Department of Neurology, Seoul National University Hospital, Seoul, Republic of Korea.
Department of Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Ann Clin Transl Neurol. 2024 Jul;11(7):1809-1818. doi: 10.1002/acn3.52087. Epub 2024 May 22.
In comparison with amyotrophic lateral sclerosis (ALS), the contribution of neuroinflammation in spinobulbar muscular atrophy (SBMA) has been less explored. We investigated the role of neuroinflammation in the pathogenesis of ALS and SBMA by analyzing systemic inflammatory markers and osteopontin (Spp1).
This study involved 105 ALS, 77 SBMA, and 55 healthy controls. We measured their systemic inflammatory markers, serum Spp1, and cytokine levels (interferon-γ, interleukin [IL]-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α, and IL-17A), investigated correlations between Spp1 levels and clinical features, and evaluated ALS survival rates according to Spp1 levels.
In the ALS group, systemic inflammatory markers were significantly higher than in the control and SBMA groups. Spp1 levels were observed to be higher in ALS patients, but the difference was not statistically significant among the study groups. Cytokine profiles were comparable. In ALS, higher Spp1 levels were correlated with lower ALS Functional Rating Scale-Revised (ALSFRS-R) scores (r = -0.25, p = 0.02) and faster disease progression rate (r = 0.37, p < 0.001). After adjusting for other prognostic indicators, high Spp1 levels were independently associated with shorter survival in ALS patients (hazard ratio 13.65, 95% confidence interval 2.57-72.53, p < 0.01).
Neuroinflammation does not appear to be a primary contributor to the pathogenesis of SBMA. Serum Spp1 levels may serve as a reliable biomarker for disease progression and prognosis in ALS. These findings expand our understanding of these two distinct motor neuron disorders and offer a potential biomarker for future studies.
与肌萎缩侧索硬化症（ALS）相比，神经炎症在延髓脊髓性肌萎缩症（SBMA）中的作用研究较少。我们通过分析系统炎症标志物和骨桥蛋白（Spp1）来研究神经炎症在 ALS 和 SBMA 发病机制中的作用。
本研究纳入了 105 例 ALS 患者、77 例 SBMA 患者和 55 名健康对照者。我们测量了他们的系统炎症标志物、血清 Spp1 和细胞因子水平（干扰素-γ、白细胞介素[IL]-1β、IL-6、IL-8、IL-10、肿瘤坏死因子-α和 IL-17A），研究了 Spp1 水平与临床特征的相关性，并根据 Spp1 水平评估 ALS 患者的生存率。
在 ALS 组中，系统炎症标志物明显高于对照组和 SBMA 组。ALS 患者的 Spp1 水平较高，但组间差异无统计学意义。细胞因子谱相似。在 ALS 患者中，较高的 Spp1 水平与较低的 ALS 功能评定量表修订版（ALSFRS-R）评分（r=-0.25，p=0.02）和更快的疾病进展速度（r=0.37，p<0.001）相关。在调整其他预后指标后，高 Spp1 水平与 ALS 患者的生存期较短独立相关（风险比 13.65，95%置信区间 2.57-72.53，p<0.01）。
神经炎症似乎不是 SBMA 发病机制的主要原因。血清 Spp1 水平可能是 ALS 疾病进展和预后的可靠生物标志物。这些发现扩展了我们对这两种不同的运动神经元疾病的认识，并为未来的研究提供了一个潜在的生物标志物。
