilaments or CHI3L1 levels outperformed SerpinA1 at predicting disease progression rate in our cohort, and so the prognostic value of SerpinA1 alone as a measure remains inconclusive.
丝氨酸蛋白酶抑制剂 SerpinA1 参与神经退行性疾病中小胶质细胞介导的炎症调节。我们研究了肌萎缩侧索硬化症（ALS）患者脑脊液（CSF）和血清中的 SerpinA1 水平，以了解其在疾病发病机制中的潜在作用。
使用自动化下一代 ELISA 法测定了 110 例 ALS 患者和 10 例健康对照者的 CSF 和血清中的 SerpinA1、神经丝轻链（NfL）和重链（NfH）以及几丁质酶 3 样蛋白 1（CHI3L1），并与临床参数相关联。在确定了三类进展者（快速、中间和缓慢）后。分析了生物标志物水平的诊断能力以及与进展和生存的关系。
与对照组（1343μg/ml）相比，ALS 患者的 SerpinA1 水平显著降低（中位数：1032μg/ml）（p=0.02）。与慢进展者（4.43μg/ml，p=0.03）和中间进展者（4.42μg/ml，p=0.03）相比，快速进展者的 SerpinA1 水平显著升高（8.6μg/ml）。此外，SerpinA1 与 CSF 中的神经丝和 CHI3L1 水平相关。与 SerpinA1 相反，CSF 中神经丝和 CHI3L1 的浓度与 ALS 患者的疾病进展测量值相关，而 SerpinA1 与泛化时间轻度相关（rho=0.20，p=0.04）。在多变量分析中，血清和 CSF 中 SerpinA1 的比值（SerpinA1 比值）和 NfH 与生存独立相关。
快速进展者中 SerpinA1 水平较高，提示 SerpinA1 是作用于 ALS 快速进展形式的神经炎症机制的组成部分。在我们的队列中，神经丝或 CHI3L1 水平在预测疾病进展率方面优于 SerpinA1，因此 SerpinA1 作为单一指标的预后价值仍不确定。
