Cerebrospinal fluid alpha-internexin is increased in patients with multiple sclerosis and correlates strongly with neurofilament light protein.

IF 2.9 3区医学 Q2 CLINICAL NEUROLOGY

Multiple sclerosis and related disorders Pub Date : 2025-10-16 DOI:10.1016/j.msard.2025.106805

Johnsson M, Meda Fj, Lycke J, Novakova L, Rosenstein I, Johansson K, Malmeström C, Zetterberg H, Kvartsberg H, Axelsson M

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引用次数: 0

Abstract

Background: Alpha-internexin (AINX) is an intermediate filament protein predominantly found in the central nervous system (CNS) and is one of the core structural components of the neuronal cytoskeleton, along with the neurofilament triplet proteins. Because AINX is CNS-specific it has the potential to differentiate between peripheral and CNS neuroaxonal injury.

Method: We measured cerebrospinal fluid (CSF) AINX in patients with multiple sclerosis (MS) and healthy controls (HC) using an in-house AINX Simoa (Single molecule array) assay developed and validated at the Clinical Neurochemistry Laboratory at Sahlgrenska University Hospital, University of Gothenburg. The primary outcome measure was the difference in AINX between patients with MS and HCs. We also calculated correlations with age, sex, MS disease duration, magnetic resonance imaging (MRI) results, CSF biomarkers (cell count, albumin quotient, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), T-Tau, C-X-C motif ligand 13 (CXCL13)), and the influence of MS phenotype, and disease-modifying therapies.

Results: We included 34 patients with MS and 8 HCs in the analysis. AINX was detected in all samples (range: 0.16-38.4 ng/L). The median AINX was significantly increased in patients with MS (1.19 ng/L; IQR 0.69-2.34) compared with HCs (0.44 ng/L; IQR 0.36-0.51) (p < 0.001) and correlated strongly with CSF NfL (R = 0.90; p < 0.001). AINX also correlated significantly with expanded disability status scale (EDSS) score (R=-0.4; p = 0.02), number of contrast-enhancing lesions (CELs) (R = 0.6; p < 0.001), CSF cell count (R = 0.6; p < 0.001), and CSF CXCL13 (R = 0.6; p = 0.001).

Conclusion: We conclude that CSF AINX, similarly to NfL, is a marker of axonal nerve injury in patients with MS.

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多发性硬化症患者脑脊液α -连接蛋白升高，并与神经丝轻蛋白密切相关。

背景：α -间联蛋白（AINX）是一种主要存在于中枢神经系统（CNS）的中间丝蛋白，与神经丝三重体蛋白一起是神经元细胞骨架的核心结构成分之一。由于AINX是中枢特异性的，它有可能区分外周和中枢神经轴突损伤。方法：我们使用由哥德堡大学Sahlgrenska大学医院临床神经化学实验室开发并验证的内部AINX Simoa（单分子阵列）测定多发性硬化症（MS）患者和健康对照（HC）患者脑脊液（CSF） AINX。主要结局指标是MS和hc患者之间AINX的差异。我们还计算了年龄、性别、MS病程、磁共振成像（MRI）结果、脑脊液生物标志物（细胞计数、白蛋白商数、神经丝光（NfL）、胶质纤维酸性蛋白（GFAP）、T-Tau、C-X-C基序配体13 (CXCL13)）、MS表型影响和疾病修饰疗法的相关性。结果：我们纳入了34例MS和8例hc患者。所有样品中均检测到AINX（范围：0.16 ~ 38.4 ng/L）。与hc （0.44 ng/L, IQR 0.36-0.51）相比，MS患者的中位AINX显著增加（1.19 ng/L, IQR 0.69-2.34）（p < 0.001），且与CSF NfL密切相关（R = 0.90, p < 0.001）。AINX还与扩展残疾状态量表（EDSS）评分（R=-0.4; p = 0.02）、对比增强病变（CELs）数量（R= 0.6; p < 0.001）、CSF细胞计数（R= 0.6; p < 0.001）和CSF CXCL13 （R= 0.6; p = 0.001）显著相关。结论：脑脊液AINX与NfL类似，是MS患者轴突神经损伤的标志。

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

Multiple sclerosis and related disorders CLINICAL NEUROLOGY-

CiteScore

5.80

自引率

20.00%

发文量

814

审稿时长

66 days

期刊介绍： Multiple Sclerosis is an area of ever expanding research and escalating publications. Multiple Sclerosis and Related Disorders is a wide ranging international journal supported by key researchers from all neuroscience domains that focus on MS and associated disease of the central nervous system. The primary aim of this new journal is the rapid publication of high quality original research in the field. Important secondary aims will be timely updates and editorials on important scientific and clinical care advances, controversies in the field, and invited opinion articles from current thought leaders on topical issues. One section of the journal will focus on teaching, written to enhance the practice of community and academic neurologists involved in the care of MS patients. Summaries of key articles written for a lay audience will be provided as an on-line resource. A team of four chief editors is supported by leading section editors who will commission and appraise original and review articles concerning: clinical neurology, neuroimaging, neuropathology, neuroepidemiology, therapeutics, genetics / transcriptomics, experimental models, neuroimmunology, biomarkers, neuropsychology, neurorehabilitation, measurement scales, teaching, neuroethics and lay communication.