Predictors from systemic and neuro-inflammation in amyotrophic lateral sclerosis: A monocentric experience

IF 2.5 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology Pub Date : 2025-07-09 DOI:10.1016/j.jneuroim.2025.578683

Ilaria Martinelli , Cecilia Simonini , Elisabetta Zucchi , Giulia Gianferrari , Roberta Bedin , Andrea Ghezzi , Jessica Mandrioli

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引用次数: 0

Abstract

While the role of systemic and neuroinflammatory players is actually consolidated in amyotrophic lateral sclerosis (ALS) pathogenesis, a representative and reliable panel of inflammatory prognostic biomarkers is still lacking.

This retrospective study on 182 ALS patients from the Modena ALS Center, investigates biomarkers of axonal injury (neurofilaments) and microglial and astrocytic activation (SerpinA1, TREM2, CHI3L1, OPN and S100B, respectively). In a subpopulation of patients, we examined blood count-derived parameters, including the Systemic-Immune-Inflammation index (SII), Systemic Inflammation Response Index (SIRI) and Aggregate Systemic Inflammation Index (AISI). All variables were analyzed for association with clinical features in the entire cohort and then in sex- and age-based subgroups.

SerpinA1_CSF was significantly lower in females [4.43 μg/ml (IQR 2.76–6.3) vs 5.61 μg/ml (IQR 3.39–9.16),p = 0.032], while SII indexes was oppositely distributed [higher in females, 540.67 (IQR 363.05–807.24) vs 384.89 (IQR 307.5–578.52),p = 0.015]. In univariate survival analysis, without overcoming neurofilaments, SIRI (HR 1.43, 95 %CI 1.03–1.966,p = 0.03), AISI (HR 1.002, 95 %CI 1.001–1.003, p = 0.002) and SII (HR 1.001, 95 %CI 1.0003–1.001,p = 0.003) impact negatively on survival, with AISI retaining its power at multivariate analysis (HR 1.002, 95 %CI 1.0004–1.001,p = 0.012). SerpinA1_CSF levels influenced survival only for females (HR 1.042, 95 %CI 1.0065–1.078,p = 0.02), in a similar manner of SIRI (HR 1.483, 95 %CI 1.082–2.0334,p = 0.014) and SII (HR 1.00099, 95 %CI 1.0008–1.003,p = 0.001).

Our data revealed the influence of sex on survival by SerpinA1_CSF, CHI3L1_CSF and systemic biomarkers in females. However, both neurofilaments and CHI3L1_CSF outperform the other neuroinflammatory biomarkers at predicting rate of disease progression, so the prognostic meaning of these measure alone remains unconclusive, requiring larger collaborative studies.

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肌萎缩性侧索硬化症的系统性和神经炎症预测因素：单中心经验

虽然在肌萎缩性侧索硬化症（ALS）发病机制中，全身性和神经炎性因素的作用实际上得到了巩固，但一组具有代表性和可靠的炎症预后生物标志物仍然缺乏。本研究对来自Modena ALS中心的182例ALS患者进行回顾性研究，研究轴突损伤（神经丝）和小胶质细胞和星形胶质细胞激活的生物标志物（分别为SerpinA1、TREM2、CHI3L1、OPN和S100B）。在患者亚群中，我们检测了血液计数衍生的参数，包括全身免疫炎症指数（SII）、全身炎症反应指数（SIRI）和全身炎症综合指数（AISI）。在整个队列中分析所有变量与临床特征的关联，然后在基于性别和年龄的亚组中进行分析。SerpinA1CSF在女性中显著降低[4.43 μg/ml (IQR 2.76-6.3) vs 5.61 μg/ml (IQR 3.39-9.16),p = 0.032]，而SII指数在女性中呈相反分布[较高，540.67 (IQR 363.05-807.24) vs 384.89 (IQR 307.5-578.52),p = 0.015]。在单因素生存分析中，在不克服神经丝的情况下，SIRI （HR 1.43, 95% CI 1.03-1.966,p = 0.03）、AISI （HR 1.002, 95% CI 1.001 - 1.003, p = 0.002）和SII （HR 1.001, 95% CI 1.0003-1.001,p = 0.003）对生存有负面影响，AISI在多因素分析中仍保持其作用（HR 1.002, 95% CI 1.0004-1.001,p = 0.012）。SerpinA1CSF水平仅影响女性的生存率（HR 1.042, 95% CI 1.0065-1.078,p = 0.02）， SIRI （HR 1.483, 95% CI 1.082-2.0334,p = 0.014）和SII （HR 1.00099, 95% CI 1.0008-1.003,p = 0.001）的影响方式类似。我们的数据揭示了性别对女性SerpinA1CSF、CHI3L1CSF和全身生物标志物的生存的影响。然而，在预测疾病进展速度方面，神经丝和CHI3L1CSF都优于其他神经炎症生物标志物，因此单独使用这些指标的预后意义仍不确定，需要更大规模的合作研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of neuroimmunology 医学-免疫学

CiteScore

6.10

自引率

3.00%

发文量

154

审稿时长

37 days

期刊介绍： The Journal of Neuroimmunology affords a forum for the publication of works applying immunologic methodology to the furtherance of the neurological sciences. Studies on all branches of the neurosciences, particularly fundamental and applied neurobiology, neurology, neuropathology, neurochemistry, neurovirology, neuroendocrinology, neuromuscular research, neuropharmacology and psychology, which involve either immunologic methodology (e.g. immunocytochemistry) or fundamental immunology (e.g. antibody and lymphocyte assays), are considered for publication.