Cerebrospinal fluid biomarkers associated with neurofilament light levels: A study in HIV disease

IF 2.9 4区医学 Q3 IMMUNOLOGY

Journal of neuroimmunology Pub Date : 2025-01-06 DOI:10.1016/j.jneuroim.2025.578521

Enrico Ripamonti , Magnus Gisslén , Lars Hagberg , Pradeepthi Bathala , Shraddha Kale , Martin Stengelin , George Sigal , Jacob Wohlstadter , Henrik Zetterberg , Richard Price

{"title":"Cerebrospinal fluid biomarkers associated with neurofilament light levels: A study in HIV disease","authors":"Enrico Ripamonti , Magnus Gisslén , Lars Hagberg , Pradeepthi Bathala , Shraddha Kale , Martin Stengelin , George Sigal , Jacob Wohlstadter , Henrik Zetterberg , Richard Price","doi":"10.1016/j.jneuroim.2025.578521","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>A retrospective study was conducted in people with HIV (PWH) to explore potential cerebrospinal fluid (CSF) biomarkers linked to CSF neurofilament light levels (NfL), indicative of neuronal injury.</div></div><div><h3>Methods</h3><div>A sample of 168 participants was tested, including 43 HIV-negative controls and PWH who were classified into subgroups based on HIV and treatment status. Twenty CSF protein biomarkers were analyzed for their association with CSF NfL concentrations using a linear regression forward selection strategy, adjusted for age and sex. Regression trees were utilized to visualize feature relationships.</div></div><div><h3>Results</h3><div>Age-adjusted average concentrations of CSF NfL ranged from 427 pg/mL (SD = 190) in HIV- participants to 6456 pg/mL (SD = 46,024) in participants with HIV-associated dementia. Significant associations were found between specific biomarkers and CSF NfL levels in different participant subgroups. Noteworthy findings included correlations between CSF t-tau, CSF MCP-1, CSF TNF-α, and albumin ratio with CSF NfL levels in untreated PWH, and CSF IL-21 with CSF NfL in treated, virally suppressed PWH. Association between age and CSF NfL concentrations was a general finding.</div></div><div><h3>Conclusion</h3><div>We identified specific CSF biomarkers, including CSF t-tau protein, CSF MCP-1, and CSF TNF-α that associated with CSF NfL concentrations in untreated PWH and CSF IL-21 that associated with CSF NfL in PWH with effective treatment, shedding light on neuroinflammatory processes which may underlie HIV-related neuronal injury and the impact of antiviral therapy. Further investigations are needed to validate if elevated CSF IL-21 concentrations persist during long-term treatment, and if particular drug combinations are optimal for decreasing inflammatory latency.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"400 ","pages":"Article 578521"},"PeriodicalIF":2.9000,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of neuroimmunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0165572825000013","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

A retrospective study was conducted in people with HIV (PWH) to explore potential cerebrospinal fluid (CSF) biomarkers linked to CSF neurofilament light levels (NfL), indicative of neuronal injury.

Methods

A sample of 168 participants was tested, including 43 HIV-negative controls and PWH who were classified into subgroups based on HIV and treatment status. Twenty CSF protein biomarkers were analyzed for their association with CSF NfL concentrations using a linear regression forward selection strategy, adjusted for age and sex. Regression trees were utilized to visualize feature relationships.

Results

Age-adjusted average concentrations of CSF NfL ranged from 427 pg/mL (SD = 190) in HIV- participants to 6456 pg/mL (SD = 46,024) in participants with HIV-associated dementia. Significant associations were found between specific biomarkers and CSF NfL levels in different participant subgroups. Noteworthy findings included correlations between CSF t-tau, CSF MCP-1, CSF TNF-α, and albumin ratio with CSF NfL levels in untreated PWH, and CSF IL-21 with CSF NfL in treated, virally suppressed PWH. Association between age and CSF NfL concentrations was a general finding.

Conclusion

We identified specific CSF biomarkers, including CSF t-tau protein, CSF MCP-1, and CSF TNF-α that associated with CSF NfL concentrations in untreated PWH and CSF IL-21 that associated with CSF NfL in PWH with effective treatment, shedding light on neuroinflammatory processes which may underlie HIV-related neuronal injury and the impact of antiviral therapy. Further investigations are needed to validate if elevated CSF IL-21 concentrations persist during long-term treatment, and if particular drug combinations are optimal for decreasing inflammatory latency.

查看原文本刊更多论文

与神经丝光水平相关的脑脊液生物标志物：HIV疾病的一项研究

背景：在HIV感染者（PWH）中进行了一项回顾性研究，以探索与CSF神经丝光水平（NfL）相关的潜在脑脊液（CSF）生物标志物，这表明神经元损伤。方法对168名参与者进行检测，其中包括43名HIV阴性对照和PWH，他们根据HIV和治疗情况分为亚组。使用线性回归正向选择策略分析了20种脑脊液蛋白生物标志物与脑脊液NfL浓度的相关性，并根据年龄和性别进行了调整。利用回归树对特征关系进行可视化。结果：经年龄调整后的CSF NfL平均浓度范围从HIV参与者的427 pg/mL （SD = 190）到HIV相关痴呆参与者的6456 pg/mL （SD = 46024）。在不同参与者亚组中，特定生物标志物与CSF NfL水平之间存在显著关联。值得注意的发现包括未经治疗的PWH患者CSF t-tau、CSF MCP-1、CSF TNF-α和白蛋白比值与CSF NfL水平的相关性，以及经病毒抑制的PWH患者CSF IL-21与CSF NfL水平的相关性。年龄与脑脊液NfL浓度之间的关系是一个普遍的发现。我们鉴定了特异性CSF生物标志物，包括CSF t-tau蛋白、CSF MCP-1和CSF TNF-α，它们与未治疗PWH中CSF NfL浓度相关，CSF IL-21与有效治疗PWH中CSF NfL浓度相关，揭示了可能是hiv相关神经元损伤基础的神经炎症过程和抗病毒治疗的影响。需要进一步的研究来验证脑脊液IL-21浓度升高是否在长期治疗中持续存在，以及特定的药物组合是否最适合减少炎症潜伏期。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

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.